Pub Date : 2024-09-27DOI: 10.1016/j.clml.2024.09.010
Somya Khare, Staci Williamson, Brittany O'Barr, Levanto Schachter, Andy Chen, Brandon Hayes-Lattin, Jessica Leonard, Amrita Desai, Peter Ferreira-Gandolfo, Kevin Christmas, Denise Lackey, Richard T Maziarz, Eneida R Nemecek
Background: Chimeric antigen receptor T-cell (CAR-T) therapies are available for patients with Non-Hodgkin Lymphoma (NHL); however, their use has been limited in accessibility due to nondisease factors.
Patients & methods: We conducted a retrospective study evaluating the influence of sociodemographic factors on access and outcomes after CAR-T therapy for adult patients with B-cell NHL in our institution treated between 2016 and 2023.
Results: Among 154 patients treated with CAR-T, 43% were older than 65 years, 68% male, and 14% non-White (including Hispanic). Of those under 65, 66% had private insurance, while 82% over 65 had Medicare. Most patients (85%) were from in-state, 29% from areas below the national poverty level and 18% from nonmetropolitan areas. Distance to the treatment center was greater than 30, 60 or 120 miles for 52%, 40% and 29% of patients, respectively. No significant differences were found in the use of commercial versus investigational products among racial/ethnic minorities or those living >60 miles from the center. However, patients from nonmetropolitan areas and those below the national poverty level were less likely to receive commercial products. With a median follow-up of 11 months, the 1-year overall survival (OS) was 63.2% (95th CI 59.9%-66.8%). Poverty was associated with lower 1-year OS (HR 0.4, 95th CI 0.17-0.90, P = .031).
Conclusion: Our study shows that CAR-T therapy can be delivered across sociodemographic barriers and underscores the importance of considering social determinants of health to optimize access for all patients.
{"title":"Sociodemographic Factors Influencing Access to Chimeric Antigen T-Cell Receptor Therapy for Patients With Non-Hodgkin Lymphoma.","authors":"Somya Khare, Staci Williamson, Brittany O'Barr, Levanto Schachter, Andy Chen, Brandon Hayes-Lattin, Jessica Leonard, Amrita Desai, Peter Ferreira-Gandolfo, Kevin Christmas, Denise Lackey, Richard T Maziarz, Eneida R Nemecek","doi":"10.1016/j.clml.2024.09.010","DOIUrl":"https://doi.org/10.1016/j.clml.2024.09.010","url":null,"abstract":"<p><strong>Background: </strong>Chimeric antigen receptor T-cell (CAR-T) therapies are available for patients with Non-Hodgkin Lymphoma (NHL); however, their use has been limited in accessibility due to nondisease factors.</p><p><strong>Patients & methods: </strong>We conducted a retrospective study evaluating the influence of sociodemographic factors on access and outcomes after CAR-T therapy for adult patients with B-cell NHL in our institution treated between 2016 and 2023.</p><p><strong>Results: </strong>Among 154 patients treated with CAR-T, 43% were older than 65 years, 68% male, and 14% non-White (including Hispanic). Of those under 65, 66% had private insurance, while 82% over 65 had Medicare. Most patients (85%) were from in-state, 29% from areas below the national poverty level and 18% from nonmetropolitan areas. Distance to the treatment center was greater than 30, 60 or 120 miles for 52%, 40% and 29% of patients, respectively. No significant differences were found in the use of commercial versus investigational products among racial/ethnic minorities or those living >60 miles from the center. However, patients from nonmetropolitan areas and those below the national poverty level were less likely to receive commercial products. With a median follow-up of 11 months, the 1-year overall survival (OS) was 63.2% (95<sup>th</sup> CI 59.9%-66.8%). Poverty was associated with lower 1-year OS (HR 0.4, 95<sup>th</sup> CI 0.17-0.90, P = .031).</p><p><strong>Conclusion: </strong>Our study shows that CAR-T therapy can be delivered across sociodemographic barriers and underscores the importance of considering social determinants of health to optimize access for all patients.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-26DOI: 10.1016/j.clml.2024.09.012
Jessica Allen, Diana Abbott, Joy Eskandar, Steven M Bair, Bradley Haverkos, Jagar Jasem, Manali Kamdar, Ajay Major
Background: Short diagnosis-to-treatment interval (DTI) is associated with high-risk disease and poor survival in diffuse large B-cell lymphoma (DLBCL). There is a paucity of literature on DTI and survival in DLBCL treated with first-line DA-R-EPOCH. We hypothesized that rapid initiation of DA-R-EPOCH in aggressive and high-risk DLBCL mitigates the adverse prognostic implication of short DTI.
Patients and methods: We retrospectively examined the association of DTI, categorically (short DTI ≤ 14 and long > 14 days) and continuously, with clinical features and survival outcomes in DLBCL treated with first-line DA-R-EPOCH at our institution.
Results: A total 190 patients were analyzed, 21% with high-grade DLBCL subtypes, 56% IPI ≥ 3, and median DTI of 13 days. The short DTI cohort contained more patients with IPI ≥ 3, bulky disease, and elevated LDH. When analyzed categorically and continuously, DTI was not associated with significant differences in PFS or OS. There was significant multivariable interaction between bulky disease, DTI, and PFS (P = .033), with improved PFS in patients with bulky disease in the short DTI cohort.
Conclusion: We found that negative prognostic implications of DTI are mitigated in DLBCL patients treated with first-line DA-R-EPOCH, suggesting that urgent initiation of DA-R-EPOCH in high-risk DLBCL, including bulky disease, may improve survival. Our study's shorter DTI compared with DTIs reported in prospective DLBCL trials highlights DTI as a marker of external validity in clinical trial results. Future trials should implement protocols encouraging shorter, realistic DTIs to avoid selection bias against high-risk patients who are unable to delay treatment.
{"title":"DA-R-EPOCH May Mitigate the Adverse Prognostic Implication of the Diagnosis-to-Treatment Interval (DTI) in Large B-Cell Lymphomas.","authors":"Jessica Allen, Diana Abbott, Joy Eskandar, Steven M Bair, Bradley Haverkos, Jagar Jasem, Manali Kamdar, Ajay Major","doi":"10.1016/j.clml.2024.09.012","DOIUrl":"https://doi.org/10.1016/j.clml.2024.09.012","url":null,"abstract":"<p><strong>Background: </strong>Short diagnosis-to-treatment interval (DTI) is associated with high-risk disease and poor survival in diffuse large B-cell lymphoma (DLBCL). There is a paucity of literature on DTI and survival in DLBCL treated with first-line DA-R-EPOCH. We hypothesized that rapid initiation of DA-R-EPOCH in aggressive and high-risk DLBCL mitigates the adverse prognostic implication of short DTI.</p><p><strong>Patients and methods: </strong>We retrospectively examined the association of DTI, categorically (short DTI ≤ 14 and long > 14 days) and continuously, with clinical features and survival outcomes in DLBCL treated with first-line DA-R-EPOCH at our institution.</p><p><strong>Results: </strong>A total 190 patients were analyzed, 21% with high-grade DLBCL subtypes, 56% IPI ≥ 3, and median DTI of 13 days. The short DTI cohort contained more patients with IPI ≥ 3, bulky disease, and elevated LDH. When analyzed categorically and continuously, DTI was not associated with significant differences in PFS or OS. There was significant multivariable interaction between bulky disease, DTI, and PFS (P = .033), with improved PFS in patients with bulky disease in the short DTI cohort.</p><p><strong>Conclusion: </strong>We found that negative prognostic implications of DTI are mitigated in DLBCL patients treated with first-line DA-R-EPOCH, suggesting that urgent initiation of DA-R-EPOCH in high-risk DLBCL, including bulky disease, may improve survival. Our study's shorter DTI compared with DTIs reported in prospective DLBCL trials highlights DTI as a marker of external validity in clinical trial results. Future trials should implement protocols encouraging shorter, realistic DTIs to avoid selection bias against high-risk patients who are unable to delay treatment.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-26DOI: 10.1016/j.clml.2024.09.013
Ehab L Atallah, David Wei, Dominick Latremouille-Viau, Carmine Rossi, Andrea Damon, Germano Ferreira, Annie Guérin, Kejal Jadhav
Background: Tyrosine kinase inhibitors (TKIs) are the mainstay treatment for chronic myeloid leukemia in chronic phase (CML-CP). Asciminib, an ABL/BCR::ABL1 inhibitor which binds to the myristoyl pocket, was recently approved in the US for patients with CML-CP previously treated with ≥2 TKIs or with the T315I mutation. This study described treatment patterns and real-world clinical outcomes among patients with CML-CP treated with asciminib in US clinical practice.
Methods: Electronic health record data from adult patients with CML-CP who initiated asciminib after ≥2 prior TKIs, without the T315I mutation, were obtained from the Flatiron Health database. Time-to-treatment discontinuation and molecular response (MR; time-to-BCR::ABL ≤0.1% and time-to-BCR::ABL1 ≤1%, separately) were evaluated from asciminib initiation (index date) using Kaplan-Meier analyses.
Results: Overall, 97 patients initiated asciminib (median age: 63 years, 50.5% female, 64.9% White) after either 2 (47.4%) or 3 (24.7%), or ≥4 (27.8%) prior TKIs. In total, 85.7% and 78.1% of patients remained on asciminib by 12- and 24-weeks postindex, respectively. Among patients with ≥1 MR assessment postindex, 31.3% (95% confidence interval [CI]: 21.6%, 43.9%) and 49.7% (95% CI: 38.1%, 62.6%) achieved or maintained BCR::ABL1 ≤0.1%, while 51.3% (95% CI: 40.1%, 63.6%) and 64.2% (95% CI: 52.6%, 75.6%) achieved or maintained BCR::ABL1 ≤1%, by 12- and 24-weeks, respectively.
Conclusions: Results of this real-world study describing clinical outcomes among patients with CML-CP treated with asciminib after ≥2 prior TKIs in the US demonstrated that asciminib was well-tolerated and effective. These findings were consistent with results from the ASCEMBL trial.
{"title":"Real-World Evaluation of Treatment Patterns and Clinical Outcomes among Patients With Chronic Myeloid Leukemia in Chronic Phase Treated With Asciminib in Clinical Practice in the United States: Real-world asciminib treatment outcomes in CML-CP.","authors":"Ehab L Atallah, David Wei, Dominick Latremouille-Viau, Carmine Rossi, Andrea Damon, Germano Ferreira, Annie Guérin, Kejal Jadhav","doi":"10.1016/j.clml.2024.09.013","DOIUrl":"https://doi.org/10.1016/j.clml.2024.09.013","url":null,"abstract":"<p><strong>Background: </strong>Tyrosine kinase inhibitors (TKIs) are the mainstay treatment for chronic myeloid leukemia in chronic phase (CML-CP). Asciminib, an ABL/BCR::ABL1 inhibitor which binds to the myristoyl pocket, was recently approved in the US for patients with CML-CP previously treated with ≥2 TKIs or with the T315I mutation. This study described treatment patterns and real-world clinical outcomes among patients with CML-CP treated with asciminib in US clinical practice.</p><p><strong>Methods: </strong>Electronic health record data from adult patients with CML-CP who initiated asciminib after ≥2 prior TKIs, without the T315I mutation, were obtained from the Flatiron Health database. Time-to-treatment discontinuation and molecular response (MR; time-to-BCR::ABL ≤0.1% and time-to-BCR::ABL1 ≤1%, separately) were evaluated from asciminib initiation (index date) using Kaplan-Meier analyses.</p><p><strong>Results: </strong>Overall, 97 patients initiated asciminib (median age: 63 years, 50.5% female, 64.9% White) after either 2 (47.4%) or 3 (24.7%), or ≥4 (27.8%) prior TKIs. In total, 85.7% and 78.1% of patients remained on asciminib by 12- and 24-weeks postindex, respectively. Among patients with ≥1 MR assessment postindex, 31.3% (95% confidence interval [CI]: 21.6%, 43.9%) and 49.7% (95% CI: 38.1%, 62.6%) achieved or maintained BCR::ABL1 ≤0.1%, while 51.3% (95% CI: 40.1%, 63.6%) and 64.2% (95% CI: 52.6%, 75.6%) achieved or maintained BCR::ABL1 ≤1%, by 12- and 24-weeks, respectively.</p><p><strong>Conclusions: </strong>Results of this real-world study describing clinical outcomes among patients with CML-CP treated with asciminib after ≥2 prior TKIs in the US demonstrated that asciminib was well-tolerated and effective. These findings were consistent with results from the ASCEMBL trial.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-23DOI: 10.1016/j.clml.2024.09.009
Despina Fotiou, Meletios A Dimopoulos
Multiple myeloma is a challenging hematological malignancy, with ongoing efforts toward finding a cure. Dr. Raymond Alexanian has been instrumental in advancing the understanding and treatment of multiple myeloma through his pioneering research. Trained at Dartmouth College and Harvard Medical School, Dr. Alexanian MD Anderson Cancer Center career spanned nearly 5 decades. He developed the highly effective MP (melphalan-prednisone) regimen, which became a standard treatment for years. Dr. Alexanian's exploration of steroids, particularly high-dose dexamethasone, and the collaboration with Dr. Bart Barlogie led to the development of the VAD (vincristine, doxorubicin, and dexamethasone) regimen, significantly improving outcomes for refractory cases. He also contributed to the establishment of high-dose melphalan with autologous stem cell transplantation. Dr. Alexanian's work identified critical prognostic factors and contributed understanding indolent and localized myeloma. His efforts in evaluating new agents, including thalidomide and bortezomib, further enhanced treatment options. Beyond research, his compassionate patient care and advocacy have had a profound impact. Dr. Alexanian's legacy continues to inspire advancements in multiple myeloma treatment, with his innovative approaches reshaping the field and fostering the pursuit of a cure.
{"title":"Dr. Raymond Alexanian: Pioneering Contributions to Multiple Myeloma Research, Treatment, and the Concept of Curability.","authors":"Despina Fotiou, Meletios A Dimopoulos","doi":"10.1016/j.clml.2024.09.009","DOIUrl":"https://doi.org/10.1016/j.clml.2024.09.009","url":null,"abstract":"<p><p>Multiple myeloma is a challenging hematological malignancy, with ongoing efforts toward finding a cure. Dr. Raymond Alexanian has been instrumental in advancing the understanding and treatment of multiple myeloma through his pioneering research. Trained at Dartmouth College and Harvard Medical School, Dr. Alexanian MD Anderson Cancer Center career spanned nearly 5 decades. He developed the highly effective MP (melphalan-prednisone) regimen, which became a standard treatment for years. Dr. Alexanian's exploration of steroids, particularly high-dose dexamethasone, and the collaboration with Dr. Bart Barlogie led to the development of the VAD (vincristine, doxorubicin, and dexamethasone) regimen, significantly improving outcomes for refractory cases. He also contributed to the establishment of high-dose melphalan with autologous stem cell transplantation. Dr. Alexanian's work identified critical prognostic factors and contributed understanding indolent and localized myeloma. His efforts in evaluating new agents, including thalidomide and bortezomib, further enhanced treatment options. Beyond research, his compassionate patient care and advocacy have had a profound impact. Dr. Alexanian's legacy continues to inspire advancements in multiple myeloma treatment, with his innovative approaches reshaping the field and fostering the pursuit of a cure.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: High risk myeloma is heterogeneous with significant variation in risk stratifications. Real world outcomes differ from controlled clinical trials and affected by socioeconomical determinants.
Material and methods: This retrospective study was performed in a North Indian teriarty care cancer hospital. Out of 384,76(19.7%) high risk myeloma patients (median age 58 years) were analyzed.
Result and conclusion: Most common HRCA was 1 q gain 36(47.4%) followed by del17p 32(42.1%). 61/76(80.2%) received bortezomib based triplets and 15(19.74%) daratumumab based quadruplets induction, 31(40.79%) received ASCT. Median duration of follow up was 19.5 months. The 2 year OS and PFS was 73.8%, 52.6% respectively. Estimated 3 year OS was 74.7% in ASCT cohort versus 52.9% (P = .0067) without. Estimated 3-year PFS in the ASCT cohort was 72.1% versus 30.3% (P = .0026) without. Estimated 3-year OS for single hit and multi hit ultra HRMM was 67.7% and 61.9% (P = .642) whereas PFS was 58.2% and 35.2% (P = .486) respectively. In multivariate analysis ASCT correlated with better OS (HR 0.3, P = .041) and PFS (HR 0.35, P = .012). Absence of baseline renal impairment correlated with better OS (HR 4.12, P = .004) only. Early aggressive therapy with prompt ASCT translates to a better survival in high risk myeloma. Emphasis on real world clinical outcome is the need of the hour for addressing practical issues and improving global myeloma outcome.
{"title":"Real World Outcome of High-Risk Multiple Myeloma: An Indian Tertiary Care Centre Experience.","authors":"Anveshika Soni, Sujay Rainchwar, Reema Singh, Dikshat Gopal Gupta, Nakul Tikare, Rohan Halder, Roy J Palatty, Vipul Sharad Sheth, Narendra Agrawal, Dinesh Bhurani, Tribikram Panda","doi":"10.1016/j.clml.2024.09.007","DOIUrl":"https://doi.org/10.1016/j.clml.2024.09.007","url":null,"abstract":"<p><strong>Introduction: </strong>High risk myeloma is heterogeneous with significant variation in risk stratifications. Real world outcomes differ from controlled clinical trials and affected by socioeconomical determinants.</p><p><strong>Material and methods: </strong>This retrospective study was performed in a North Indian teriarty care cancer hospital. Out of 384,76(19.7%) high risk myeloma patients (median age 58 years) were analyzed.</p><p><strong>Result and conclusion: </strong>Most common HRCA was 1 q gain 36(47.4%) followed by del17p 32(42.1%). 61/76(80.2%) received bortezomib based triplets and 15(19.74%) daratumumab based quadruplets induction, 31(40.79%) received ASCT. Median duration of follow up was 19.5 months. The 2 year OS and PFS was 73.8%, 52.6% respectively. Estimated 3 year OS was 74.7% in ASCT cohort versus 52.9% (P = .0067) without. Estimated 3-year PFS in the ASCT cohort was 72.1% versus 30.3% (P = .0026) without. Estimated 3-year OS for single hit and multi hit ultra HRMM was 67.7% and 61.9% (P = .642) whereas PFS was 58.2% and 35.2% (P = .486) respectively. In multivariate analysis ASCT correlated with better OS (HR 0.3, P = .041) and PFS (HR 0.35, P = .012). Absence of baseline renal impairment correlated with better OS (HR 4.12, P = .004) only. Early aggressive therapy with prompt ASCT translates to a better survival in high risk myeloma. Emphasis on real world clinical outcome is the need of the hour for addressing practical issues and improving global myeloma outcome.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-21DOI: 10.1016/j.clml.2024.09.008
Bruno Almeida Costa, Thomaz Alexandre Costa, Gabriel Cavalcante Lima Chagas, Tarek H Mouhieddine, Joshua Richter, Saad Z Usmani, Sham Mailankody, Sridevi Rajeeve, Hamza Hashmi
Background: The efficacy of elotuzumab, an anti-SLAMF7 monoclonal antibody, in treating relapsed/refractory multiple myeloma (RRMM) and newly-diagnosed multiple myeloma (NDMM) has varied in randomized controlled trials (RCTs). Moreover, there is limited data on its real-world application.
Patients and methods: We conducted a systematic review and meta-analysis of RCTs investigating the addition of elotuzumab to backbone antimyeloma regimens. The primary outcome of interest was progression-free survival (PFS). Secondary efficacy outcomes included overall survival (OS), overall response rate (ORR), and rates of very good partial response or better (VGPR). Key toxicities were also evaluated.
Results: Three RRMM trials (n = 915) and 5 NDMM trials (n = 1790) were included, with 50% of the 2705 patients receiving elotuzumab-containing triplets or quadruplets. In RRMM settings, elotuzumab use significantly improved PFS (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.60-0.82; P < .001; I² = 0%). This benefit was consistent among patients with high-risk cytogenetics (HR, 0.62; 95% CI, 0.43-0.90; P = .01; I² = 0%) and was particularly evident in those previously treated with proteasome inhibitors (PIs) or immunomodulatory drugs (IMiDs). The RRMM cohort also demonstrated better OS, ORR, and ≥VGPR rate. However, the NDMM cohort showed no significant improvements in any efficacy outcomes. Despite an increase in severe (grade ≥3) infections, elotuzumab use did not adversely affect rates of severe cytopenias, severe cardiac disorders, or second primary malignancies.
Conclusion: Our results suggest that elotuzumab-containing regimens represent valuable therapeutic options for PI/IMiD-exposed patients with RRMM. In contrast, elotuzumab's role in frontline settings remains limited.
{"title":"Addition of Elotuzumab to Backbone Treatment Regimens for Multiple Myeloma: An Updated Meta-Analysis of Randomized Clinical Trials.","authors":"Bruno Almeida Costa, Thomaz Alexandre Costa, Gabriel Cavalcante Lima Chagas, Tarek H Mouhieddine, Joshua Richter, Saad Z Usmani, Sham Mailankody, Sridevi Rajeeve, Hamza Hashmi","doi":"10.1016/j.clml.2024.09.008","DOIUrl":"https://doi.org/10.1016/j.clml.2024.09.008","url":null,"abstract":"<p><strong>Background: </strong>The efficacy of elotuzumab, an anti-SLAMF7 monoclonal antibody, in treating relapsed/refractory multiple myeloma (RRMM) and newly-diagnosed multiple myeloma (NDMM) has varied in randomized controlled trials (RCTs). Moreover, there is limited data on its real-world application.</p><p><strong>Patients and methods: </strong>We conducted a systematic review and meta-analysis of RCTs investigating the addition of elotuzumab to backbone antimyeloma regimens. The primary outcome of interest was progression-free survival (PFS). Secondary efficacy outcomes included overall survival (OS), overall response rate (ORR), and rates of very good partial response or better (VGPR). Key toxicities were also evaluated.</p><p><strong>Results: </strong>Three RRMM trials (n = 915) and 5 NDMM trials (n = 1790) were included, with 50% of the 2705 patients receiving elotuzumab-containing triplets or quadruplets. In RRMM settings, elotuzumab use significantly improved PFS (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.60-0.82; P < .001; I² = 0%). This benefit was consistent among patients with high-risk cytogenetics (HR, 0.62; 95% CI, 0.43-0.90; P = .01; I² = 0%) and was particularly evident in those previously treated with proteasome inhibitors (PIs) or immunomodulatory drugs (IMiDs). The RRMM cohort also demonstrated better OS, ORR, and ≥VGPR rate. However, the NDMM cohort showed no significant improvements in any efficacy outcomes. Despite an increase in severe (grade ≥3) infections, elotuzumab use did not adversely affect rates of severe cytopenias, severe cardiac disorders, or second primary malignancies.</p><p><strong>Conclusion: </strong>Our results suggest that elotuzumab-containing regimens represent valuable therapeutic options for PI/IMiD-exposed patients with RRMM. In contrast, elotuzumab's role in frontline settings remains limited.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.1016/j.clml.2024.09.004
Yaping Ju, Sophie Stuart, Yue Zhao, Yi Xie, Luis F Carrillo, Imran Siddiqi, Ling Zhang, Endi Wang
{"title":"CD10-Positive Lymphoplasmacytic Lymphoma: A Diagnostic Pitfall.","authors":"Yaping Ju, Sophie Stuart, Yue Zhao, Yi Xie, Luis F Carrillo, Imran Siddiqi, Ling Zhang, Endi Wang","doi":"10.1016/j.clml.2024.09.004","DOIUrl":"https://doi.org/10.1016/j.clml.2024.09.004","url":null,"abstract":"","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.1016/j.clml.2024.09.003
Andrew Lin, Nicole Pearl, Jessica Flynn, Sean Devlin, Parastoo Dahi, Miguel-Angel Perales, Michael Scordo, Gunjan L Shah
Hematopoietic cell transplantation requires higher doses of chemotherapy, and practices of adjusting the weight because of concerns of organ toxicity are common. This retrospective analysis of 239 adult recipients of autologous hematopoietic cell transplantation for lymphoma assessed the effect of obesity on transplantation outcomes.
Background: Prior data evaluating the impact of obesity in autologous hematopoietic cell transplantation (AHCT) for lymphomas have provided differing results when assessing overall (OS) and progression-free survival (PFS). Impact on survival outcomes have been described, but direct comparison of discrete toxicities is lacking.
Patients and methods: We retrospectively compared outcomes with patients divided between 3 groups: nonobese patients (n = 129), obese patients dosed on adjusted body weight (AdjBW) (n = 32), and obese patients dosed on total body weight (TBW) (n = 78).
Results: In multivariate analysis of OS with the nonobese group as the comparator, outcomes trended worse in obese patients dosed on AdjBW (HR 1.22, 95% CI 0.52-2.85) but were improved in obese patients dosed on TBW (HR 0.19, 95% CI 0.04-0.85, P = .012). PFS of obese patients dosed on AdjBW vs. the nonobese group was comparable (HR 1.19, 95% CI 0.63-2.24), but improved in obese patients dosed on TBW (HR 0.45, 95% CI 0.23-0.89, P = .021). Notably, no differences were noted between groups in gastrointestinal, infectious, renal, or hepatic toxicities.
Conclusion: In summary, our data suggest that recipients of AHCT for lymphoma should be dosed on TBW to maximize curative outcomes with no apparent increase in toxicities.
造血细胞移植需要更高的化疗剂量,因担心器官毒性而调整体重的做法很常见。这项对239名淋巴瘤自体造血细胞移植成年受者的回顾性分析评估了肥胖对移植结果的影响:背景:先前评估肥胖对淋巴瘤自体造血细胞移植(AHCT)影响的数据在评估总生存期(OS)和无进展生存期(PFS)时提供了不同的结果。对生存结果的影响已有描述,但缺乏对离散毒性的直接比较:我们回顾性比较了分为三组的患者的治疗结果:非肥胖患者(n = 129)、按调整体重(AdjBW)用药的肥胖患者(n = 32)和按总重量(TBW)用药的肥胖患者(n = 78):结果:以非肥胖组为对比组进行OS多变量分析,按调整体重(AdjBW)用药的肥胖患者的结果呈恶化趋势(HR 1.22,95% CI 0.52-2.85),但按总体重用药的肥胖患者的结果有所改善(HR 0.19,95% CI 0.04-0.85,P = .012)。使用 AdjBW 的肥胖患者与非肥胖组患者的 PFS 相当(HR 1.19,95% CI 0.63-2.24),但使用 TBW 的肥胖患者的 PFS 有所改善(HR 0.45,95% CI 0.23-0.89,P = .021)。值得注意的是,在胃肠道、感染、肾脏或肝脏毒性方面,组间没有差异:总之,我们的数据表明,淋巴瘤 AHCT 受者的剂量应为 TBW,以便在不明显增加毒性的情况下最大限度地提高治疗效果。
{"title":"Influence of Obesity on the Efficacy and Toxicity of Patients Undergoing Autologous Hematopoietic Cell Transplantation for Lymphoma.","authors":"Andrew Lin, Nicole Pearl, Jessica Flynn, Sean Devlin, Parastoo Dahi, Miguel-Angel Perales, Michael Scordo, Gunjan L Shah","doi":"10.1016/j.clml.2024.09.003","DOIUrl":"https://doi.org/10.1016/j.clml.2024.09.003","url":null,"abstract":"<p><p>Hematopoietic cell transplantation requires higher doses of chemotherapy, and practices of adjusting the weight because of concerns of organ toxicity are common. This retrospective analysis of 239 adult recipients of autologous hematopoietic cell transplantation for lymphoma assessed the effect of obesity on transplantation outcomes.</p><p><strong>Background: </strong>Prior data evaluating the impact of obesity in autologous hematopoietic cell transplantation (AHCT) for lymphomas have provided differing results when assessing overall (OS) and progression-free survival (PFS). Impact on survival outcomes have been described, but direct comparison of discrete toxicities is lacking.</p><p><strong>Patients and methods: </strong>We retrospectively compared outcomes with patients divided between 3 groups: nonobese patients (n = 129), obese patients dosed on adjusted body weight (AdjBW) (n = 32), and obese patients dosed on total body weight (TBW) (n = 78).</p><p><strong>Results: </strong>In multivariate analysis of OS with the nonobese group as the comparator, outcomes trended worse in obese patients dosed on AdjBW (HR 1.22, 95% CI 0.52-2.85) but were improved in obese patients dosed on TBW (HR 0.19, 95% CI 0.04-0.85, P = .012). PFS of obese patients dosed on AdjBW vs. the nonobese group was comparable (HR 1.19, 95% CI 0.63-2.24), but improved in obese patients dosed on TBW (HR 0.45, 95% CI 0.23-0.89, P = .021). Notably, no differences were noted between groups in gastrointestinal, infectious, renal, or hepatic toxicities.</p><p><strong>Conclusion: </strong>In summary, our data suggest that recipients of AHCT for lymphoma should be dosed on TBW to maximize curative outcomes with no apparent increase in toxicities.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.1016/j.clml.2024.09.001
Michael J Hochman, Colin A Vale, Anthony M Hunter
Myelofibrosis (MF) is a chronic myeloid neoplasm characterized by myeloproliferation, bone marrow fibrosis, splenomegaly, and constitutional symptoms related to pro-inflammatory cytokine signaling. Biologically, MF is characterized by constitutive activation of JAK-STAT signaling; accordingly, JAK inhibitors have been rationally developed to treat MF. Following the initial approval of ruxolitinib in 2011, three additional agents have been approved: fedratinib, pacritinib, and momelotinib. As these therapies are noncurative, allogeneic stem cell transplantation remains a key treatment modality and patients with MF who are deemed candidates should be referred to a transplant center. This potentially curative but toxic approach is typically reserved for patients with higher-risk disease, and JAK inhibitors are recommended in the pretransplant setting. JAK inhibitors have proven effective at managing splenomegaly and constitutional symptoms and should be started early in the disease course in patients presenting with these clinical manifestations; asymptomatic patients may initially be followed with close surveillance. Drug-related myelosuppression has been a challenge with initial JAK inhibitors, particularly in patients presenting with a cytopenic phenotype. However, newer agents, namely pacritinib and momelotinib, have proven more effective in this setting and are approved for patients with significant thrombocytopenia and anemia, respectively. Resistance or disease progression is clinically challenging and may be defined by several possible events, such as increasing splenomegaly or progression to accelerated or blast phase disease. However, with multiple JAK inhibitors now approved, sequencing of these agents appears poised to improve outcomes. Additionally, novel JAK inhibitors and JAK inhibitor-based combinations are in clinical development.
骨髓纤维化(MF)是一种慢性骨髓肿瘤,其特征是骨髓增生、骨髓纤维化、脾脏肿大以及与促炎细胞因子信号有关的体征。从生物学角度看,骨髓增生性疾病的特征是 JAK-STAT 信号的构成性激活;因此,人们合理地开发了 JAK 抑制剂来治疗骨髓增生性疾病。继 2011 年首次批准鲁索利替尼之后,又有三种药物获得批准:非瑞替尼、帕克替尼和莫美罗替尼。由于这些疗法都是非根治性的,异基因干细胞移植仍然是一种重要的治疗方式,被认为是候选者的MF患者应被转介到移植中心。这种可能治愈但有毒性的方法通常只用于风险较高的患者,建议在移植前使用JAK抑制剂。事实证明,JAK抑制剂可有效控制脾肿大和体征,对于出现这些临床表现的患者,应在病程早期开始使用;无症状的患者最初可进行密切监测。与药物相关的骨髓抑制一直是最初的 JAK 抑制剂所面临的挑战,尤其是在出现细胞减少表型的患者中。然而,较新的药物,即帕克替尼(pacritinib)和莫美罗替尼(momelotinib),已被证明在这种情况下更为有效,并已获准分别用于有明显血小板减少和贫血的患者。耐药或疾病进展在临床上具有挑战性,可由几种可能发生的情况来定义,如脾脏肿大或进展为加速期或爆发期疾病。不过,随着多种 JAK 抑制剂的获批,对这些药物进行排序似乎有望改善治疗效果。此外,新型 JAK 抑制剂和基于 JAK 抑制剂的联合用药也在临床开发中。
{"title":"SOHO State of the Art Updates and Next Questions | Choosing and Properly Using a JAK Inhibitor in Myelofibrosis.","authors":"Michael J Hochman, Colin A Vale, Anthony M Hunter","doi":"10.1016/j.clml.2024.09.001","DOIUrl":"https://doi.org/10.1016/j.clml.2024.09.001","url":null,"abstract":"<p><p>Myelofibrosis (MF) is a chronic myeloid neoplasm characterized by myeloproliferation, bone marrow fibrosis, splenomegaly, and constitutional symptoms related to pro-inflammatory cytokine signaling. Biologically, MF is characterized by constitutive activation of JAK-STAT signaling; accordingly, JAK inhibitors have been rationally developed to treat MF. Following the initial approval of ruxolitinib in 2011, three additional agents have been approved: fedratinib, pacritinib, and momelotinib. As these therapies are noncurative, allogeneic stem cell transplantation remains a key treatment modality and patients with MF who are deemed candidates should be referred to a transplant center. This potentially curative but toxic approach is typically reserved for patients with higher-risk disease, and JAK inhibitors are recommended in the pretransplant setting. JAK inhibitors have proven effective at managing splenomegaly and constitutional symptoms and should be started early in the disease course in patients presenting with these clinical manifestations; asymptomatic patients may initially be followed with close surveillance. Drug-related myelosuppression has been a challenge with initial JAK inhibitors, particularly in patients presenting with a cytopenic phenotype. However, newer agents, namely pacritinib and momelotinib, have proven more effective in this setting and are approved for patients with significant thrombocytopenia and anemia, respectively. Resistance or disease progression is clinically challenging and may be defined by several possible events, such as increasing splenomegaly or progression to accelerated or blast phase disease. However, with multiple JAK inhibitors now approved, sequencing of these agents appears poised to improve outcomes. Additionally, novel JAK inhibitors and JAK inhibitor-based combinations are in clinical development.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-08DOI: 10.1016/j.clml.2024.09.005
Rachael Straining, Francine Foss, Molly Schiffer, Kejal Amin, Sonal Agarwal, Iris Isufi, Scott Huntington, Shalin Kothari, Stuart Seropian, Michael Girardi, Tarsheen Sethi
Background: T-cell lymphomas are a heterogeneous group of lymphoid malignancies with poor outcomes. Frontline multiagent chemotherapy options include CHOP (prednisone, vincristine, cyclophosphamide, and doxorubicin), brentuximab-CHP, CHOEP, and EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin).
Patients and methods: We report our single institution data for safety and efficacy of EPOCH in 38 patients with aggressive T-cell lymphoma including both peripheral T cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL).
Results: Eighteen patients received EPOCH as first-line and 21 in the relapsed/refractory (R/R) setting. In 36 evaluable patients, the overall response rate (ORR) was 77% (95% CI, 61%-89%) with 19 (53%) patients achieving complete response (CR) (95% CI, 36%-69%). The ORR in first line and R/R settings were 80% (95% CI, 46%-94%) and 75% (95% CI, 52%-90%), respectively. Response rate was similar in African American versus Caucasian patients but was higher in CD30 negative versus positive patients. Most common grade 3/4 adverse events included cytopenias.
Conclusions: Overall, EPOCH was well tolerated with high response rates in first line and R/R setting.
{"title":"Real World Data on Efficacy and Safety of EPOCH in T-Cell Lymphoma.","authors":"Rachael Straining, Francine Foss, Molly Schiffer, Kejal Amin, Sonal Agarwal, Iris Isufi, Scott Huntington, Shalin Kothari, Stuart Seropian, Michael Girardi, Tarsheen Sethi","doi":"10.1016/j.clml.2024.09.005","DOIUrl":"https://doi.org/10.1016/j.clml.2024.09.005","url":null,"abstract":"<p><strong>Background: </strong>T-cell lymphomas are a heterogeneous group of lymphoid malignancies with poor outcomes. Frontline multiagent chemotherapy options include CHOP (prednisone, vincristine, cyclophosphamide, and doxorubicin), brentuximab-CHP, CHOEP, and EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin).</p><p><strong>Patients and methods: </strong>We report our single institution data for safety and efficacy of EPOCH in 38 patients with aggressive T-cell lymphoma including both peripheral T cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL).</p><p><strong>Results: </strong>Eighteen patients received EPOCH as first-line and 21 in the relapsed/refractory (R/R) setting. In 36 evaluable patients, the overall response rate (ORR) was 77% (95% CI, 61%-89%) with 19 (53%) patients achieving complete response (CR) (95% CI, 36%-69%). The ORR in first line and R/R settings were 80% (95% CI, 46%-94%) and 75% (95% CI, 52%-90%), respectively. Response rate was similar in African American versus Caucasian patients but was higher in CD30 negative versus positive patients. Most common grade 3/4 adverse events included cytopenias.</p><p><strong>Conclusions: </strong>Overall, EPOCH was well tolerated with high response rates in first line and R/R setting.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}