T. Vassilakopoulos, Z. Mellios, G. Papageorgiou, A. Piperidou, E. Verigou, C. Chatzidimitriou, C. Kalpadakis, E. Katodritou, H. Giatra, V. Xanthopoulos, G. Gainaru, E. Vrakidou, T. Leonidopoulou, M. Kotsopoulou, M. Palassopoulou, S. Karakatsanis, M. Tsirogianni, E. Hatzimichael, E. Terpos, P. Zikos, C. Poziopoulos, E. Vervessou, M. Arapaki, A. Kopsaftopoulou, A. Liaskas, P. Katsaouni, J. Assimakopoulos, G. Kourti, D. Koutsiafes, M. Siakantaris, G. Karianakis, A. Symeonidis, D. Grentzelias, V. Pappa, P. Tsirigotis, E. Papadaki, E. Plata, M. Bakiri, G. Pangalis, M. Angelopoulou, M. Bouzani
<p><b>Background:</b> Further to the impressive phase 2 NCI results, retrospective comparisons have shown a modest, non-significant benefit in disease control and a reduced need for consolidative radiotherapy (RT) with R-da-EPOCH versus R-CHOP in PMLBCL. However, the numbers of patients were small-to-moderate (<< 100) and the choice of treatment was at the discretion of the treating physician, inevitably introducing systematic bias.</p><p><b>Aims:</b> To evaluate the efficacy of R-da-EPOCH versus R-CHOP with an -as much as possible- unbiased selection of control group patients</p><p><b>Methods:</b> R-da-EPOCH was adopted in all consecutive patients with PMLBCL ≤ 65 years (<i>n</i> = 156) in 18 participating Centers, which were providing R-CHOP as standard of care until that time. The control group of R-CHOP-treated patients was devised from the same Centers’ database, selecting in chronological order (most recent first) an equal number of consecutive patients to those treated with R-da-EPOCH at the same Center, if possible, thus minimizing selection bias. Due to lack of some appropriate controls in a few Centers (< 20 R-CHOP-treated patients less), they were substituted by consecutive patients treated in few of the other centers, which had comparable potential (large or small, public or private centers). R-CHOP-14 was given in 22/156 patients of the control group (14%).</p><p><b>Results:</b> The groups of R-da-EPOCH (<i>n</i> = 156) and R-CHOP-treated patients (<i>n</i> = 156) were absolutely comparable in terms of patients’ characteristics except for more frequent multiple extranodal involvement in R-CHOP (8.4% vs. 16.0%, <i>p</i> = 0.042). The 5-year freedom from progression (FFP), event-free survival (EFS) and overall survival (OS) rates for R-da-EPOCH versus R-CHOP were 87.5% versus 75.5% (<i>p</i> = 0.011), 84.4% versus 75.5% (<i>p</i> = 0.052 counting 4 t-AML cases after R-da-EPOCH as events) and 94.1% versus 86.9% (<i>p</i> = 0.039). Among patients potentially eligible for RT (no progressive disease), RT was administered to 10% versus 70% after R-da-EPOCH or R-CHOP. In multivariate analysis, after adjustment for age, gender, multiple extranodal sites and recently published prognostic models (extranodal and LDH > 2x or bulk) the difference between R-da-EPOCH and R-CHOP remained significant regarding FFP, OS and EFS, when the extranodal-LDH model was assessed, but only for FFP when the extranodal-bulk model was taken into account (0.10 < <i>p</i> < 0.20 for EFS and OS). Only 77 (58%) of 133 patients with currently available data had absolute adherence to R-da-EPOCH protocol, reflecting the real-life situation. These patients had a 5-year FFP of 90.9% and 85.1% (<i>p</i> = 0.30).</p><p><b>Conclusion:</b> Our non-randomized, comparative study is by far the largest one comparing R-da-EPOCH versus R-CHOP and carried the least possible systematic error in the retrospective setting. R-da-EPOCH minimized the need of RT and demonst
{"title":"RITUXIMAB-DOSE-ADJUSTED EPOCH VERSUS RITUXIMAB-CHOP IN PRIMARY MEDIASTINAL LARGE B-CELL LYMPHOMA","authors":"T. Vassilakopoulos, Z. Mellios, G. Papageorgiou, A. Piperidou, E. Verigou, C. Chatzidimitriou, C. Kalpadakis, E. Katodritou, H. Giatra, V. Xanthopoulos, G. Gainaru, E. Vrakidou, T. Leonidopoulou, M. Kotsopoulou, M. Palassopoulou, S. Karakatsanis, M. Tsirogianni, E. Hatzimichael, E. Terpos, P. Zikos, C. Poziopoulos, E. Vervessou, M. Arapaki, A. Kopsaftopoulou, A. Liaskas, P. Katsaouni, J. Assimakopoulos, G. Kourti, D. Koutsiafes, M. Siakantaris, G. Karianakis, A. Symeonidis, D. Grentzelias, V. Pappa, P. Tsirigotis, E. Papadaki, E. Plata, M. Bakiri, G. Pangalis, M. Angelopoulou, M. Bouzani","doi":"10.1002/hon.70094_346","DOIUrl":"https://doi.org/10.1002/hon.70094_346","url":null,"abstract":"<p><b>Background:</b> Further to the impressive phase 2 NCI results, retrospective comparisons have shown a modest, non-significant benefit in disease control and a reduced need for consolidative radiotherapy (RT) with R-da-EPOCH versus R-CHOP in PMLBCL. However, the numbers of patients were small-to-moderate (<< 100) and the choice of treatment was at the discretion of the treating physician, inevitably introducing systematic bias.</p><p><b>Aims:</b> To evaluate the efficacy of R-da-EPOCH versus R-CHOP with an -as much as possible- unbiased selection of control group patients</p><p><b>Methods:</b> R-da-EPOCH was adopted in all consecutive patients with PMLBCL ≤ 65 years (<i>n</i> = 156) in 18 participating Centers, which were providing R-CHOP as standard of care until that time. The control group of R-CHOP-treated patients was devised from the same Centers’ database, selecting in chronological order (most recent first) an equal number of consecutive patients to those treated with R-da-EPOCH at the same Center, if possible, thus minimizing selection bias. Due to lack of some appropriate controls in a few Centers (< 20 R-CHOP-treated patients less), they were substituted by consecutive patients treated in few of the other centers, which had comparable potential (large or small, public or private centers). R-CHOP-14 was given in 22/156 patients of the control group (14%).</p><p><b>Results:</b> The groups of R-da-EPOCH (<i>n</i> = 156) and R-CHOP-treated patients (<i>n</i> = 156) were absolutely comparable in terms of patients’ characteristics except for more frequent multiple extranodal involvement in R-CHOP (8.4% vs. 16.0%, <i>p</i> = 0.042). The 5-year freedom from progression (FFP), event-free survival (EFS) and overall survival (OS) rates for R-da-EPOCH versus R-CHOP were 87.5% versus 75.5% (<i>p</i> = 0.011), 84.4% versus 75.5% (<i>p</i> = 0.052 counting 4 t-AML cases after R-da-EPOCH as events) and 94.1% versus 86.9% (<i>p</i> = 0.039). Among patients potentially eligible for RT (no progressive disease), RT was administered to 10% versus 70% after R-da-EPOCH or R-CHOP. In multivariate analysis, after adjustment for age, gender, multiple extranodal sites and recently published prognostic models (extranodal and LDH > 2x or bulk) the difference between R-da-EPOCH and R-CHOP remained significant regarding FFP, OS and EFS, when the extranodal-LDH model was assessed, but only for FFP when the extranodal-bulk model was taken into account (0.10 < <i>p</i> < 0.20 for EFS and OS). Only 77 (58%) of 133 patients with currently available data had absolute adherence to R-da-EPOCH protocol, reflecting the real-life situation. These patients had a 5-year FFP of 90.9% and 85.1% (<i>p</i> = 0.30).</p><p><b>Conclusion:</b> Our non-randomized, comparative study is by far the largest one comparing R-da-EPOCH versus R-CHOP and carried the least possible systematic error in the retrospective setting. R-da-EPOCH minimized the need of RT and demonst","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.70094_346","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300391","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}
J. M. Zaucha, E. Paszkiewicz-Kozik, M. Taszner, B. Małkowski, J. Rybka, K. Chromik, A. Kołkowska-Leśniak, E. Subocz, Ł. Targoński, P. Ceklarz, M. Witkowska, K. Domańska-Czyż, A. Giza, R. Swoboda, M. Kobylecka, C. Voltin, J. Romejko-Jarosińska, M. Świerkowska, B. Ostrowska, A. Druzd-Sitek, M. Kurlapski, M. Bednarek, G. Romanowicz, J. Góra-Tybor, J. Hałka, T. Wróbel, S. Giebel, G. Helbig, E. Lech-Marańda
<p><b>Introduction</b>: Achieving complete metabolic remission (CMR) before autologous hematopoietic cell transplantation aHCT in patients with relapsed/refractory (r/r) classical Hodgkin Lymphoma patients (pts) improves their long-term outcomes. BGD (bendamustine, gemcitabine, dexamethasone) in a second line induces CMR in about 70% of r/r HL pts (Paszkiewicz-Kozik et al., <i>Hematological Oncology</i>, 42, Suppl, p364 2023). The phase 2 N-BURGUND trial (EudraCT 2021-002630-17) evaluates the efficacy and safety of a very short course of Nivolumab (N) (3 cycles) followed by 2 (up to maximum 4) cycles of BGD in r/r HL pts before aHCT <i>having hypothesized</i> that addition of Nx3 will improve the response to BGD (CMR) by 15%. Here, we present the efficacy and safety results of the enrolled patients.</p><p><b>Methods:</b> Patients aged ≥ 18 years with r/r advanced stage (IIB-IV) HL after first-line treatment were eligible and received N 240 mg IV Q2W for three cycles followed by PET<sub>NIV</sub> and 2 to max four cycles of BGD (bendamustine 90 mg/m<sup>2</sup> D1,2; gemcitabine 800 mg/m<sup>2</sup> on D1,4; dexamethasone 40 mg on D1–4) combined with CD34+ cell mobilization followed by PET<sub>2BGD</sub>. Patients achieving CMR (Deauville score 1–3 assessed by the Central Reviewer Panel) are subjected to aHCT. The primary endpoint for this analysis is centrally assessed PET<sub>BGD</sub>-negativity response in patients after two cycles of BGD. The secondary endpoints are PET<sub>NIVO</sub> response and the results of circulating tumor DNA assessment at the time of PET examinations.</p><p><b>Results</b>: Between December 2022 and November 2024, 86 pts (50% females) with r/r cHL were enrolled from 9 centers affiliated with the PLRG. Median (range) age was 36 years (20–71); 71 (83%) patients received ABVD, 2 (2%) BV+AVD, and 13 (15%) BEACOPPesc in the first line. Forty pts (47%) were primary refractory, including 6 to BEACOPPesc and 2 to BV+AVD; twenty-five (29%) pts had an early relapse (< 12 months), whereas the remaining 21 (24%) had a late relapse. All patients have completed 3 × N and 2 × BGD. Eighty-four PET<sub>NIVO,</sub> and 78 PET<sub>BGD</sub> results were available at the time of submission. The PET<sub>NIVO</sub> negativity rate was 34%. Afterward, the PET<sub>BGD</sub> negativity rate increased to 86%. In 76 pts with two PET assessments available, BGD improved response in 37 (48%) pts. One patient required two more BGD cycles to achieve CMR. Grade ≥ 3 adverse events (AEs) (26.5% of all AEs) occurred in 13 pts (22% of all pts). Drug-related grade 4 AEs included flare syndrome and anemia caused by pure red cell aplasia, which resolved after 6 months of treatment with steroids, rituximab, and bortezomib. Immune-mediated AEs (3,6% of all AEs) occurred in 5% of patients who received nivolumab. The most common AE was rash (14.5%) (Figure 1). There were no deaths during the study.</p><p><b>Conclusion:</b> A very short Nivolumab induction fo
{"title":"A SHORT (x3) NIVOLUMAB BEFORE BGD CHEMOTHERAPY IMPROVES THE REMISSION RATE IN RELAPSED/REFRACTORY HODGKIN LYMPHOMA: N-BURGUND TRIAL OF THE POLISH LYMPHOMA RESEARCH GROUP","authors":"J. M. Zaucha, E. Paszkiewicz-Kozik, M. Taszner, B. Małkowski, J. Rybka, K. Chromik, A. Kołkowska-Leśniak, E. Subocz, Ł. Targoński, P. Ceklarz, M. Witkowska, K. Domańska-Czyż, A. Giza, R. Swoboda, M. Kobylecka, C. Voltin, J. Romejko-Jarosińska, M. Świerkowska, B. Ostrowska, A. Druzd-Sitek, M. Kurlapski, M. Bednarek, G. Romanowicz, J. Góra-Tybor, J. Hałka, T. Wróbel, S. Giebel, G. Helbig, E. Lech-Marańda","doi":"10.1002/hon.70094_357","DOIUrl":"https://doi.org/10.1002/hon.70094_357","url":null,"abstract":"<p><b>Introduction</b>: Achieving complete metabolic remission (CMR) before autologous hematopoietic cell transplantation aHCT in patients with relapsed/refractory (r/r) classical Hodgkin Lymphoma patients (pts) improves their long-term outcomes. BGD (bendamustine, gemcitabine, dexamethasone) in a second line induces CMR in about 70% of r/r HL pts (Paszkiewicz-Kozik et al., <i>Hematological Oncology</i>, 42, Suppl, p364 2023). The phase 2 N-BURGUND trial (EudraCT 2021-002630-17) evaluates the efficacy and safety of a very short course of Nivolumab (N) (3 cycles) followed by 2 (up to maximum 4) cycles of BGD in r/r HL pts before aHCT <i>having hypothesized</i> that addition of Nx3 will improve the response to BGD (CMR) by 15%. Here, we present the efficacy and safety results of the enrolled patients.</p><p><b>Methods:</b> Patients aged ≥ 18 years with r/r advanced stage (IIB-IV) HL after first-line treatment were eligible and received N 240 mg IV Q2W for three cycles followed by PET<sub>NIV</sub> and 2 to max four cycles of BGD (bendamustine 90 mg/m<sup>2</sup> D1,2; gemcitabine 800 mg/m<sup>2</sup> on D1,4; dexamethasone 40 mg on D1–4) combined with CD34+ cell mobilization followed by PET<sub>2BGD</sub>. Patients achieving CMR (Deauville score 1–3 assessed by the Central Reviewer Panel) are subjected to aHCT. The primary endpoint for this analysis is centrally assessed PET<sub>BGD</sub>-negativity response in patients after two cycles of BGD. The secondary endpoints are PET<sub>NIVO</sub> response and the results of circulating tumor DNA assessment at the time of PET examinations.</p><p><b>Results</b>: Between December 2022 and November 2024, 86 pts (50% females) with r/r cHL were enrolled from 9 centers affiliated with the PLRG. Median (range) age was 36 years (20–71); 71 (83%) patients received ABVD, 2 (2%) BV+AVD, and 13 (15%) BEACOPPesc in the first line. Forty pts (47%) were primary refractory, including 6 to BEACOPPesc and 2 to BV+AVD; twenty-five (29%) pts had an early relapse (< 12 months), whereas the remaining 21 (24%) had a late relapse. All patients have completed 3 × N and 2 × BGD. Eighty-four PET<sub>NIVO,</sub> and 78 PET<sub>BGD</sub> results were available at the time of submission. The PET<sub>NIVO</sub> negativity rate was 34%. Afterward, the PET<sub>BGD</sub> negativity rate increased to 86%. In 76 pts with two PET assessments available, BGD improved response in 37 (48%) pts. One patient required two more BGD cycles to achieve CMR. Grade ≥ 3 adverse events (AEs) (26.5% of all AEs) occurred in 13 pts (22% of all pts). Drug-related grade 4 AEs included flare syndrome and anemia caused by pure red cell aplasia, which resolved after 6 months of treatment with steroids, rituximab, and bortezomib. Immune-mediated AEs (3,6% of all AEs) occurred in 5% of patients who received nivolumab. The most common AE was rash (14.5%) (Figure 1). There were no deaths during the study.</p><p><b>Conclusion:</b> A very short Nivolumab induction fo","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.70094_357","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300335","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. Suleman, K. Roos, K. Mangoff, Y. Jiang, G. Klein, D. Villa, D. MacDonald, M. Aljama, M. Shafey, N. Forward, J. Larouche, A. Nikonova, M. Sebag, I. Sandhu, S. Chow, R. McClure, M. Gallucci, H. Simmons, G. Tomlinson, N. L. Berinstein
Background: An optimal first-line therapy for Waldenstrom’s Macroglobulinemia (WM) has not been defined. We postulated that combining bendamustine and rituximab (BR) with acalabrutinib will result in deep and durable responses, particularly in high-risk patient subsets.
Methods: The BRAWM clinical trial (NCT04624906) combined BR and acalabrutinib in a one-year, fixed duration treatment course of six 28-day cycles of BR and 365 days of concurrent acalabrutinib. This phase II trial took place at 9 clinical sites across Canada. The primary outcome was combined complete response + very good partial response (CR+VGPR) rate, and secondary outcomes included PFS, OS and Measurable Residual Disease (MRD). Outcomes were assessed for all participants, and for high-risk subsets (MYD88WT, CXCR4MUT and TP53MUT). MRD analyses uses bone marrow (BM) and peripheral blood (PB) samples collected at trial specific time points, assessments being performed by Adaptive Biotechnologies (Seattle, USA) using the clonoSEQ assay. Outcomes were compared between high-risk and non-high risk subsets.
Results: This trial enrolled 63 participants. The median age was 69 years (range 39–85), and 49 (78%) were male, 38% intermediate-risk and 51% high-risk IPSS-WM score. Mutational analysis in 57 participants showed 50 (88%) were MYD88MUT and 16 (30%) were CXCR4MUT, 1 was TP53MUT. CR+VGPR occurred in 37/59 participants (62.7%) at cycle 7, 28/45 (62.2%) at cycle 12, and 21/39 (53.8%) at month 18 (Figure 1A). The median follow-up was 18 months (1.4–42.4). Both 24-month OS and PFS were 97.6% (95% CI: 93%–100%), 1 participant died at 15 months unrelated to treatment. On univariate analysis, CXCR4MUT was not associated with inferior CR+VGPR rate at 1 year (p = 0.10). Grade 3/4 treatment-related adverse events (TRAE) occurred in 31/63 participants during combination therapy, most common being neutropenia (n = 23) and thrombocytopenia (n = 3). During monotherapy, 13/59 participants had a grade 3/4 TRAE, 6 of whom had neutropenia. MRD negativity (threshold of 10−6) in PB was 82% at cycle 7, 91% at cycle 12 and 71% at month 18. MRD negativity in BM was not as frequent but increased in BM over time (9% at cycle 7, 12% at cycle 12 and 23% at month 18). MRD negativity rates at cycles 7 and 12 were similar in those with and without CXCR4MUT and MYD88WT (Figure 1B). Log reductions of MRD in PB and BM in high-risk subsets were also comparable to corresponding non-high risk subsets.
Conclusions: Fixed duration BR and acalabrutinib was effective and well-tolerated. This regimen achieves amongst the highest CR+VGPR rates seen in frontline WM trials. Acknowledging sample size limitations, high-risk sub
{"title":"FIXED DURATION TREATMENT OF BENDAMUSTINE-RITUXIMAB AND ACALABRUTINIB IN FRONTLINE WALDENSTROM’S MACROGLOBULINEMIA: DEEP MOLECULAR RESPONSES IN HIGH-RISK PATIENT SUBSETS","authors":"A. Suleman, K. Roos, K. Mangoff, Y. Jiang, G. Klein, D. Villa, D. MacDonald, M. Aljama, M. Shafey, N. Forward, J. Larouche, A. Nikonova, M. Sebag, I. Sandhu, S. Chow, R. McClure, M. Gallucci, H. Simmons, G. Tomlinson, N. L. Berinstein","doi":"10.1002/hon.70093_54","DOIUrl":"https://doi.org/10.1002/hon.70093_54","url":null,"abstract":"<p><b>Background:</b> An optimal first-line therapy for Waldenstrom’s Macroglobulinemia (WM) has not been defined. We postulated that combining bendamustine and rituximab (BR) with acalabrutinib will result in deep and durable responses, particularly in high-risk patient subsets.</p><p><b>Methods:</b> The BRAWM clinical trial (NCT04624906) combined BR and acalabrutinib in a one-year, fixed duration treatment course of six 28-day cycles of BR and 365 days of concurrent acalabrutinib. This phase II trial took place at 9 clinical sites across Canada. The primary outcome was combined complete response + very good partial response (CR+VGPR) rate, and secondary outcomes included PFS, OS and Measurable Residual Disease (MRD). Outcomes were assessed for all participants, and for high-risk subsets (<i>MYD88</i><sup><i>WT</i></sup><i>, CXCR4</i><sup><i>MUT</i></sup> and <i>TP53</i><sup><i>MUT</i></sup>). MRD analyses uses bone marrow (BM) and peripheral blood (PB) samples collected at trial specific time points, assessments being performed by Adaptive Biotechnologies (Seattle, USA) using the clonoSEQ assay. Outcomes were compared between high-risk and non-high risk subsets.</p><p><b>Results:</b> This trial enrolled 63 participants. The median age was 69 years (range 39–85), and 49 (78%) were male, 38% intermediate-risk and 51% high-risk IPSS-WM score. Mutational analysis in 57 participants showed 50 (88%) were <i>MYD88</i><sup><i>MUT</i></sup> and 16 (30%) were <i>CXCR4</i><sup><i>MUT</i></sup>, 1 was <i>TP53</i> <sup><i>MUT</i></sup>. CR+VGPR occurred in 37/59 participants (62.7%) at cycle 7, 28/45 (62.2%) at cycle 12, and 21/39 (53.8%) at month 18 (Figure 1A). The median follow-up was 18 months (1.4–42.4). Both 24-month OS and PFS were 97.6% (95% CI: 93%–100%), 1 participant died at 15 months unrelated to treatment. On univariate analysis, <i>CXCR4</i><sup><i>MUT</i></sup> was not associated with inferior CR+VGPR rate at 1 year (<i>p</i> = 0.10). Grade 3/4 treatment-related adverse events (TRAE) occurred in 31/63 participants during combination therapy, most common being neutropenia (<i>n</i> = 23) and thrombocytopenia (<i>n</i> = 3). During monotherapy, 13/59 participants had a grade 3/4 TRAE, 6 of whom had neutropenia. MRD negativity (threshold of 10<sup>−6</sup>) in PB was 82% at cycle 7, 91% at cycle 12 and 71% at month 18. MRD negativity in BM was not as frequent but increased in BM over time (9% at cycle 7, 12% at cycle 12 and 23% at month 18). MRD negativity rates at cycles 7 and 12 were similar in those with and without <i>CXCR4</i><sup><i>MUT</i></sup> and <i>MYD88</i><sup><i>WT</i></sup> (Figure 1B). Log reductions of MRD in PB and BM in high-risk subsets were also comparable to corresponding non-high risk subsets.</p><p><b>Conclusions:</b> Fixed duration BR and acalabrutinib was effective and well-tolerated. This regimen achieves amongst the highest CR+VGPR rates seen in frontline WM trials. Acknowledging sample size limitations, high-risk sub","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_54","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300397","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}
The Organizing Committee of the Lugano Classification Workshop
In the decade since publication of the Lugano Classification (Cheson et al, J Clin Oncol 2014,32:3059–3068; Barrington et al, J Clin Oncol 2014, 32:3048–3058), major advances in lymphoma therapy and assessment, including metabolic tumor volume (MTV) and circulating tumor DNA (ctDNA) prompted a workshop at the International Conference on Malignant Lymphoma-17 entitled “Lugano Classification: Looking Toward the Future”, to determine whether a revision was warranted and what it should look like. This report summarizes the conclusions of that workshop and a subsequent questionnaire of the participants. It was concluded that, whereas, minor modifications could be made now, the current classification should remain the standard until the clinical benefit of MTV and ctDNA are firmly established and practical considerations demonstrated. An ICML sponsored standing committee will monitor progress and ensure that a revision of the Lugano Classification will be proposed when warranted.
自Lugano分类发表以来的十年(Cheson et al ., journal clinical oncology, 2014,32:3059 - 3068；Barrington等，J clinical oncology, 2014, 32:3048-3058)，淋巴瘤治疗和评估的重大进展，包括代谢肿瘤体积（MTV）和循环肿瘤DNA (ctDNA)，促使恶性淋巴瘤国际会议-17召开了题为“Lugano分类：展望未来”的研讨会，以确定是否有必要进行修订，以及修订应该是什么样子。本报告总结了该讲习班的结论和随后与会者的调查表。结论是，尽管现在可以进行微小的修改，但在MTV和ctDNA的临床益处得到牢固确立和实际考虑得到证实之前，目前的分类仍应保持标准。由ICML赞助的常设委员会将监测进展情况，并确保在必要时提出修订卢加诺分类的建议。
{"title":"Current Status of Revisions to the Lugano Classification in Lymphoma","authors":"The Organizing Committee of the Lugano Classification Workshop","doi":"10.1002/hon.70103","DOIUrl":"https://doi.org/10.1002/hon.70103","url":null,"abstract":"<p>In the decade since publication of the Lugano Classification (Cheson et al, J Clin Oncol 2014,32:3059–3068; Barrington et al, J Clin Oncol 2014, 32:3048–3058), major advances in lymphoma therapy and assessment, including metabolic tumor volume (MTV) and circulating tumor DNA (ctDNA) prompted a workshop at the International Conference on Malignant Lymphoma-17 entitled “Lugano Classification: Looking Toward the Future”, to determine whether a revision was warranted and what it should look like. This report summarizes the conclusions of that workshop and a subsequent questionnaire of the participants. It was concluded that, whereas, minor modifications could be made now, the current classification should remain the standard until the clinical benefit of MTV and ctDNA are firmly established and practical considerations demonstrated. An ICML sponsored standing committee will monitor progress and ensure that a revision of the Lugano Classification will be proposed when warranted.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 4","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.70103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300393","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. Martynchyck, G. Chong, A. Barraclough, S. Ratnasingam, T. Marconi, J. B. Palmer, C. Keane, S. T. B. Lee, A. M. Scott, A. Romano, L. Churilov, D. Lee, E. A. Hawkes
Background: Standard rituximab (R) +lenalidomide (R2) or chemoimmunotherapy is effective in treatment-naïve follicular lymphoma (TN FL) but is associated with Grade 3–4 AE rates > 65% with elderly patients (pts) overrepresented. Golcadomide (Golca) is a potent first-in-class oral Cereblon E3 Ligase Modulator (CELMoD) with dual immunomodulatory and anti-tumor activity 10- to 100-fold enhanced compared to lenalidomide, preferential lymphoid organ distribution and a favourable toxicity profile (Chavez ASH 2024; Amzallag ASH 2024). R-Golca yields responses in 93% relapsed FL. We have demonstrated immune augmentation, safety and efficacy of PD1/PDL1i nivolumab (N) +rituximab, and atezolizumab-obinutuzumab-radiotherapy in TN FL (Chong ASCO 2024; Barraclough Blood Adv 2025). We describe here the interim analysis of a randomised phase II study of R-Golca +/- N in stage II-IV, Grade 1–3A TN FL. (Chong ASCO 2024)
Methods: TOP-FLOR (NCT05788081) is an investigator-led multicentre randomised open label umbrella Baysian Optimal Phase II trial in TN FL. Up to 40pts will be randomised 1:1 to receive 8 cycles of induction therapy Q4W: R (375 mg/m2 IV, D1), Golca (0.4 mg p.o daily, D1–14) +/- N (480 mg IV, D1) and 2 years of R maintenance (Q12W). The primary endpoint is rate of Complete Metabolic Response (CMR) in the absence of cessation due to prohibitive toxicity (CTCAE V5.0) following induction. Interim efficacy analysis (PET/CT Lugano response) in the first 22 pts was pre-planned, with a predefined futility threshold of 7/11 CMR (63.6%) in each arm.
Results: The interim analysis included 22 enrolled pts (11 per arm). Median age was 64.5y (range 49–77) with 68% male. CMR rate at the end of induction was 82% (18/22; 95% CI: 60%, 95%), CMR rate by arm in the futility cohort, was: 10/11 (92%) R-Golca and 8/11 (73%) R-Golca+N with 1 permanently ceasing due to Gr4 sepsis in cycle 1, unrelated to therapy and 1 ceasing due to disease progression (Figure 1). Proportion of pts experiencing an AE during induction were: 100% Gr1, 82% Gr2, 64% Gr3, 9% Gr4 (2pt). Most frequent of any grade were infection (77%; 95% CI: 54%–92% [Gr3 14%]), neutrophil count decrease (63%; 95% CI: 40–82% [Gr3+ 92%; plus 2 pt Gr3 febrile neutropenia]; 10pts received G-CSF) and maculo-papular rash (45%; 95% CI: 24%–67%—all in pts who had bactrim & allopurinol which resolved on cessation of allopurinol); 2 pts R-Golca +N arm and 1 pt in the R-Golca arm had Golca dose reduction to 0.3 mg due to adverse events. 18/22 remain on treatment. Interim results reached the threshold for continued recruitment in both arms.
Conclusions: This is the first study to demonstrate that Rituximab-golcadomide +/-nivolumab is a highly effective combination therapy in TN FL with manageable toxicity, most commonly neutropenia and infection. Differences between arms could not be elucidated in this preplanned interim analysis. The study continues recruit
{"title":"TREATMENT OF NEWLY-DIAGNOSED FOLLICULAR LYMPHOMA WITH RITUXIMAB, GOLCADOMIDE +/- NIVOLUMAB- INTERIM ANALYSIS OF THE PHASE II TOP-FLOR STUDY","authors":"A. Martynchyck, G. Chong, A. Barraclough, S. Ratnasingam, T. Marconi, J. B. Palmer, C. Keane, S. T. B. Lee, A. M. Scott, A. Romano, L. Churilov, D. Lee, E. A. Hawkes","doi":"10.1002/hon.70094_230","DOIUrl":"https://doi.org/10.1002/hon.70094_230","url":null,"abstract":"<p><b>Background:</b> Standard rituximab (R) +lenalidomide (R2) or chemoimmunotherapy is effective in treatment-naïve follicular lymphoma (TN FL) but is associated with Grade 3–4 AE rates > 65% with elderly patients (pts) overrepresented. Golcadomide (Golca) is a potent first-in-class oral Cereblon E3 Ligase Modulator (CELMoD) with dual immunomodulatory and anti-tumor activity 10- to 100-fold enhanced compared to lenalidomide, preferential lymphoid organ distribution and a favourable toxicity profile (Chavez ASH 2024; Amzallag ASH 2024). R-Golca yields responses in 93% relapsed FL. We have demonstrated immune augmentation, safety and efficacy of PD1/PDL1i nivolumab (N) +rituximab, and atezolizumab-obinutuzumab-radiotherapy in TN FL (Chong ASCO 2024; Barraclough Blood Adv 2025). We describe here the interim analysis of a randomised phase II study of R-Golca +/- N in stage II-IV, Grade 1–3A TN FL. (Chong ASCO 2024)</p><p><b>Methods:</b> TOP-FLOR (NCT05788081) is an investigator-led multicentre randomised open label umbrella Baysian Optimal Phase II trial in TN FL. Up to 40pts will be randomised 1:1 to receive 8 cycles of induction therapy Q4W: R (375 mg/m<sup>2</sup> IV, D1), Golca (0.4 mg p.o daily, D1–14) +/- N (480 mg IV, D1) and 2 years of R maintenance (Q12W). The primary endpoint is rate of Complete Metabolic Response (CMR) in the absence of cessation due to prohibitive toxicity (CTCAE V5.0) following induction. Interim efficacy analysis (PET/CT Lugano response) in the first 22 pts was pre-planned, with a predefined futility threshold of 7/11 CMR (63.6%) in each arm.</p><p><b>Results:</b> The interim analysis included 22 enrolled pts (11 per arm). Median age was 64.5y (range 49–77) with 68% male. CMR rate at the end of induction was 82% (18/22; 95% CI: 60%, 95%), CMR rate by arm in the futility cohort, was: 10/11 (92%) R-Golca and 8/11 (73%) R-Golca+N with 1 permanently ceasing due to Gr4 sepsis in cycle 1, unrelated to therapy and 1 ceasing due to disease progression (Figure 1). Proportion of pts experiencing an AE during induction were: 100% Gr1, 82% Gr2, 64% Gr3, 9% Gr4 (2pt). Most frequent of any grade were infection (77%; 95% CI: 54%–92% [Gr3 14%]), neutrophil count decrease (63%; 95% CI: 40–82% [Gr3+ 92%; plus 2 pt Gr3 febrile neutropenia]; 10pts received G-CSF) and maculo-papular rash (45%; 95% CI: 24%–67%—all in pts who had bactrim & allopurinol which resolved on cessation of allopurinol); 2 pts R-Golca +N arm and 1 pt in the R-Golca arm had Golca dose reduction to 0.3 mg due to adverse events. 18/22 remain on treatment. Interim results reached the threshold for continued recruitment in both arms.</p><p><b>Conclusions:</b> This is the first study to demonstrate that Rituximab-golcadomide +/-nivolumab is a highly effective combination therapy in TN FL with manageable toxicity, most commonly neutropenia and infection. Differences between arms could not be elucidated in this preplanned interim analysis. The study continues recruit","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.70094_230","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300392","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}
K. M. Linton, J. M. Vose, W. Jurczak, P. J. Lugtenburg, E. Gyan, J. C. Chavez, A. Sureda, J. H. Christensen, H. Tilly, R. Córdoba, D. J. Lewis, M. Hutchings, M. Roost Clausen, J. Sancho, T. Cochrane, S. Leppä, M. E. D. Chamuleau, C. Thieblemont, P. F. Caimi, Y. H. Karimi, C. Andreadis, K. Izutsu, N. Fukuhara, E. Favaro, P. Patah, M. Geybels, I. Altintaş, C. Morehouse, U. Vitolo
<p><b>Introduction:</b> Epcoritamab (epcor), a subcutaneous (SC) CD3xCD20 bispecific antibody, is approved for relapsed/refractory (R/R) follicular lymphoma (FL) after ≥ 2 prior lines of therapy (3L+) based on EPCORE NHL-1 FL (NCT03625037; US/EU; Linton KM, et al. <i>Lancet Haem</i> 2024;11:E593–E605) and NHL-3 FL (NCT04542824; Japan) expansion cohorts (EXP) results. NHL-1 cycle (C) 1 optimization cohort (OPT) implemented a 3-step-up dosing (3-SUD) regimen to support outpatient utilization of epcor in FL. We report 3-y follow-up (FU) from EXP and updated OPT results for epcor monotherapy in patients (pts) with 3L+ FL.</p><p><b>Methods:</b> Pts with CD20+ R/R FL grade[G] 1–3A and ≥ 2 prior lines of systemic treatment (tx) received SC epcor in 28-d Cs until disease progression or unacceptable toxicity. NHL-1 (<i>N</i> = 128) and NHL-3 (<i>N</i> = 21) EXP were pooled for diversity; OPT is reported separately. For EXP, the primary endpoint was efficacy; secondary endpoints were minimal residual disease (ClonoSeq®) negativity and safety. Due to the disproportionate impact of COVID-19 pandemic on pts from EXP, sensitivity analyses with conservative adjustment for COVID-19 deaths were conducted for efficacy. For OPT, the primary endpoint was incidence and severity of cytokine release syndrome (CRS); secondary endpoints were response rates and safety.</p><p><b>Results:</b> As of Dec 2024, median FU was 35 mo and 15.5 mo and median duration of tx was 9.7 mo and 11.4 mo in EXP(<i>N</i> = 149) and OPT(<i>N</i> = 86), respectively. Across cohorts, pts were heavily pretreated (median 3 prior lines) and had high-risk R/R FL features. In the pooled EXP, overall response rate (ORR) was 84.6% and complete response rate (CRR) was 67.1% (Table).</p><p>With longer-term FU, safety from EXP was generally consistent with previous reports. In EXP, conducted during the COVID-19 pandemic peak, 34.9% of pts had G3–4 infections (18.1% COVID-19) and 7.4% had G5 events (5.4% COVID-19). 28% of pts discontinued (d/c) tx due to tx-emergent adverse events (TEAEs; 12.1% COVID-19). G3 or higher infections were reported in 14.3% of pts on ≥ 2y of tx (<i>n</i> = 35).</p><p>In OPT, updated ORR/CRR were 91.9%/73.3%; time-to-event endpoint data were still maturing, with most pts alive (93%).</p><p>With additional FU, safety from OPT remained unchanged from prior reports of only low-grade CRS (39.5% G1 and 9.3% G2) and no immune effector cell-associated neurotoxicity syndrome (ICANS). In OPT, conducted post COVID-19 pandemic peak, 20.9% of pts had G3–4 infections (7.0% COVID-19, all G3); 1 pt had G5 TEAE of viral respiratory tract infection. TEAEs leading to tx d/c occurred in 11% (1.2% COVID).</p><p><b>Conclusions:</b> Epcor monotherapy demonstrated deep and durable responses and manageable safety with no new safety signals at 3y in a large and diversified 3L+ FL global population. OPT cohort results show response rates consistent with those in EXP and confirm the favorable safety profi
{"title":"EPCORITAMAB MONOTHERAPY DEMONSTRATES DEEP AND DURABLE RESPONSES AT 3-YEAR FOLLOW-UP IN PATIENTS WITH RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA","authors":"K. M. Linton, J. M. Vose, W. Jurczak, P. J. Lugtenburg, E. Gyan, J. C. Chavez, A. Sureda, J. H. Christensen, H. Tilly, R. Córdoba, D. J. Lewis, M. Hutchings, M. Roost Clausen, J. Sancho, T. Cochrane, S. Leppä, M. E. D. Chamuleau, C. Thieblemont, P. F. Caimi, Y. H. Karimi, C. Andreadis, K. Izutsu, N. Fukuhara, E. Favaro, P. Patah, M. Geybels, I. Altintaş, C. Morehouse, U. Vitolo","doi":"10.1002/hon.70094_240","DOIUrl":"https://doi.org/10.1002/hon.70094_240","url":null,"abstract":"<p><b>Introduction:</b> Epcoritamab (epcor), a subcutaneous (SC) CD3xCD20 bispecific antibody, is approved for relapsed/refractory (R/R) follicular lymphoma (FL) after ≥ 2 prior lines of therapy (3L+) based on EPCORE NHL-1 FL (NCT03625037; US/EU; Linton KM, et al. <i>Lancet Haem</i> 2024;11:E593–E605) and NHL-3 FL (NCT04542824; Japan) expansion cohorts (EXP) results. NHL-1 cycle (C) 1 optimization cohort (OPT) implemented a 3-step-up dosing (3-SUD) regimen to support outpatient utilization of epcor in FL. We report 3-y follow-up (FU) from EXP and updated OPT results for epcor monotherapy in patients (pts) with 3L+ FL.</p><p><b>Methods:</b> Pts with CD20+ R/R FL grade[G] 1–3A and ≥ 2 prior lines of systemic treatment (tx) received SC epcor in 28-d Cs until disease progression or unacceptable toxicity. NHL-1 (<i>N</i> = 128) and NHL-3 (<i>N</i> = 21) EXP were pooled for diversity; OPT is reported separately. For EXP, the primary endpoint was efficacy; secondary endpoints were minimal residual disease (ClonoSeq®) negativity and safety. Due to the disproportionate impact of COVID-19 pandemic on pts from EXP, sensitivity analyses with conservative adjustment for COVID-19 deaths were conducted for efficacy. For OPT, the primary endpoint was incidence and severity of cytokine release syndrome (CRS); secondary endpoints were response rates and safety.</p><p><b>Results:</b> As of Dec 2024, median FU was 35 mo and 15.5 mo and median duration of tx was 9.7 mo and 11.4 mo in EXP(<i>N</i> = 149) and OPT(<i>N</i> = 86), respectively. Across cohorts, pts were heavily pretreated (median 3 prior lines) and had high-risk R/R FL features. In the pooled EXP, overall response rate (ORR) was 84.6% and complete response rate (CRR) was 67.1% (Table).</p><p>With longer-term FU, safety from EXP was generally consistent with previous reports. In EXP, conducted during the COVID-19 pandemic peak, 34.9% of pts had G3–4 infections (18.1% COVID-19) and 7.4% had G5 events (5.4% COVID-19). 28% of pts discontinued (d/c) tx due to tx-emergent adverse events (TEAEs; 12.1% COVID-19). G3 or higher infections were reported in 14.3% of pts on ≥ 2y of tx (<i>n</i> = 35).</p><p>In OPT, updated ORR/CRR were 91.9%/73.3%; time-to-event endpoint data were still maturing, with most pts alive (93%).</p><p>With additional FU, safety from OPT remained unchanged from prior reports of only low-grade CRS (39.5% G1 and 9.3% G2) and no immune effector cell-associated neurotoxicity syndrome (ICANS). In OPT, conducted post COVID-19 pandemic peak, 20.9% of pts had G3–4 infections (7.0% COVID-19, all G3); 1 pt had G5 TEAE of viral respiratory tract infection. TEAEs leading to tx d/c occurred in 11% (1.2% COVID).</p><p><b>Conclusions:</b> Epcor monotherapy demonstrated deep and durable responses and manageable safety with no new safety signals at 3y in a large and diversified 3L+ FL global population. OPT cohort results show response rates consistent with those in EXP and confirm the favorable safety profi","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.70094_240","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300165","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. 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}
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