M. S. Cairo, J. Hochberg, K. Klose, J. Basso, A. Gardenswartz, A. Flower, S. Braniecki, L. Harrison
<p><b>Introduction:</b> Despite excellent survival outcomes, significant chronic health conditions occur among pediatric, adolescent, and young adult classical Hodgkin lymphoma (cHL) survivors as a result of current chemotherapy and radiation regimens. Targeting both the tumor microenvironment as well as tumor-specific antigens have been proven to be effective and safe treatments for cHL patients. Here we report on our Hodgkin Lymphoma immunotherapy approach over the past 13 yrs. We have combined the use of the antibody-drug conjugate brentuximab vedotin (Bv) to target reed-sternberg cells along with the anti-CD20 antibody rituximab (RTX) and checkpoint inhibitor nivolumab (N) targeting the immune microenvironment added to risk-adapted chemotherapy in newly diagnosed CAYA cHL patients. This chemoimmunotherapy approach may allow for anthracycline dose reduction and radiation sparing in intermediate and high risk patients.</p><p><b>Methods:</b> All patients received 2 cycles of Bv, doxorubicin, vinblastine, dacarbazine, and RTX (Bv-AVD-R). Early response utilizing FDG-PET scan was performed following 2 cycles of therapy (PET2) with PET2 negativity defined as Deauville score of 1, 2 or 3. Rapid early responders (RER) or slow early responders (SER) received an additional 2 to 6 cycles of treatment based on risk assignment and early response. After our initial protocol completed enrollment, subsequent patients were enrolled on our follow up study evaluating the addition of nivolumab beginning with cycle 3 therapy without further anthracycline (Bv-NVD-R). This limited the total anthracycline dose to 100 mg/m<sup>2</sup> per patient. Radiation therapy initially was planned for high risk patients with SER and subsequently on our current study only for patients not achieving metabolic CR by FDG-PET at the completion of all therapy.</p><p><b>Results:</b> A total of 48 patients have completed therapy with a median age of 17 years (4–23 years), Thirty four patients received Bv-AVD-R for all cycles and 14 patients have been enrolled on our follow up study receiving Bv-AVD-R followed by Bv-NVD-R. All 48 patients achieved a complete response to therapy for a CR rate of 100%. Early PET2 negativity was achieved in 42 patients (87.5%). Due to excellent rapid response, only four patients have required radiation therapy. The EFS and OS is 100% with a median follow up time of > 90 months (range 4–159 months) (Fig 1). Accrual is ongoing for our current trial. We have completed the nivolumab saftey run in. There have been no unexpected adverse events related to therapy and no dose limiting toxicities with the addition of nivolumab to our immunochemotherapy backbone.</p><p><b>Conclusions:</b> The addition of immunotherapy to a reduced chemotherapy backbone is safe, effective and well tolerated. Targeting the HRS cell as well as the tumor microenvironment and PD1/PD-L1 axis is a promising approach in CAYA with cHL and may allow for reduction in anthracycline and radia
{"title":"TARGETED IMMUNOTHERAPY IN CHILDREN, ADOLESCENTS, AND YOUNG ADULTS WITH NEWLY DIAGNOSED CLASSICAL HODGKIN LYMPHOMA, A SINGLE CENTER EXPERIENCE","authors":"M. S. Cairo, J. Hochberg, K. Klose, J. Basso, A. Gardenswartz, A. Flower, S. Braniecki, L. Harrison","doi":"10.1002/hon.70093_34","DOIUrl":"https://doi.org/10.1002/hon.70093_34","url":null,"abstract":"<p><b>Introduction:</b> Despite excellent survival outcomes, significant chronic health conditions occur among pediatric, adolescent, and young adult classical Hodgkin lymphoma (cHL) survivors as a result of current chemotherapy and radiation regimens. Targeting both the tumor microenvironment as well as tumor-specific antigens have been proven to be effective and safe treatments for cHL patients. Here we report on our Hodgkin Lymphoma immunotherapy approach over the past 13 yrs. We have combined the use of the antibody-drug conjugate brentuximab vedotin (Bv) to target reed-sternberg cells along with the anti-CD20 antibody rituximab (RTX) and checkpoint inhibitor nivolumab (N) targeting the immune microenvironment added to risk-adapted chemotherapy in newly diagnosed CAYA cHL patients. This chemoimmunotherapy approach may allow for anthracycline dose reduction and radiation sparing in intermediate and high risk patients.</p><p><b>Methods:</b> All patients received 2 cycles of Bv, doxorubicin, vinblastine, dacarbazine, and RTX (Bv-AVD-R). Early response utilizing FDG-PET scan was performed following 2 cycles of therapy (PET2) with PET2 negativity defined as Deauville score of 1, 2 or 3. Rapid early responders (RER) or slow early responders (SER) received an additional 2 to 6 cycles of treatment based on risk assignment and early response. After our initial protocol completed enrollment, subsequent patients were enrolled on our follow up study evaluating the addition of nivolumab beginning with cycle 3 therapy without further anthracycline (Bv-NVD-R). This limited the total anthracycline dose to 100 mg/m<sup>2</sup> per patient. Radiation therapy initially was planned for high risk patients with SER and subsequently on our current study only for patients not achieving metabolic CR by FDG-PET at the completion of all therapy.</p><p><b>Results:</b> A total of 48 patients have completed therapy with a median age of 17 years (4–23 years), Thirty four patients received Bv-AVD-R for all cycles and 14 patients have been enrolled on our follow up study receiving Bv-AVD-R followed by Bv-NVD-R. All 48 patients achieved a complete response to therapy for a CR rate of 100%. Early PET2 negativity was achieved in 42 patients (87.5%). Due to excellent rapid response, only four patients have required radiation therapy. The EFS and OS is 100% with a median follow up time of > 90 months (range 4–159 months) (Fig 1). Accrual is ongoing for our current trial. We have completed the nivolumab saftey run in. There have been no unexpected adverse events related to therapy and no dose limiting toxicities with the addition of nivolumab to our immunochemotherapy backbone.</p><p><b>Conclusions:</b> The addition of immunotherapy to a reduced chemotherapy backbone is safe, effective and well tolerated. Targeting the HRS cell as well as the tumor microenvironment and PD1/PD-L1 axis is a promising approach in CAYA with cHL and may allow for reduction in anthracycline and radia","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70093_34","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Rivas-Delgado, H. S. Raman, M. Kabat, N. Glaubach, M. Corona, E. Luttwak, L. Falchi, J. Lue, M. Scordo, A. D. Zelenetz, M. Perales, G. L. Shah, J. H. Park, S. Ringelstein-Harlev, O. Beyar-Katz, L. A. Leslie, A. Ip, P. Armand, C. A. Jacobson, M. L. Palomba, R. Shouval, R. W. Merryman, G. Salles
<p>H. S. Raman equally contributing author.</p><p><b>Introduction:</b> CD19-directed CAR T-cell therapy (CAR-T) has demonstrated outstanding therapeutic activity in patients (pts) with refractory/relapsed (R/R) follicular lymphoma (FL). However, data regarding histological features, treatment patterns, and outcomes of pts with disease progression (POD) following CD19 CAR-T therapy for R/R are poorly understood.</p><p><b>Methods:</b> Characteristics of 101 pts receiving CAR-T for FL were collected across 4 international centers. Pts with FL grade 3B or any prior history of histological transformation were excluded.</p><p><b>Results:</b> We identified 25 pts (24.8%) who experienced POD after CAR-T. Median age at infusion was 62 years (range 34–79). Pre CAR-T FL grade was 1–2 in 76% of the pts, grade 3A in 12%, and unavailable in 12%. Median prior therapy lines were 3 (range 2–7). Administered products were axicabtagene ciloleucel (84%), tisagenlecleucel (12%), and lisocabtagene maraleucel (4%), predominantly as SOC (96%). High-risk features before CAR-T were common: 40% had experienced POD24, 68% were refractory to their last therapy, including 32% with primary refractory disease. Among pts with post-CAR-T POD, the best post-infusion response was CR in 56%, PR in 20%, and stable or progressive disease in 24%. The median time from CAR-T infusion to POD was 8.9 months (IQR 3–15).</p><p>Following POD, 20 pts received systemic therapy (median 1 line, range 1–7), 3 remain on active surveillance, 1 received palliative care, and 1 was lost to follow-up. The ORR after initial post-POD therapy was 72% among evaluable pts. Administered therapies included CD3×CD20 bispecific antibodies (BsAbs) (<i>n</i> = 10; 8 evaluable, ORR 88%, CR 63%), chemoimmunotherapy (<i>n</i> = 6, ORR 83%, CR 50%), tafasitamab-based combinations (lenalidomide, <i>n</i> = 1; tazemetostat, <i>n</i> = 1; no response), lenalidomide + obinutuzumab (<i>n</i> = 1; no response), and investigational agent (<i>n</i> = 1; ORR 100%). Three pts underwent allogeneic SCT as consolidation and are still in remission.</p><p>In 18 pts with post-CAR-T POD histologic documentation, 3 had transformed FL to diffuse large B-cell lymphoma, 1 had FL grade 3B, and 14 had relapsed FL grade 1–3A. CD19-negative disease was found in 1 pt, while 5 (28%) had CD20-negative disease (3 pre-CAR-T exposed to CD3xCD20 BsAb).</p><p>Median follow-up for the entire cohort and from POD was 24 and 16 months, respectively. Median progression-free survival post CAR-T POD was 19 months (95% CI: 10–28) with an estimated 1-year PFS of 68% (95% CI: 50–91). During follow-up, 5 pts (18%) died, all due to disease progression. Median overall survival from POD was not reached, with an estimated 1-y OS of 86% (95% CI: 73–100) (Figure).</p><p><b>Conclusions:</b> To our knowledge, this represents the largest cohort of FL pts with POD post-CAR-T. BsAbs showed promise in this setting, but longer follow-up is needed for durability assessment.
{"title":"HISTOLOGICAL CHARACTERISTICS, TREATMENT PATTERNS, AND OUTCOMES FOLLOWING DISEASE PROGRESSION AFTER CAR-T THERAPY IN RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA","authors":"A. Rivas-Delgado, H. S. Raman, M. Kabat, N. Glaubach, M. Corona, E. Luttwak, L. Falchi, J. Lue, M. Scordo, A. D. Zelenetz, M. Perales, G. L. Shah, J. H. Park, S. Ringelstein-Harlev, O. Beyar-Katz, L. A. Leslie, A. Ip, P. Armand, C. A. Jacobson, M. L. Palomba, R. Shouval, R. W. Merryman, G. Salles","doi":"10.1002/hon.70094_250","DOIUrl":"https://doi.org/10.1002/hon.70094_250","url":null,"abstract":"<p>H. S. Raman equally contributing author.</p><p><b>Introduction:</b> CD19-directed CAR T-cell therapy (CAR-T) has demonstrated outstanding therapeutic activity in patients (pts) with refractory/relapsed (R/R) follicular lymphoma (FL). However, data regarding histological features, treatment patterns, and outcomes of pts with disease progression (POD) following CD19 CAR-T therapy for R/R are poorly understood.</p><p><b>Methods:</b> Characteristics of 101 pts receiving CAR-T for FL were collected across 4 international centers. Pts with FL grade 3B or any prior history of histological transformation were excluded.</p><p><b>Results:</b> We identified 25 pts (24.8%) who experienced POD after CAR-T. Median age at infusion was 62 years (range 34–79). Pre CAR-T FL grade was 1–2 in 76% of the pts, grade 3A in 12%, and unavailable in 12%. Median prior therapy lines were 3 (range 2–7). Administered products were axicabtagene ciloleucel (84%), tisagenlecleucel (12%), and lisocabtagene maraleucel (4%), predominantly as SOC (96%). High-risk features before CAR-T were common: 40% had experienced POD24, 68% were refractory to their last therapy, including 32% with primary refractory disease. Among pts with post-CAR-T POD, the best post-infusion response was CR in 56%, PR in 20%, and stable or progressive disease in 24%. The median time from CAR-T infusion to POD was 8.9 months (IQR 3–15).</p><p>Following POD, 20 pts received systemic therapy (median 1 line, range 1–7), 3 remain on active surveillance, 1 received palliative care, and 1 was lost to follow-up. The ORR after initial post-POD therapy was 72% among evaluable pts. Administered therapies included CD3×CD20 bispecific antibodies (BsAbs) (<i>n</i> = 10; 8 evaluable, ORR 88%, CR 63%), chemoimmunotherapy (<i>n</i> = 6, ORR 83%, CR 50%), tafasitamab-based combinations (lenalidomide, <i>n</i> = 1; tazemetostat, <i>n</i> = 1; no response), lenalidomide + obinutuzumab (<i>n</i> = 1; no response), and investigational agent (<i>n</i> = 1; ORR 100%). Three pts underwent allogeneic SCT as consolidation and are still in remission.</p><p>In 18 pts with post-CAR-T POD histologic documentation, 3 had transformed FL to diffuse large B-cell lymphoma, 1 had FL grade 3B, and 14 had relapsed FL grade 1–3A. CD19-negative disease was found in 1 pt, while 5 (28%) had CD20-negative disease (3 pre-CAR-T exposed to CD3xCD20 BsAb).</p><p>Median follow-up for the entire cohort and from POD was 24 and 16 months, respectively. Median progression-free survival post CAR-T POD was 19 months (95% CI: 10–28) with an estimated 1-year PFS of 68% (95% CI: 50–91). During follow-up, 5 pts (18%) died, all due to disease progression. Median overall survival from POD was not reached, with an estimated 1-y OS of 86% (95% CI: 73–100) (Figure).</p><p><b>Conclusions:</b> To our knowledge, this represents the largest cohort of FL pts with POD post-CAR-T. BsAbs showed promise in this setting, but longer follow-up is needed for durability assessment. ","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70094_250","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Brocard, D. Roos-Weil, L. Kanagaratnam, L. Bussot, B. Papoular, C. Tomowiak, S. Chevreux, G. Crochet, T. Vaugeois, E. Toussaint, A. Quinquenel, P. Kapoor, E. Durot
<p><b>Introduction:</b> Patients with histological transformation (HT) of Waldenström macroglobulinemia (WM) who relapse or are refractory (R/R) have a poor prognosis, especially those who are not eligible or relapsing after high-dose chemotherapy with autologous stem cell transplant (ASCT) and/or chimeric antigen receptor (CAR) T-cell therapy. CD3xCD20 bispecific monoclonal antibodies (BsAb) (epcoritamab, glofitamab) provide overall and complete responses of around 60% and 40%, respectively, in R/R diffuse large-cell B lymphomas (DLBCL). However, these therapies have not been evaluated in HT of WM. The aim of this study was to evaluate the efficacy and safety of CD3xCD20 BsAb in patients with R/R transformed WM.</p><p><b>Methods:</b> We retrospectively identified patients with biopsy-proven transformed WM/lymphoplasmacytic lymphoma treated with epcoritamab or glofitamab in FILO/LYSA centers and an American center. The primary endpoint was best overall response rate (ORR). Secondary endpoints were best complete response rate (CRR), progression free-survival (PFS), overall survival (OS) and safety. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded according to the ASTCT 2019 criteria. Hematological toxicity and infections were graded according to NCI CTCAE (version 5.0).</p><p><b>Results:</b> Between February 2023 and July 2024, 12 patients with R/R transformed WM were treated with BsAb (6 glofitamab and 6 epcoritamab). Median age at WM diagnosis was 72 years (range 43–83). Patients received a median of 1 prior line of treatment (range, 0–6) for WM, including 4 treated with a BTK inhibitor (2 with ibrutinib, 1 with zanubritinib and 1 received both successively). 4 patients had concurrent diagnosis of WM and DLBCL. For the others, the median time from WM to HT was 5.3 years (range, 0.4–12.8) and 15 months (range, 1–48) from HT diagnosis to BsAb. Patients had received a median of 2 prior lines (range, 1–5) for HT. Five patients were previously treated with CAR T-cell, including 2 with prior ASCT. At the time of BsAb, 75% of patients were refractory to the last treatment, and 67% to at least 2 consecutive lines. The median age was 80 years (range, 45–86). Patient treated with glofitamab had received a median of 9 cycles (6–12) and those treated with epcoritamab a median of 3 cycles (2–6). Best ORR was 92% and best CRR was 42%. CRS occurred in 10 patients (83%, with only 1 grade 3) and ICANS in 2 patients (17%, no grade 3–4). Seven patients (58%) presented infections, including 4 grade 3. After a median follow-up of 9.4 months (95% CI: 4–23), the 6-months PFS and OS were 57% (95% CI: 34%–94%) and 75% (95% CI: 54%–100%), respectively. Five deaths were reported, 3 due to disease progression and 2 from infection.</p><p><b>Conclusion:</b> This study shows an interesting efficacy of CD3xCD20 BsAb in R/R transformed WM in a population of elderly and heavily pre-treated patients, without unexpected
{"title":"CD3XCD20 BISPECIFIC ANTIBODIES IN TRANSFORMED WALDENSTRÖM MACROGLOBULINEMIA/LYMPHOPLASMACYTIC LYMPHOMA","authors":"M. Brocard, D. Roos-Weil, L. Kanagaratnam, L. Bussot, B. Papoular, C. Tomowiak, S. Chevreux, G. Crochet, T. Vaugeois, E. Toussaint, A. Quinquenel, P. Kapoor, E. Durot","doi":"10.1002/hon.70094_264","DOIUrl":"https://doi.org/10.1002/hon.70094_264","url":null,"abstract":"<p><b>Introduction:</b> Patients with histological transformation (HT) of Waldenström macroglobulinemia (WM) who relapse or are refractory (R/R) have a poor prognosis, especially those who are not eligible or relapsing after high-dose chemotherapy with autologous stem cell transplant (ASCT) and/or chimeric antigen receptor (CAR) T-cell therapy. CD3xCD20 bispecific monoclonal antibodies (BsAb) (epcoritamab, glofitamab) provide overall and complete responses of around 60% and 40%, respectively, in R/R diffuse large-cell B lymphomas (DLBCL). However, these therapies have not been evaluated in HT of WM. The aim of this study was to evaluate the efficacy and safety of CD3xCD20 BsAb in patients with R/R transformed WM.</p><p><b>Methods:</b> We retrospectively identified patients with biopsy-proven transformed WM/lymphoplasmacytic lymphoma treated with epcoritamab or glofitamab in FILO/LYSA centers and an American center. The primary endpoint was best overall response rate (ORR). Secondary endpoints were best complete response rate (CRR), progression free-survival (PFS), overall survival (OS) and safety. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded according to the ASTCT 2019 criteria. Hematological toxicity and infections were graded according to NCI CTCAE (version 5.0).</p><p><b>Results:</b> Between February 2023 and July 2024, 12 patients with R/R transformed WM were treated with BsAb (6 glofitamab and 6 epcoritamab). Median age at WM diagnosis was 72 years (range 43–83). Patients received a median of 1 prior line of treatment (range, 0–6) for WM, including 4 treated with a BTK inhibitor (2 with ibrutinib, 1 with zanubritinib and 1 received both successively). 4 patients had concurrent diagnosis of WM and DLBCL. For the others, the median time from WM to HT was 5.3 years (range, 0.4–12.8) and 15 months (range, 1–48) from HT diagnosis to BsAb. Patients had received a median of 2 prior lines (range, 1–5) for HT. Five patients were previously treated with CAR T-cell, including 2 with prior ASCT. At the time of BsAb, 75% of patients were refractory to the last treatment, and 67% to at least 2 consecutive lines. The median age was 80 years (range, 45–86). Patient treated with glofitamab had received a median of 9 cycles (6–12) and those treated with epcoritamab a median of 3 cycles (2–6). Best ORR was 92% and best CRR was 42%. CRS occurred in 10 patients (83%, with only 1 grade 3) and ICANS in 2 patients (17%, no grade 3–4). Seven patients (58%) presented infections, including 4 grade 3. After a median follow-up of 9.4 months (95% CI: 4–23), the 6-months PFS and OS were 57% (95% CI: 34%–94%) and 75% (95% CI: 54%–100%), respectively. Five deaths were reported, 3 due to disease progression and 2 from infection.</p><p><b>Conclusion:</b> This study shows an interesting efficacy of CD3xCD20 BsAb in R/R transformed WM in a population of elderly and heavily pre-treated patients, without unexpected","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70094_264","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Deshane, J. Yahalom, N. A. Wijetunga, A. Kumar, B. Fregonese, A. Zelenetz, G. Salles, B. S. Imber
<p><b>Introduction:</b> The role for radiotherapy (RT) in mantle cell lymphoma (MCL) is limited as MCL often presents in advanced stages. A broader role may be rational given MCL’s propensity for profound but inconsistent radiosensitivity. Common molecular alterations in MCL impact prognosis, namely TP53 mutations (TP53mut). TP53mut can influence systemic therapy choices but its impact on radiosensitivity, or RT decision making is unclear. Better understanding could guide precision radiotherapy.</p><p><b>Methods:</b> We analyzed patients (pts) treated with RT for MCL from 2010 to 2024, focusing on a cohort with next generation sequencing (NGS) for somatic genetic alterations (<i>n</i> = 66). Age and stage at RT, treatment intent, relapsed status, site of RT, and prior systemic therapy were collected. Sites treated in pts with TP53mut versus without TP53mut (TP53wt) were compared. Lesion SUV and diameter, extranodal (EN) status of the treated site, blastoid histology, RT dose, and metabolic response at first assessment were compared. Additionally, sites receiving very low dose radiotherapy (VLDRT, 4 Gy) and sites of local failure (LF) were analyzed.</p><p><b>Results:</b> 66 patients were identified, treated to 97 sites. 84 sites (87%) were treated in the relapsed setting. 54 sites (56%) were localized relapsed or early-stage disease. By site, median follow up after RT was 1.5 years. 61 sites (64%) treated were EN. Median RT dose was 30 Gy (4–40 Gy), median lesion diameter was 3.5 cm (0.9–22 cm), and median SUV max was 7.5 (0–61.6). 80% (<i>n</i> = 77) of sites had available PET response assessment at a median of 1.7 months (0.1–7.1) post-RT. Overall response rate (ORR) was 98.7%, and complete response (CR) rate (CRR) was 81% (<i>n</i> = 62). 32% of pts (<i>n</i> = 21) treated to 33 sites (34%) harbored TP53mut. ORR and CRR were 100% and 83% in TP53wt and 96% and 80% in TP53mut. RT dose (<i>p</i> = 0.817) and CR% (<i>p</i> = 0.491) did not differ by TP53 status. When analyzed by site, TP53mut had significantly worse 1-year FFLP than TP53wt (100 % vs. 85%; <i>p</i> = 0.002). 6 sites overall (6.2%) had LF; of note, 4 of 6 sites received only 4 Gy. TP53mut status was associated with higher risk of LF (<i>p</i> = 0.024). Analysis of sites treated to 4 Gy (<i>n</i> = 14; 14.4%) revealed that TP53mut remained associated with increased risk of LF (<i>p</i> = 0.002). For sites receiving > 4 Gy (<i>n</i> = 83; Median dose 30 Gy, Range 10–40 Gy), presence of TP53mut (<i>n</i> = 30) suggested association with FFLP, though not signficant (<i>p</i> = 0.069). ORR and CRR was 100% and 82% for sites receiving > 4 gy and 89% and 79% for sites receiving VLDRT.</p><p><b>Conclusions:</b> In this cohort of MCL treated with RT, response was excellent, and LF was rare. Most sites of LF received VLDRT. TP53mut was significantly associated with higher risk of LF in sites treated with 4 Gy. Despite excellent responses to RT at higher, definitive doses, sites of pts wi
导言：放射治疗在套细胞淋巴瘤（MCL）中的作用有限，因为MCL通常出现在晚期。鉴于MCL具有深刻但不一致的放射敏感性，更广泛的作用可能是合理的。MCL中常见的影响预后的分子改变，即TP53突变（TP53mut）。TP53mut可以影响全身治疗的选择，但其对放射敏感性或放疗决策的影响尚不清楚。更好的理解可以指导精准放疗。方法：我们分析了2010年至2024年期间接受RT治疗的MCL患者（pts），重点分析了采用下一代测序（NGS）检测体细胞遗传改变的队列（n = 66）。收集年龄和放疗分期、治疗意图、复发状态、放疗部位和既往全身治疗。比较携带TP53mut和不携带TP53mut的患者的治疗部位（TP53wt）。比较病变的SUV和直径、治疗部位的结外（EN）状态、囊胚组织学、RT剂量和首次评估时的代谢反应。此外，还分析了极低剂量放疗（VLDRT, 4 Gy）和局部失败（LF）的部位。结果：确诊66例，治疗97个部位。84个部位（87%）接受了治疗。54个部位（56%）为局部复发或早期疾病。按部位划分，放疗后的中位随访时间为1.5年。61处（64%）为EN。中位放疗剂量为30 Gy (4 ~ 40 Gy)，中位病灶直径为3.5 cm (0.9 ~ 22 cm)，中位SUV max为7.5（0 ~ 61.6）。80% （n = 77）的地点在rt后中位时间为1.7个月（0.1-7.1个月）时进行了PET反应评估。总缓解率（ORR）为98.7%，完全缓解率（CRR）为81% （n = 62）。33个部位（34%）携带TP53mut的患者占32% （n = 21）。TP53wt的ORR和CRR分别为100%和83%，TP53mut的ORR和CRR分别为96%和80%。放疗剂量（p = 0.817）和CR% （p = 0.491）无TP53状态差异。通过位点分析，TP53mut的1年FFLP显著低于TP53wt (100% vs 85%；P = 0.002)。6个站点（6.2%）有LF；值得注意的是，6个地点中有4个只收到4戈瑞。TP53mut状态与LF的高风险相关（p = 0.024）。4 Gy处理部位分析(n = 14；14.4%)显示TP53mut仍与LF风险增加相关（p = 0.002）。对于接收>；4 Gy (n = 83；中位剂量30 Gy，范围10-40 Gy)， TP53mut的存在（n = 30）提示与FFLP相关，但不显著（p = 0.069）。接收>；接受VLDRT的部位分别为89%和79%。结论：在这组接受RT治疗的MCL患者中，疗效非常好，LF罕见。大部分LF部位接受VLDRT。在接受4gy治疗的部位，TP53mut与较高的LF风险显著相关。尽管在更高的确定剂量下对放射治疗有良好的反应，但TP53mut患者的部位对VLDRT的反应可能不太好，这表明相对放射耐药和需要考虑剂量增加或联合治疗策略。关键词：非霍奇金利益冲突潜在来源；顾问或顾问角色：Convergent R. N. R. LtdA。顾问或顾问角色：AstraZeneca， Genentech, Janssen Oncology， Kite pharmaceuticals股权：BridgeBio IncA。顾问或顾问角色：Abbvie， Arvinas Inc, Astrazeneca, BeiGene USA, bright Network LLC, Curio Science, Dava Oncology, Eli Lilly, Genentech, Kite pharmaceuticals。顾问或顾问角色：Abbvie, Aptitude Health, BeiGene USA Inc, Bristol-Myers Squibb, Celgene, Curio Science LLC, Debiopharm， Everest临床研究公司，Fondazione Ferrata Storti, GenMab, Incyte, Innate Pharma, Ipsen Pharma，杨森全球服务有限公司，杨森韩国有限公司，Kite制药，Medscape，默克，MJH生命科学，ModeX Therapeutics，诺华，Nurix, Orna, Practice Point Communications LLC, Research to Practice，罗氏，Scientific Education Support, Treeline biosciences。顾问或顾问角色：GT Medical Technologies Inc， Ono Pharma, Telix Pharmaceuticals Limited
{"title":"THE EFFECT OF TP53 MUTATIONS ON THE LOCAL RESPONSE OF MANTLE CELL LYMPHOMA TO RADIATION THERAPY","authors":"A. Deshane, J. Yahalom, N. A. Wijetunga, A. Kumar, B. Fregonese, A. Zelenetz, G. Salles, B. S. Imber","doi":"10.1002/hon.70094_268","DOIUrl":"https://doi.org/10.1002/hon.70094_268","url":null,"abstract":"<p><b>Introduction:</b> The role for radiotherapy (RT) in mantle cell lymphoma (MCL) is limited as MCL often presents in advanced stages. A broader role may be rational given MCL’s propensity for profound but inconsistent radiosensitivity. Common molecular alterations in MCL impact prognosis, namely TP53 mutations (TP53mut). TP53mut can influence systemic therapy choices but its impact on radiosensitivity, or RT decision making is unclear. Better understanding could guide precision radiotherapy.</p><p><b>Methods:</b> We analyzed patients (pts) treated with RT for MCL from 2010 to 2024, focusing on a cohort with next generation sequencing (NGS) for somatic genetic alterations (<i>n</i> = 66). Age and stage at RT, treatment intent, relapsed status, site of RT, and prior systemic therapy were collected. Sites treated in pts with TP53mut versus without TP53mut (TP53wt) were compared. Lesion SUV and diameter, extranodal (EN) status of the treated site, blastoid histology, RT dose, and metabolic response at first assessment were compared. Additionally, sites receiving very low dose radiotherapy (VLDRT, 4 Gy) and sites of local failure (LF) were analyzed.</p><p><b>Results:</b> 66 patients were identified, treated to 97 sites. 84 sites (87%) were treated in the relapsed setting. 54 sites (56%) were localized relapsed or early-stage disease. By site, median follow up after RT was 1.5 years. 61 sites (64%) treated were EN. Median RT dose was 30 Gy (4–40 Gy), median lesion diameter was 3.5 cm (0.9–22 cm), and median SUV max was 7.5 (0–61.6). 80% (<i>n</i> = 77) of sites had available PET response assessment at a median of 1.7 months (0.1–7.1) post-RT. Overall response rate (ORR) was 98.7%, and complete response (CR) rate (CRR) was 81% (<i>n</i> = 62). 32% of pts (<i>n</i> = 21) treated to 33 sites (34%) harbored TP53mut. ORR and CRR were 100% and 83% in TP53wt and 96% and 80% in TP53mut. RT dose (<i>p</i> = 0.817) and CR% (<i>p</i> = 0.491) did not differ by TP53 status. When analyzed by site, TP53mut had significantly worse 1-year FFLP than TP53wt (100 % vs. 85%; <i>p</i> = 0.002). 6 sites overall (6.2%) had LF; of note, 4 of 6 sites received only 4 Gy. TP53mut status was associated with higher risk of LF (<i>p</i> = 0.024). Analysis of sites treated to 4 Gy (<i>n</i> = 14; 14.4%) revealed that TP53mut remained associated with increased risk of LF (<i>p</i> = 0.002). For sites receiving > 4 Gy (<i>n</i> = 83; Median dose 30 Gy, Range 10–40 Gy), presence of TP53mut (<i>n</i> = 30) suggested association with FFLP, though not signficant (<i>p</i> = 0.069). ORR and CRR was 100% and 82% for sites receiving > 4 gy and 89% and 79% for sites receiving VLDRT.</p><p><b>Conclusions:</b> In this cohort of MCL treated with RT, response was excellent, and LF was rare. Most sites of LF received VLDRT. TP53mut was significantly associated with higher risk of LF in sites treated with 4 Gy. Despite excellent responses to RT at higher, definitive doses, sites of pts wi","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70094_268","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
P. Cramer, O. Al-Sawaf, E. Görgen, L. Mazot, S. Robrecht, M. Schüler-Aparicio, C. Paulitschek, A. Zey, A. Albrecht, J. Blau, L. Jung, S. Reidel, F. Bosch, C. da Cuna Bang, M. Doubek, E. Feyzi, A. Fink, P. Ghia, M. Gregor, R. Guieze, K. Jamroziak, A. Janssens, A. P. Kater, S. Kersting, P. Langerbeins, M. Levin, V. Lindström, M. Mattsson, C. Niemann, A. Quinquenel, M. Ritgen, L. Scarfò, P. Staber, S. Stilgenbauer, T. Tadmor, P. Thornton, E. Tausch, L. Ysebaert, K. Fischer, B. F. Eichhorst, M. Hallek
<p><b>Background:</b> The two major options for the first-line therapy of chronic lymphocytic leukemia (CLL) are a continuous BTK inhibitor treatment given as long as possible for disease control, or a venetoclax-based fixed-duration treatment, which usually leads to deep responses and a treatment-free interval of several years. There is an increased use of fixed-duration venetoclax-based regimens, such as venetoclax plus obinutuzumab (12 cycles) or venetoclax plus ibrutinib or acalabrutinib with/without obinutuzumab. While these combination therapies are more intense compared to monotherapies, the treatment-free interval carries advantages in terms of quality of life, safety and costs. The goal of this phase-III trial is to evaluate if a more individualized, but time-limited treatment duration is beneficial.</p><p><b>Methods:</b> Two treatment arms have a fixed-duration and one arm evaluates a treatment duration based on measurable residual disease (MRD):</p><p>— the standard arm A is the established combination of venetoclax and obinutuzumab (Ven-Obi, 12 cycles with a duration of 28 days, Obi only during cycles 1–6),</p><p>— arm B evaluates venetoclax plus pirtobrutinib (Ven-Pirto) for 15 cycles (3 cycles pirtobrutinib alone, then 12 cycles combined with venetoclax), and</p><p>— in arm C, Ven-Pirto will be administered for at least 15 and up to 36 cycles (as long as there is a deepening of response) until achievement of undetectable MRD (uMRD). To facilitate the transfer to clinical routine, MRD is measured in peripheral blood, by multi-colour flow cytometry and with a cut-off of 10<sup>−4</sup>. Two MRD assessments with an interval of 12 weeks both documenting uMRD are needed to allow for a treatment discontinuation and treatment will be continued for an additional 12 weeks after the second uMRD result as a consolidation.</p><p>813 patients with previously untreated CLL/SLL irrespective of age, comorbidities or CLL risk-factors will be recruited 1:1:1 to the three arms (271 each) with a stratification according to TP53 deletion and/or mutation, IGHV mutational status, disease type (CLL vs. SLL), and age. The primary endpoint is the investigator-assessed progression-free survival (PFS). The trial is designed to show both superiority of MRD-guided Ven-Pirto over Ven-Obi and over fixed duration Ven-Pirto. Secondary endpoints include iwCLL response, MRD, overall survival and safety parameters.</p><p><b>Results:</b> Recruitment is expected to start at the time of the ICML meeting. The estimated recruitment time of the 813 patients in approximately 160 sites in 16 countries is 20 months. Approximately 41 months after start of recruitment, a sufficient number of PFS events shall be reached for the primary endpoint analysis.</p><p><b>Summary/Conclusion:</b> The CLL18/MOIRAI trial will address the question whether an individualized, MRD-guided first-line treatment with pirtobrutinib and venetoclax improves the outcome of patients with CLL/SLL compared
{"title":"CLL18/MOIRAI TRIAL AIMING TO ESTABLISH MEASUREMENT OF INDIVIDUAL RESIDUAL DISEASE FOR ADJUSTMENT OF TREATMENT DURATION TO IMPROVE OUTCOMES IN TREATMENT-NAIVE CLL/SLL","authors":"P. Cramer, O. Al-Sawaf, E. Görgen, L. Mazot, S. Robrecht, M. Schüler-Aparicio, C. Paulitschek, A. Zey, A. Albrecht, J. Blau, L. Jung, S. Reidel, F. Bosch, C. da Cuna Bang, M. Doubek, E. Feyzi, A. Fink, P. Ghia, M. Gregor, R. Guieze, K. Jamroziak, A. Janssens, A. P. Kater, S. Kersting, P. Langerbeins, M. Levin, V. Lindström, M. Mattsson, C. Niemann, A. Quinquenel, M. Ritgen, L. Scarfò, P. Staber, S. Stilgenbauer, T. Tadmor, P. Thornton, E. Tausch, L. Ysebaert, K. Fischer, B. F. Eichhorst, M. Hallek","doi":"10.1002/hon.70093_OT02","DOIUrl":"https://doi.org/10.1002/hon.70093_OT02","url":null,"abstract":"<p><b>Background:</b> The two major options for the first-line therapy of chronic lymphocytic leukemia (CLL) are a continuous BTK inhibitor treatment given as long as possible for disease control, or a venetoclax-based fixed-duration treatment, which usually leads to deep responses and a treatment-free interval of several years. There is an increased use of fixed-duration venetoclax-based regimens, such as venetoclax plus obinutuzumab (12 cycles) or venetoclax plus ibrutinib or acalabrutinib with/without obinutuzumab. While these combination therapies are more intense compared to monotherapies, the treatment-free interval carries advantages in terms of quality of life, safety and costs. The goal of this phase-III trial is to evaluate if a more individualized, but time-limited treatment duration is beneficial.</p><p><b>Methods:</b> Two treatment arms have a fixed-duration and one arm evaluates a treatment duration based on measurable residual disease (MRD):</p><p>— the standard arm A is the established combination of venetoclax and obinutuzumab (Ven-Obi, 12 cycles with a duration of 28 days, Obi only during cycles 1–6),</p><p>— arm B evaluates venetoclax plus pirtobrutinib (Ven-Pirto) for 15 cycles (3 cycles pirtobrutinib alone, then 12 cycles combined with venetoclax), and</p><p>— in arm C, Ven-Pirto will be administered for at least 15 and up to 36 cycles (as long as there is a deepening of response) until achievement of undetectable MRD (uMRD). To facilitate the transfer to clinical routine, MRD is measured in peripheral blood, by multi-colour flow cytometry and with a cut-off of 10<sup>−4</sup>. Two MRD assessments with an interval of 12 weeks both documenting uMRD are needed to allow for a treatment discontinuation and treatment will be continued for an additional 12 weeks after the second uMRD result as a consolidation.</p><p>813 patients with previously untreated CLL/SLL irrespective of age, comorbidities or CLL risk-factors will be recruited 1:1:1 to the three arms (271 each) with a stratification according to TP53 deletion and/or mutation, IGHV mutational status, disease type (CLL vs. SLL), and age. The primary endpoint is the investigator-assessed progression-free survival (PFS). The trial is designed to show both superiority of MRD-guided Ven-Pirto over Ven-Obi and over fixed duration Ven-Pirto. Secondary endpoints include iwCLL response, MRD, overall survival and safety parameters.</p><p><b>Results:</b> Recruitment is expected to start at the time of the ICML meeting. The estimated recruitment time of the 813 patients in approximately 160 sites in 16 countries is 20 months. Approximately 41 months after start of recruitment, a sufficient number of PFS events shall be reached for the primary endpoint analysis.</p><p><b>Summary/Conclusion:</b> The CLL18/MOIRAI trial will address the question whether an individualized, MRD-guided first-line treatment with pirtobrutinib and venetoclax improves the outcome of patients with CLL/SLL compared ","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70093_OT02","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. Dedieu, H. Chanvrier, J. Carr-Klappert, A. Batista Mesquita Sauvage, S. Manciana, B. Van Meenen, M. Cote, T. Corbière, H. Auner, F. Solly, M. Eicher
<p>C. Dedieu, H. Chanvrier, and F. Solly equally contributing author.</p><p><b>Introduction:</b> Patients with hematological diseases, including blood cancers such as lymphoma or myeloma, often face significant difficulties in navigating health information about their illness due to the complexity of these conditions.</p><p>One of the self-reported educational needs of patients with hematological cancer is receiving clear and comprehensive information about laboratory results. Although these patients often undergo procedures such as venipuncture, knowledge gaps regarding laboratory results and biological concepts have been highlighted.</p><p>However, repeated procedures in combination with knowledge gaps and lack of information tailoring regarding laboratory results can decrease patient adherence and increase anxiety.</p><p>Our aim is to assess hematology patients’ knowledge of laboratory results and biological concepts, and their educational needs (format and frequency). We are also investigating patients’ interest in a novel biomedical consultation.</p><p><b>Methods:</b> This cross-sectional study is based on a digital self-reported questionnaire. Inpatients and outpatients over 18 years of age with a hematological disease and their caregivers are recruited at the Lausanne University Hospital by direct approach, flyers, patient associations or mail. The sample size of 103 was determined using Cochran’s formula, referencing a similar study. The questionnaire is divided into four sections consisting of (i) demographic information, (ii) general health literacy and disease awareness, (iii) preferences for educational interventions, and (iv) patient self-efficacy in managing laboratory results/biomedical information.</p><p><b>Results:</b> Preliminary results were obtained from 36 patients between November and December 2024. The largest group of participants were aged 60–75 years (42%), followed by those aged 75 years or older (25%). Patients with lymphoma and myeloma represented 5.6% and 22% of the participants respectively. Most participants (56%) rated their knowledge of biological concepts as average or poor. Only 19% of participants reported having a good understanding of blood counts. Understanding technical language and the meaning of laboratory results for their health was challenging according to 69%. Most participants (67%) expressed a desire to receive additional information regarding their laboratory results while 50% were interested in an individual educational biomedical consultation about laboratory analyses.</p><p><b>Conclusion:</b> These preliminary results provide valuable insights into patients' knowledge, unmet educational needs and preferences regarding educational formats. Recruitment is still ongoing, and we aim to present the final results at the conference. Our study will ultimately contribute to the development of an educational intervention to improve patients’ knowledge and self-management of laboratory results. Further st
C. Dedieu， H. Chanvrier和F. Solly都是贡献作者。导读：血液学疾病患者，包括血癌如淋巴瘤或骨髓瘤，由于这些疾病的复杂性，在浏览有关其疾病的健康信息时经常面临重大困难。血液病患者自我报告的教育需求之一是获得关于实验室结果的清晰和全面的信息。虽然这些患者经常接受诸如静脉穿刺之类的手术，但关于实验室结果和生物学概念的知识差距已经突出。然而，重复的程序加上知识差距和缺乏关于实验室结果的信息定制可能会降低患者的依从性并增加焦虑。我们的目的是评估血液病患者对实验室结果和生物学概念的知识，以及他们的教育需求（格式和频率）。我们也在调查患者对新型生物医学咨询的兴趣。方法：本横断面研究基于数字自我报告问卷。洛桑大学医院通过直接接触、传单、患者协会或邮件等方式招募18岁以上的血液病住院和门诊患者及其护理人员。103个样本的大小是根据科克伦公式确定的，参考了一个类似的研究。问卷分为四个部分，包括：(i)人口统计信息，（ii）一般卫生知识和疾病意识，（iii）对教育干预措施的偏好，以及（iv）患者在管理实验室结果/生物医学信息方面的自我效能。结果：2024年11 - 12月36例患者获得初步结果。最大的参与者群体是60-75岁（42%），其次是75岁及以上的人（25%）。淋巴瘤和骨髓瘤患者分别占参与者的5.6%和22%。大多数参与者（56%）认为他们对生物学概念的了解一般或较差。只有19%的参与者报告对血液计数有很好的了解。69%的人表示，理解技术语言和实验室结果对其健康的意义具有挑战性。大多数参与者（67%）表示希望获得有关其实验室结果的额外信息，而50%的人对有关实验室分析的个人教育生物医学咨询感兴趣。结论：这些初步结果为了解患者的知识、未满足的教育需求和对教育形式的偏好提供了有价值的见解。招聘仍在进行中，我们的目标是在会议上公布最终结果。我们的研究最终将有助于教育干预的发展，以提高患者对实验室结果的知识和自我管理。进一步的步骤将是使干预措施适应患者的特点，以提供个性化的、量身定制的教育支持。关键词：以病人和家庭为中心的护理潜在的利益冲突来源：M。顾问或顾问角色：ME所在机构因其在咨询委员会的活动而获得罗氏公司的报酬。其他报酬：ME所在机构因其在罗氏、BMS和Vifor的演讲和讲座而获得报酬
{"title":"EDUCATIONAL NEEDS OF SWISS PATIENTS WITH HEMATOLOGICAL DISEASES: FOCUS ON KNOWLEDGE REGARDING HEMATOLOGY LABORATORY RESULTS AND BIOMEDICAL CONCEPTS","authors":"C. Dedieu, H. Chanvrier, J. Carr-Klappert, A. Batista Mesquita Sauvage, S. Manciana, B. Van Meenen, M. Cote, T. Corbière, H. Auner, F. Solly, M. Eicher","doi":"10.1002/hon.70093_ON08","DOIUrl":"https://doi.org/10.1002/hon.70093_ON08","url":null,"abstract":"<p>C. Dedieu, H. Chanvrier, and F. Solly equally contributing author.</p><p><b>Introduction:</b> Patients with hematological diseases, including blood cancers such as lymphoma or myeloma, often face significant difficulties in navigating health information about their illness due to the complexity of these conditions.</p><p>One of the self-reported educational needs of patients with hematological cancer is receiving clear and comprehensive information about laboratory results. Although these patients often undergo procedures such as venipuncture, knowledge gaps regarding laboratory results and biological concepts have been highlighted.</p><p>However, repeated procedures in combination with knowledge gaps and lack of information tailoring regarding laboratory results can decrease patient adherence and increase anxiety.</p><p>Our aim is to assess hematology patients’ knowledge of laboratory results and biological concepts, and their educational needs (format and frequency). We are also investigating patients’ interest in a novel biomedical consultation.</p><p><b>Methods:</b> This cross-sectional study is based on a digital self-reported questionnaire. Inpatients and outpatients over 18 years of age with a hematological disease and their caregivers are recruited at the Lausanne University Hospital by direct approach, flyers, patient associations or mail. The sample size of 103 was determined using Cochran’s formula, referencing a similar study. The questionnaire is divided into four sections consisting of (i) demographic information, (ii) general health literacy and disease awareness, (iii) preferences for educational interventions, and (iv) patient self-efficacy in managing laboratory results/biomedical information.</p><p><b>Results:</b> Preliminary results were obtained from 36 patients between November and December 2024. The largest group of participants were aged 60–75 years (42%), followed by those aged 75 years or older (25%). Patients with lymphoma and myeloma represented 5.6% and 22% of the participants respectively. Most participants (56%) rated their knowledge of biological concepts as average or poor. Only 19% of participants reported having a good understanding of blood counts. Understanding technical language and the meaning of laboratory results for their health was challenging according to 69%. Most participants (67%) expressed a desire to receive additional information regarding their laboratory results while 50% were interested in an individual educational biomedical consultation about laboratory analyses.</p><p><b>Conclusion:</b> These preliminary results provide valuable insights into patients' knowledge, unmet educational needs and preferences regarding educational formats. Recruitment is still ongoing, and we aim to present the final results at the conference. Our study will ultimately contribute to the development of an educational intervention to improve patients’ knowledge and self-management of laboratory results. Further st","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70093_ON08","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
D. Piffaretti, I. Romano, J. Marquez de Almeida, M. Salehi, H. Javanmard Khameneh, R. Moia, A. Bruscaggin, F. Jauk, S. Bocchetta, A. Condoluci, G. Forestieri, M. C. Pirosa, L. Terzi di Bergamo, S. Schär, A. Zenobi, A. Stathis, S. Monticelli, G. Gaidano, G. Guarda, D. Rossi
<p>D. Piffaretti and I. Romano equally contributing authors.</p><p><b>Introduction:</b> Clonal Hematopoiesis (CH) may promote diffuse large B-cell lymphoma (DLBCL) in two ways: by seeding mutations in the B-cells progenitors, potentially contributing to malignant transformation. Alternatively, lymphoma may be promoted by the clonal and pro-inflammatory tumor microenvironment derived from CH. In this study we aimed to determine: (i) CH prevalence in newly diagnosed DLBCL; (ii) clinical impact of CH; (iii) correlation between CH and DLBCL genetic lesions; (iv) co-occurrence frequency of DLBCL driver and CH mutations at the single cell level; (v) enrichment of CH in cells of the lymphoma microenvironment compared to blood.</p><p><b>Methods:</b> Patients (<i>n</i> = 387) from the IOSI-EMA003 and SAKK38/19 trials were analyzed. CH mutations were identified in genomic DNA using a myeloid panel, while a lymphoid panel detected DLBCL mutations, somatic copy number abnormalities, and <i>BCL6</i> fusions in plasma cfDNA. Multiomic scDNA-seq and immunophenotyping of paired peripheral blood (PB) or bone marrow (BM) and disaggregated lymph nodes of 6 patients were performed. A custom Tapestri (MissionBio) panel targeted CH mutations and barcoded the dominant DLBCL clone by covering trunk oncogene mutations, enabling simultaneous genotyping and phenotyping of B cells, T cell subtypes, and myeloid cells. To assess whether CH-bearing myeloid cells support DLBCL in vitro: (i) BM cells from <i>Tet2</i> knockout (KO) and control mice were differentiated into macrophages and co-cultured with a <i>Tp53</i> KO murine B-cell lymphoma line; (ii) biallelic <i>TET2-</i>KO human THP1 monocytic cells, were differentiated into macrophages and co-cultured with DLBCL cell lines. Additionally, lymphoma-prone <i>Klf2</i><sup><i>fl/fl</i></sup><i>/Notch2IC</i><sup><i>fl/+</i></sup><i>/Cd19Cre</i><sup><i>+/</i>−</sup>/<i>Cd</i>45<i>.2</i><sup>+/+</sup> oncogenic and <i>Cd19Cre</i><sup><i>+/</i>−</sup>/<i>Cd45.2</i><sup>+/−</sup> control mice were adoptively transplanted with BM cells from <i>Tet</i>2<sup>+/+</sup>, <i>Tet</i>2<sup>+/−</sup>, and <i>Tet2</i><sup>−/−</sup> C57BL/6 <i>Cd45.1</i><sup>+/−</sup> mice without conditioning.</p><p><b>Results:</b> The analysis was done including patients per the CONSORT diagram (Figure 1A). CH mutations (VAF > 1%) were found in 38% of patients, primarily in <i>DNMT3A</i> and <i>TET2</i>, and correlated with age (Figure 1B). However, CH showed no association with features of lymphoma aggressiveness (clinical stage, B-symptoms, IPI) or DLBCL subtypes (cell of origin, C1-C5). Cox analyses (univariate/multivariate, adjusted for IPI), revealed no impact of CH on progression-free survival or lymphoma-specific survival. In vitro, lymphoma cell survival was limitedly affected by <i>TET2</i> status in macrophages. Engraftment in control mice mirrored the typical load of CH in humans (∼1% PB leukocytes at 3 months), whereas <i>Tet</i>2<sup>+/−</su
{"title":"CLONAL HEMATOPOIESIS IN DIFFUSE LARGE B-CELL LYMPHOMA","authors":"D. Piffaretti, I. Romano, J. Marquez de Almeida, M. Salehi, H. Javanmard Khameneh, R. Moia, A. Bruscaggin, F. Jauk, S. Bocchetta, A. Condoluci, G. Forestieri, M. C. Pirosa, L. Terzi di Bergamo, S. Schär, A. Zenobi, A. Stathis, S. Monticelli, G. Gaidano, G. Guarda, D. Rossi","doi":"10.1002/hon.70093_60","DOIUrl":"https://doi.org/10.1002/hon.70093_60","url":null,"abstract":"<p>D. Piffaretti and I. Romano equally contributing authors.</p><p><b>Introduction:</b> Clonal Hematopoiesis (CH) may promote diffuse large B-cell lymphoma (DLBCL) in two ways: by seeding mutations in the B-cells progenitors, potentially contributing to malignant transformation. Alternatively, lymphoma may be promoted by the clonal and pro-inflammatory tumor microenvironment derived from CH. In this study we aimed to determine: (i) CH prevalence in newly diagnosed DLBCL; (ii) clinical impact of CH; (iii) correlation between CH and DLBCL genetic lesions; (iv) co-occurrence frequency of DLBCL driver and CH mutations at the single cell level; (v) enrichment of CH in cells of the lymphoma microenvironment compared to blood.</p><p><b>Methods:</b> Patients (<i>n</i> = 387) from the IOSI-EMA003 and SAKK38/19 trials were analyzed. CH mutations were identified in genomic DNA using a myeloid panel, while a lymphoid panel detected DLBCL mutations, somatic copy number abnormalities, and <i>BCL6</i> fusions in plasma cfDNA. Multiomic scDNA-seq and immunophenotyping of paired peripheral blood (PB) or bone marrow (BM) and disaggregated lymph nodes of 6 patients were performed. A custom Tapestri (MissionBio) panel targeted CH mutations and barcoded the dominant DLBCL clone by covering trunk oncogene mutations, enabling simultaneous genotyping and phenotyping of B cells, T cell subtypes, and myeloid cells. To assess whether CH-bearing myeloid cells support DLBCL in vitro: (i) BM cells from <i>Tet2</i> knockout (KO) and control mice were differentiated into macrophages and co-cultured with a <i>Tp53</i> KO murine B-cell lymphoma line; (ii) biallelic <i>TET2-</i>KO human THP1 monocytic cells, were differentiated into macrophages and co-cultured with DLBCL cell lines. Additionally, lymphoma-prone <i>Klf2</i><sup><i>fl/fl</i></sup><i>/Notch2IC</i><sup><i>fl/+</i></sup><i>/Cd19Cre</i><sup><i>+/</i>−</sup>/<i>Cd</i>45<i>.2</i><sup>+/+</sup> oncogenic and <i>Cd19Cre</i><sup><i>+/</i>−</sup>/<i>Cd45.2</i><sup>+/−</sup> control mice were adoptively transplanted with BM cells from <i>Tet</i>2<sup>+/+</sup>, <i>Tet</i>2<sup>+/−</sup>, and <i>Tet2</i><sup>−/−</sup> C57BL/6 <i>Cd45.1</i><sup>+/−</sup> mice without conditioning.</p><p><b>Results:</b> The analysis was done including patients per the CONSORT diagram (Figure 1A). CH mutations (VAF > 1%) were found in 38% of patients, primarily in <i>DNMT3A</i> and <i>TET2</i>, and correlated with age (Figure 1B). However, CH showed no association with features of lymphoma aggressiveness (clinical stage, B-symptoms, IPI) or DLBCL subtypes (cell of origin, C1-C5). Cox analyses (univariate/multivariate, adjusted for IPI), revealed no impact of CH on progression-free survival or lymphoma-specific survival. In vitro, lymphoma cell survival was limitedly affected by <i>TET2</i> status in macrophages. Engraftment in control mice mirrored the typical load of CH in humans (∼1% PB leukocytes at 3 months), whereas <i>Tet</i>2<sup>+/−</su","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70093_60","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
H. Zhong, C. Chen, S. Cheng, G. Cai, P. Sun, P. Liu, P. Xu, M. Cai, H. Yang, J. Xiong, Y. Wang, Y. Huang, J. Zhao, H. Yang, J. Chen, L. Wang, S. Luminari, E. Zucca, F. Cavalli, Z. Li, W. Zhao
<p>H. Zhong, C. Chen, S. Cheng, G. Cai, P. Sun, P. Liu Z. Li, and W. Zhao equally contributing authors.</p><p><b>Introduction:</b> Natural killer/T-cell lymphoma (NKTCL) is highly aggressive and characterized by Epstein-Barr virus (EBV) infection and overexpression of immune checkpoints. The therapeutic options were limited for patients unsuitable for chemotherapy. Immune checkpoint inhibitors have been shown effective in refractory and relapsed NKTCL. This study aims to investigate the efficacy and safety of programmed death 1 (PD-1) antibody pembrolizumab concurrent with radiotherapy as a first-line treatment in newly diagnosed early-stage frail NKTCL patients.</p><p><b>Methods:</b> This is a multicenter phase II study. Eligible patients met the following criteria: (1) age ≥ 18 years; (2) newly diagnosed NKTCL with Ann Arbor stage I-II disease; (3) presence of at least one risk factor (age > 60 years, elevated serum lactate dehydrogenase, Ann Arbor stage II or primary tumor invasion); (4) unsuitable for systemic chemotherapy. All patients received induction treatment with pembrolizumab (200 mg intravenously on day 1 in each 21-day cycle for 6 cycles) concurrently with radiotherapy (a total dose of 50–54 Gy). The patients achieved complete remission (CR), partial remission (PR), or stable disease (SD) have been given pembrolizumab 200 mg every 21 days as a maintenance up to 2 years. The primary endpoint was 2-year progression-free survival (PFS) rate. The main secondary endpoints included CR rate (CRR), overall response rate (ORR), adverse events and plasma EBV DNA change.</p><p><b>Results:</b> From August 2020 to January 2025, a total of 30 patients with median age of 62 (20–74) years were enrolled in Shanghai Ruijin Hospital and Guangzhou Sun Yat Sen University Cancer Center. All patients were intermediate (60%, <i>n</i> = 18) and high (40%, <i>n</i> = 12) risk according to nomogram-revised risk index. Until February 2025, 62.5% CRR (95% CI: 40.6%–81.2%) and 91.7% ORR (95% CI: 73.0%–99.0%) have been achieved in twenty-four evaluable patients after induction treatment. With median follow-up time of 10.2 months (not yet mature for the analysis of the primary endpoint), the best CRR and ORR were 83.3% (95% CI: 62.6%–95.3%) and 91.7% (95% CI: 73.0%%–99.0%), respectively (Figure). The responses improved with the increase of cycles. The most common adverse events were lymphocytopenia, leukopenia, oral mucositis, radiodermatitis and dry mouth. Grade 3/4 adverse events were low, including lymphocytopenia (16.6%) and oral mucositis (13.3%). The treatment was well-tolerated. Among patients who were EBV DNA positive before treatment, 70% achieved EBV DNA negativity following induction therapy.</p><p><b>Conclusion:</b> Pembrolizumab concurrent with radiotherapy was effective and safe in newly diagnosed early-stage frail NKTCL patients, even in those with intermediate or high risk. Immune checkpoint inhibitors could be applied as first-line alternative
{"title":"A PHASE II TRIAL OF PEMBROLIZUMAB CONCURRENT WITH RADIOTHERAPY FOR FRAIL PATIENTS WITH NEWLY DIAGNOSED EARLY-STAGE NATURAL KILLER/T-CELL LYMPHOMA (IELSG50)","authors":"H. Zhong, C. Chen, S. Cheng, G. Cai, P. Sun, P. Liu, P. Xu, M. Cai, H. Yang, J. Xiong, Y. Wang, Y. Huang, J. Zhao, H. Yang, J. Chen, L. Wang, S. Luminari, E. Zucca, F. Cavalli, Z. Li, W. Zhao","doi":"10.1002/hon.70093_62","DOIUrl":"https://doi.org/10.1002/hon.70093_62","url":null,"abstract":"<p>H. Zhong, C. Chen, S. Cheng, G. Cai, P. Sun, P. Liu Z. Li, and W. Zhao equally contributing authors.</p><p><b>Introduction:</b> Natural killer/T-cell lymphoma (NKTCL) is highly aggressive and characterized by Epstein-Barr virus (EBV) infection and overexpression of immune checkpoints. The therapeutic options were limited for patients unsuitable for chemotherapy. Immune checkpoint inhibitors have been shown effective in refractory and relapsed NKTCL. This study aims to investigate the efficacy and safety of programmed death 1 (PD-1) antibody pembrolizumab concurrent with radiotherapy as a first-line treatment in newly diagnosed early-stage frail NKTCL patients.</p><p><b>Methods:</b> This is a multicenter phase II study. Eligible patients met the following criteria: (1) age ≥ 18 years; (2) newly diagnosed NKTCL with Ann Arbor stage I-II disease; (3) presence of at least one risk factor (age > 60 years, elevated serum lactate dehydrogenase, Ann Arbor stage II or primary tumor invasion); (4) unsuitable for systemic chemotherapy. All patients received induction treatment with pembrolizumab (200 mg intravenously on day 1 in each 21-day cycle for 6 cycles) concurrently with radiotherapy (a total dose of 50–54 Gy). The patients achieved complete remission (CR), partial remission (PR), or stable disease (SD) have been given pembrolizumab 200 mg every 21 days as a maintenance up to 2 years. The primary endpoint was 2-year progression-free survival (PFS) rate. The main secondary endpoints included CR rate (CRR), overall response rate (ORR), adverse events and plasma EBV DNA change.</p><p><b>Results:</b> From August 2020 to January 2025, a total of 30 patients with median age of 62 (20–74) years were enrolled in Shanghai Ruijin Hospital and Guangzhou Sun Yat Sen University Cancer Center. All patients were intermediate (60%, <i>n</i> = 18) and high (40%, <i>n</i> = 12) risk according to nomogram-revised risk index. Until February 2025, 62.5% CRR (95% CI: 40.6%–81.2%) and 91.7% ORR (95% CI: 73.0%–99.0%) have been achieved in twenty-four evaluable patients after induction treatment. With median follow-up time of 10.2 months (not yet mature for the analysis of the primary endpoint), the best CRR and ORR were 83.3% (95% CI: 62.6%–95.3%) and 91.7% (95% CI: 73.0%%–99.0%), respectively (Figure). The responses improved with the increase of cycles. The most common adverse events were lymphocytopenia, leukopenia, oral mucositis, radiodermatitis and dry mouth. Grade 3/4 adverse events were low, including lymphocytopenia (16.6%) and oral mucositis (13.3%). The treatment was well-tolerated. Among patients who were EBV DNA positive before treatment, 70% achieved EBV DNA negativity following induction therapy.</p><p><b>Conclusion:</b> Pembrolizumab concurrent with radiotherapy was effective and safe in newly diagnosed early-stage frail NKTCL patients, even in those with intermediate or high risk. Immune checkpoint inhibitors could be applied as first-line alternative ","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70093_62","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Y. Li, L. Jin, Y. Duan, W. Liu, J. Zhou, F. Li, X. Yang, Y. Jia, K. Yang, Y. Liu, Y. Dai, L. Yang, A. Liu, P. Wu, R. Liu, L. Jiang, X. Yuan, J. Jiang, S. Zhuang, J. Wang, Z. Xu, H. Gao, Q. Zheng, Y. Zhang
<p>Y. Li, L. Jin, Q. Zheng, and Y. Zhang equally contributing authors.</p><p><b>Introduction:</b> T-cell lymphoblastic lymphoma (T-LBL) is a highly aggressive malignancy with a high incidence among children and adolescents. Despite its prevalence, research on fusion genes in T-LBL, particularly their distribution and prognostic implications, remains limited. This study aimed to elucidate the frequency of fusion genes in Chinese pediatric T-LBL patients and explore their potential impact on prognosis, thereby providing new insights for clinical management.</p><p><b>Methods:</b> We collected data from 552 pediatric T-LBL patients (aged ≤ 16 years) treated at multiple centers of the China Network of Childhood Lymphoma (CNCL), with fusion gene testing results available for 180 patients. Sequencing-based methods were used to detect fusion genes, and statistical analysis was performed to investigate their associations with patient clinical outcomes.</p><p><b>Results:</b> Among the 180 patients analyzed, 105 (58.3%) were found to harbor fusion genes, with a total of 40 distinct fusion genes identified. The higher percentage of fusion genes were <i>SIL</i>::<i>TAL1</i> (<i>n</i> = 40, 22.2%), <i>MLL</i> fusions (<i>n</i> = 20, 11.1%), <i>TCR</i> partner-related fusions (<i>n</i> = 11, 6.1%), <i>ABL1</i> fusions (<i>n</i> = 9, 5%), <i>NOTCH1</i> fusions (<i>n</i> = 7, 3.9%), and <i>SET</i>::<i>CAN</i> (<i>n</i> = 7, 3.9%) (Figure 1a). These findings highlight the genetic heterogeneity of T-LBL in pediatric patients.</p><p>Prognostic analysis revealed that patients with <i>NOTCH1</i> fusions had significantly poorer event-free survival (EFS) and overall survival (OS) compared to those without <i>NOTCH1</i> fusions (EFS, <i>p</i> < 0.0001; OS, <i>p</i> = 0.00013, Figure 1b,c). The identified <i>NOTCH1</i> fusion types included <i>IKZF2</i>::<i>NOTCH1</i> (<i>n</i> = 4, 57%), <i>MIR142</i>::<i>NOTCH1</i> (<i>n</i> = 2, 29%) and <i>IKZF1</i>::<i>NOTCH1</i> (<i>n</i> = 1, 14%), all of which are associated with poor outcomes. We further analyzed the relationship between <i>NOTCH1</i> mutations and <i>NOTCH1</i> fusions, and there was no obvious evidence of co-occurrence or mutual exclusivity between these genetic events. Notably, although <i>NOTCH1</i> mutations are generally associated with favorable outcomes in pediatric T-LBL patients, the cooccurrence of <i>NOTCH1</i> fusions appeared to diminish this benefit, showing a trend toward poorer prognosis (<i>p</i> = 0.056). These findings indicate that <i>NOTCH1</i> fusions may serve as potential biomarkers for adverse prognosis in pediatric patients with T-LBL. Additionally, <i>SIL::TAL1</i> and <i>MLL</i> fusions were observed but showed no prognostic significance in this cohort, warranting further study in larger cohorts.</p><p><b>Conclusion:</b> Our study provides the comprehensive overview of fusion gene distribution in Chinese pediatric T-LBL patients and highlights the significant prognostic impact of
{"title":"FREQUENCY OF FUSION GENES AND THEIR CLINICAL IMPACTS IN CHINESE PEDIATRIC PATIENTS WITH T-CELL LYMPHOBLASTIC LYMPHOMA","authors":"Y. Li, L. Jin, Y. Duan, W. Liu, J. Zhou, F. Li, X. Yang, Y. Jia, K. Yang, Y. Liu, Y. Dai, L. Yang, A. Liu, P. Wu, R. Liu, L. Jiang, X. Yuan, J. Jiang, S. Zhuang, J. Wang, Z. Xu, H. Gao, Q. Zheng, Y. Zhang","doi":"10.1002/hon.70093_36","DOIUrl":"https://doi.org/10.1002/hon.70093_36","url":null,"abstract":"<p>Y. Li, L. Jin, Q. Zheng, and Y. Zhang equally contributing authors.</p><p><b>Introduction:</b> T-cell lymphoblastic lymphoma (T-LBL) is a highly aggressive malignancy with a high incidence among children and adolescents. Despite its prevalence, research on fusion genes in T-LBL, particularly their distribution and prognostic implications, remains limited. This study aimed to elucidate the frequency of fusion genes in Chinese pediatric T-LBL patients and explore their potential impact on prognosis, thereby providing new insights for clinical management.</p><p><b>Methods:</b> We collected data from 552 pediatric T-LBL patients (aged ≤ 16 years) treated at multiple centers of the China Network of Childhood Lymphoma (CNCL), with fusion gene testing results available for 180 patients. Sequencing-based methods were used to detect fusion genes, and statistical analysis was performed to investigate their associations with patient clinical outcomes.</p><p><b>Results:</b> Among the 180 patients analyzed, 105 (58.3%) were found to harbor fusion genes, with a total of 40 distinct fusion genes identified. The higher percentage of fusion genes were <i>SIL</i>::<i>TAL1</i> (<i>n</i> = 40, 22.2%), <i>MLL</i> fusions (<i>n</i> = 20, 11.1%), <i>TCR</i> partner-related fusions (<i>n</i> = 11, 6.1%), <i>ABL1</i> fusions (<i>n</i> = 9, 5%), <i>NOTCH1</i> fusions (<i>n</i> = 7, 3.9%), and <i>SET</i>::<i>CAN</i> (<i>n</i> = 7, 3.9%) (Figure 1a). These findings highlight the genetic heterogeneity of T-LBL in pediatric patients.</p><p>Prognostic analysis revealed that patients with <i>NOTCH1</i> fusions had significantly poorer event-free survival (EFS) and overall survival (OS) compared to those without <i>NOTCH1</i> fusions (EFS, <i>p</i> < 0.0001; OS, <i>p</i> = 0.00013, Figure 1b,c). The identified <i>NOTCH1</i> fusion types included <i>IKZF2</i>::<i>NOTCH1</i> (<i>n</i> = 4, 57%), <i>MIR142</i>::<i>NOTCH1</i> (<i>n</i> = 2, 29%) and <i>IKZF1</i>::<i>NOTCH1</i> (<i>n</i> = 1, 14%), all of which are associated with poor outcomes. We further analyzed the relationship between <i>NOTCH1</i> mutations and <i>NOTCH1</i> fusions, and there was no obvious evidence of co-occurrence or mutual exclusivity between these genetic events. Notably, although <i>NOTCH1</i> mutations are generally associated with favorable outcomes in pediatric T-LBL patients, the cooccurrence of <i>NOTCH1</i> fusions appeared to diminish this benefit, showing a trend toward poorer prognosis (<i>p</i> = 0.056). These findings indicate that <i>NOTCH1</i> fusions may serve as potential biomarkers for adverse prognosis in pediatric patients with T-LBL. Additionally, <i>SIL::TAL1</i> and <i>MLL</i> fusions were observed but showed no prognostic significance in this cohort, warranting further study in larger cohorts.</p><p><b>Conclusion:</b> Our study provides the comprehensive overview of fusion gene distribution in Chinese pediatric T-LBL patients and highlights the significant prognostic impact of ","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70093_36","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. S. Tam, P. Ghia, M. Shadman, T. Munir, S. S. Opat, P. A. Walker, M. Lasica, I. W. Flinn, T. Tian, S. Agresti, J. Hirata, J. R. Brown
<p><b>Introduction:</b> Zanubrutinib is a next-generation Bruton tyrosine kinase inhibitor that is approved for five indications, including CLL/SLL. Initial results from the SEQUOIA study (NCT03336333), at a median follow-up of 26.2 months, demonstrated superior progression-free survival (PFS) by independent review with zanubrutinib versus bendamustine + rituximab (arms A and B) in patients with treatment-naive CLL/SLL without del(17p) as well as high overall response rate (ORR) and PFS benefit in patients with del(17p) (arm C). Additionally, the 5-year follow-up in arm A demonstrated durable PFS benefit, with estimated 54- and 60-month PFS rates of 80% and 76%, respectively. Here we report updated results in SEQUOIA arm C, in patients with del(17p), after approximately 5 years of follow-up (data cutoff: Apr 30, 2024).</p><p><b>Methods:</b> Arm C is a nonrandomized cohort of SEQUOIA patients with del(17p) that received zanubrutinib monotherapy. Investigator-assessed PFS, overall survival (OS), ORR, and safety/tolerability were evaluated. Adverse events (AEs) were recorded until disease progression or start of next-line therapy.</p><p><b>Results:</b> Between Feb 2018 and Mar 2019, 111 treatment-naive patients with del(17p) were enrolled to receive zanubrutinib. The median age was 71 years (range, 42–87 years), 79 (71%) were male, 67 (60%) were IGHV unmutated, and 47 (42%) had both del(17p) and <i>TP53</i> mutation. At a median follow-up of 65.8 months (range, 5–75 months), median PFS was not reached. The estimated 60-month PFS rate was 72.2% (62.4%–79.8%) (Figure), or 73.0% (63.3%–80.6%) when adjusted for COVID-19. Median OS was also not reached. The estimated 60-month OS rate was 85.1% (76.9%–90.6%), or 87.0% (79.0%–92.1%) when adjusted for COVID-19. The ORR was 97.3%, and the complete response/complete response with incomplete hematologic recovery rate was 18.2%. Zanubrutinib treatment was ongoing in 62.2% of patients. The most common causes for treatment discontinuation were AEs and progressive disease (in 17.1% and 15.3%, respectively). Key AEs of interest (AEI) included any-grade infection (82%), bleeding (60%), neutropenia (19%), hypertension (18%), anemia (9%), thrombocytopenia (8%), and atrial fibrillation/flutter (7%). Grade ≥ 3 AEI included infection (33%), neutropenia (16%), hypertension (8%), bleeding (6%), atrial fibrillation/flutter (5%), and thrombocytopenia (2%).</p><p><b>Conclusions:</b> With this 5-year follow-up in SEQUOIA, the efficacy of zanubrutinib in treatment-naive higher-risk patients with del(17p) was maintained, and patients continue to demonstrate PFS benefits consistent with the randomized cohort of patients without del(17p) (arm A). Additionally, with longer-term follow-up, no new safety signals were identified. This update, in the largest cohort of uniformly treated patients with del(17p), suggests that zanubrutinib remains a valuable frontline treatment option for patients with or without del(17p) CLL/SLL.</p><p><b
{"title":"SEQUOIA 5-YEAR FOLLOW-UP IN ARM C: FRONTLINE ZANUBRUTINIB IN PATIENTS WITH DEL(17P) AND TREATMENT-NAIVE CHRONIC LYMPHOCYTIC LEUKEMIA/SMALL LYMPHOCYTIC LYMPHOMA (CLL/SLL)","authors":"C. S. Tam, P. Ghia, M. Shadman, T. Munir, S. S. Opat, P. A. Walker, M. Lasica, I. W. Flinn, T. Tian, S. Agresti, J. Hirata, J. R. Brown","doi":"10.1002/hon.70093_72","DOIUrl":"https://doi.org/10.1002/hon.70093_72","url":null,"abstract":"<p><b>Introduction:</b> Zanubrutinib is a next-generation Bruton tyrosine kinase inhibitor that is approved for five indications, including CLL/SLL. Initial results from the SEQUOIA study (NCT03336333), at a median follow-up of 26.2 months, demonstrated superior progression-free survival (PFS) by independent review with zanubrutinib versus bendamustine + rituximab (arms A and B) in patients with treatment-naive CLL/SLL without del(17p) as well as high overall response rate (ORR) and PFS benefit in patients with del(17p) (arm C). Additionally, the 5-year follow-up in arm A demonstrated durable PFS benefit, with estimated 54- and 60-month PFS rates of 80% and 76%, respectively. Here we report updated results in SEQUOIA arm C, in patients with del(17p), after approximately 5 years of follow-up (data cutoff: Apr 30, 2024).</p><p><b>Methods:</b> Arm C is a nonrandomized cohort of SEQUOIA patients with del(17p) that received zanubrutinib monotherapy. Investigator-assessed PFS, overall survival (OS), ORR, and safety/tolerability were evaluated. Adverse events (AEs) were recorded until disease progression or start of next-line therapy.</p><p><b>Results:</b> Between Feb 2018 and Mar 2019, 111 treatment-naive patients with del(17p) were enrolled to receive zanubrutinib. The median age was 71 years (range, 42–87 years), 79 (71%) were male, 67 (60%) were IGHV unmutated, and 47 (42%) had both del(17p) and <i>TP53</i> mutation. At a median follow-up of 65.8 months (range, 5–75 months), median PFS was not reached. The estimated 60-month PFS rate was 72.2% (62.4%–79.8%) (Figure), or 73.0% (63.3%–80.6%) when adjusted for COVID-19. Median OS was also not reached. The estimated 60-month OS rate was 85.1% (76.9%–90.6%), or 87.0% (79.0%–92.1%) when adjusted for COVID-19. The ORR was 97.3%, and the complete response/complete response with incomplete hematologic recovery rate was 18.2%. Zanubrutinib treatment was ongoing in 62.2% of patients. The most common causes for treatment discontinuation were AEs and progressive disease (in 17.1% and 15.3%, respectively). Key AEs of interest (AEI) included any-grade infection (82%), bleeding (60%), neutropenia (19%), hypertension (18%), anemia (9%), thrombocytopenia (8%), and atrial fibrillation/flutter (7%). Grade ≥ 3 AEI included infection (33%), neutropenia (16%), hypertension (8%), bleeding (6%), atrial fibrillation/flutter (5%), and thrombocytopenia (2%).</p><p><b>Conclusions:</b> With this 5-year follow-up in SEQUOIA, the efficacy of zanubrutinib in treatment-naive higher-risk patients with del(17p) was maintained, and patients continue to demonstrate PFS benefits consistent with the randomized cohort of patients without del(17p) (arm A). Additionally, with longer-term follow-up, no new safety signals were identified. This update, in the largest cohort of uniformly treated patients with del(17p), suggests that zanubrutinib remains a valuable frontline treatment option for patients with or without del(17p) CLL/SLL.</p><p><b","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70093_72","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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