Clinical Lymphoma, Myeloma & Leukemia最新文献

{"title":"Unusually Indolent CML: Absence of Complete Cytogenetic Response after 10 Years of Tyrosine Kinase Inhibitor Therapy","authors":"Qiudan Shen ,&nbsp;Fadi G. Haddad ,&nbsp;Elias J. Jabbour ,&nbsp;Guilin Tang ,&nbsp;Hong Fang ,&nbsp;Meng Liu ,&nbsp;Aileen Y. Hu ,&nbsp;Wei Wang ,&nbsp;Pei Lin ,&nbsp;Ghayas C. Issa ,&nbsp;Hagop M. Kantarjian ,&nbsp;L. Jeffrey Medeiros ,&nbsp;Shimin Hu","doi":"10.1016/j.clml.2025.04.012","DOIUrl":"10.1016/j.clml.2025.04.012","url":null,"abstract":"<div><h3>Background</h3><div>With BCR::ABL1 tyrosine kinase inhibitor (TKI) therapy, most patients with chronic-phase chronic myeloid leukemia (CML-CP) can achieve complete cytogenetic response (CCyR) within 6 months of therapy. However, no studies have investigated patients who do not achieve CCyR yet maintains stable disease on long-term TKI treatment. Here we investigated 30 CML-CP patients who did not achieve CCyR but remained free of blastic progression for at least 10-year while on TKI therapy.</div></div><div><h3>Materials and Methods</h3><div>Patients diagnosed with CML-CP or accelerated phase who received at least 10 years of TKI treatment, did not achieve CCyR, yet remained free of blastic progression for a minimum of 10 consecutive years during treatment, were included.</div></div><div><h3>Results</h3><div>At TKI initiation, the median blast count in the bone marrow was 2%. During TKI therapy, 16 patients had additional chromosomal abnormalities (ACAs). The most common ACAs were +Ph (<em>n</em> = 9) and +8 (<em>n</em> = 8), mostly transient, while high-risk ACAs were less common (<em>n</em> = 3). <em>BCR::ABL1</em> kinase domain mutations were detected in 20 patients, 12 patients having a single mutation, mostly transient, and 8 having multiple mutations, which were mostly persistent cross TKI therapies. After a median of 4 TKI lines, the best responses included complete hematologic response (CHR) (<em>n</em> = 15), minor cytogenetic response (<em>n</em> = 2), partial cytogenetic response (<em>n</em> = 10), and major molecular response beyond the 10-year period without CCyR (<em>n</em> = 3). Among 15 patients who achieved a response better than CHR, 14 eventually lost their response. After a median follow-up of 245 months from TKI initiation, 6 patients progressed to blast phase after a median of 165 months.</div></div><div><h3>Conclusion</h3><div>Despite not achieving CCyR, most patients in this cohort maintained long-term stable disease. With careful monitoring and individualized TKI treatment, long-term survival may still be achievable in some non-CCyR responders who do not opt for allogenic stem cell transplantation.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"25 8","pages":"Pages e580-e590"},"PeriodicalIF":2.7,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986926","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}

{"title":"SOHO State of the Art Updates and Next Questions | CD7 CAR-T Therapy for Treating CD7-Positive Hematological Malignancies: Clinical Advances and Future Directions.","authors":"Peihua Lu, Jing Long","doi":"10.1016/j.clml.2025.04.011","DOIUrl":"https://doi.org/10.1016/j.clml.2025.04.011","url":null,"abstract":"<p><p>CD7 CAR-T cell therapy has emerged as a promising treatment for relapsed/refractory (R/R) CD7-positive hematological malignancies, offering new hope for patients with limited therapeutic options. This review examines the recent clinical advances, challenges, and future directions of CD7 CAR-T therapy. Clinical trials have demonstrated remarkable efficacy of CD7 chimeric antigen receptor T (CD7 CAR-T) cells in treating T-cell acute lymphoblastic leukemia (T-ALL), T-cell lymphoblastic lymphoma (T-LBL), and other CD7-positive malignancies, with complete remission (CR) rates of 90-95% in bone marrow (BM) and 50% to 60% in extramedullary disease (EMD). Various engineering strategies, including naturally selected CD7-targeted CAR-T cells, gene editing, protein blockers and universal CAR-T cells, have been developed to overcome challenges such as fratricide. While CD7 CAR-T therapy has shown promising initial responses, durable remissions often depend on consolidative allogeneic hematopoietic stem cell transplantation (allo-HSCT). Ongoing research is focused on optimizing CAR designs, improving CAR-T cell persistence, and developing novel combination strategies to enhance long-term outcomes. Safety profiles have been generally manageable, with cytokine release syndrome (CRS) and neurotoxicity being the primary concerns. However, prolonged cytopenias and potential long-term immunodeficiency due to depletion of healthy CD7-positive cells remain areas of active investigation. As CD7 CAR-T therapy continues to evolve, future directions include refining patient selection, exploring dual-targeting approaches, and investigating innovative strategies to integrate CAR-T therapy with allo-HSCT. These advancements aim to improve the efficacy, safety, and accessibility of CD7 CAR-T therapy for patients with CD7-positive hematological malignancies.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076428","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}

{"title":"SOHO State of the Art Updates and Next Questions | Manuscript Title: Bispecific T-Cell Engagers: Sequencing, B-Cell Maturation Antigen, GPRC5D, and Resistance.","authors":"Sabarish Ayyappan, Jeremy Larsen, James Sanchez, Amrita Krishnan","doi":"10.1016/j.clml.2025.04.006","DOIUrl":"https://doi.org/10.1016/j.clml.2025.04.006","url":null,"abstract":"<p><p>Bispecific antibodies (BsAbs) simultaneously engage endogenous T cells and malignant cells via binding to a T-cell epitope and an extracellular tumor antigen, leading to cytotoxic T-cell activity and tumor cell death. The incorporation of BsAbs into the treatment of multiple myeloma (MM) has improved options for patients with advanced relapsed MM. Three BsAbs have been approved by the Food and Drug Administration; 2 target BCMA on the surface of MM cells, while the other targets surface GPRC5D. Many other BsAbs are in development, including those that target antigens other than BCMA and GPRC5D, such as FcRH5, or that feature different binding constructs. As new BsAbs and new anti-MM agents in general become available, the question of sequencing these therapies becomes paramount. Moreover, resistance to therapy leading to disease relapse following initial response remains a major clinical obstacle, driving research into identifying mechanisms of resistance and developing approaches to overcome them. Understanding this topic will also guide how to best sequence therapies. Because BsAbs are dependent on T cell fitness, researchers are studying the concepts of employing combination therapies that improve T cell health, using a fixed duration of treatment to limit T cell exhaustion, and administering BsAbs earlier in the disease course.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093064","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}

{"title":"Real-world Efficacy and Safety of Flumatinib as the First-line Treatment in Patients With de novo Philadelphia-positive Acute Lymphoblastic Leukemia.","authors":"Zhibo Zhang, Jia Yin, Jun Wang, Xuefeng He, Xiaohui Hu, Haiwen Huang, Limin Liu, Miao Miao, Ying Wang, Huiying Qiu, Xiaowen Tang, Depei Wu, Xiao Ma, Weiyang Li","doi":"10.1016/j.clml.2025.04.010","DOIUrl":"https://doi.org/10.1016/j.clml.2025.04.010","url":null,"abstract":"<p><strong>Background: </strong>The real-world data of flumatinib, a China-developed second-generation tyrosine kinase inhibitors (TKI), on Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is limited. This study evaluated the efficacy and safety of flumatinib combined with chemotherapy as first-line therapy for Ph+ ALL.</p><p><strong>Methods: </strong>This multicenter retrospective study included 65 adults with de novo Ph+ ALL treated with flumatinib (600 mg/day) plus intensive chemotherapy. Outcomes included complete remission (CR), CR with minimal residual disease negativity detected by multiparameter flow cytometry (CR _flow-), overall survival (OS), event-free survival (EFS), and adverse events (AEs). Survival and prognostic factors were analyzed using the Kaplan-Meier method.</p><p><strong>Results: </strong>CR and CR _flow- were achieved in 96.9% (63/65) and 58.5% (38/65) of patients postinduction, respectively. At 24 months, OS and EFS were 87.4% and 62.6%, respectively. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) improved EFS (P < .0001) and tended to improve OS (P = .0503). Common hematologic AEs included neutropenia (93.8%) and thrombocytopenia (76.9%); severe nonhematologic AEs were rare. Relapses (17/63) predominantly associated with T315I (10/19) and Y253H (5/19) mutations. Age ≥ 35 years, BCR/ABL1^P210, and ABL1 Y253H mutation were significantly associated with worse OS. Meanwhile, female, ABL1 Y253H mutation, ABL1 T315I mutation, and failure with achievement of MMR after the first course of consolidation therapy were risk factors for EFS.</p><p><strong>Conclusions: </strong>Flumatinib-based regimens demonstrated high efficacy and tolerable toxicity in Ph+ ALL, which was comparable to other second-generation TKIs. T315I and Y253H mutations were key drivers of relapse. Although allo-HSCT enhanced survival, longer follow-up period and prospective trials are warranted to validate these findings.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076427","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}

{"title":"Treatment Patterns, Efficacy, and Tolerability of Belantamab Mafodotin in Patients With Relapsed and/or Refractory Multiple Myeloma: A Real-World Analysis","authors":"Mihir N. Patel ,&nbsp;Susan C. Locke ,&nbsp;Caroline Falvey ,&nbsp;Jesse D. Troy ,&nbsp;Kris W. Herring ,&nbsp;Amanda Bolgioni-Smith ,&nbsp;Cherie Elcock ,&nbsp;Laura Iadeluca ,&nbsp;Cristiana Costa Chase ,&nbsp;Cristina Gasparetto ,&nbsp;Mark S. Newman ,&nbsp;Thomas W. LeBlanc","doi":"10.1016/j.clml.2025.04.008","DOIUrl":"10.1016/j.clml.2025.04.008","url":null,"abstract":"<div><h3>Purpose</h3><div>Belantamab mafodotin is an anti-B cell maturation antigen (BCMA) immunoconjugate for patients with relapsed/refractory multiple myeloma (RRMM). Additional data on its treatment patterns, efficacy, and tolerability in real-world settings are needed.</div></div><div><h3>Patients and Methods</h3><div>This single-site, retrospective study examined 30 adults with multiple myeloma receiving care at Duke Cancer Institute who began belantamab mafodotin monotherapy between 8/5/2020 and 11/22/2022. We described baseline clinical characteristics, disease response (per International Myeloma Working Group [IMWG] criteria, as possible given available bone marrow biopsy data), belantamab mafodotin treatment patterns, and ocular adverse events (per the Keratopathy Visual Acuity [KVA] scale).</div></div><div><h3>Results</h3><div>Across 30 patients, the median number of lines of therapy was 4, 20 patients (87%) were triple-/quad-/penta-refractory, and 7 (23%) had high-risk cytogenetics (per IMWG criteria). Overall response rate was 67%. Progression occurred in 22 patients (73%); median progression-free survival was 9.5 months (95% CI 6.6-15.6). Median overall survival was not reached as of 3-year follow-up. Dose reduction occurred in 19 patients (63%); 65% were due to ocular adverse events, 30% hematologic adverse events. Cycle delay occurred in 28 (93%); 85% were due to ocular adverse events. Keratopathy (any grade) occurred in 28 (93%); 2% of events were grade ≥3. Visual acuity change (any grade) occurred in 27 (90%); 3.3% of events were grade ≥3. Treatment discontinuation from ocular toxicity occurred in 4 (13%).</div></div><div><h3>Conclusion</h3><div>Despite a high incidence of manageable keratopathy, these data demonstrate benefit in belantamab mafodotin in patients with RRMM over an extended time amid dose/cycle modifications.</div></div><div><h3>Registration: ClinicalTrials.gov</h3><div>NCT05986682.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"25 8","pages":"Pages e570-e579.e4"},"PeriodicalIF":2.7,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981233","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}

{"title":"Real-World Evidence Supports Venetoclax as an Additional Option for Patients With t(11;14) Myeloma.","authors":"Jules Higué, Gaetan Basile, Titouan Cazaubiel, Julie Gay, Guillaume Béziat, Martin Gauthier, Miguel Carreiro, Noémie Gadaud, François Lifermann, Reza Tabrizi, Benjamin Hébraud, Miguel Granell, Léopoldine Lapierre, Pierre-Luc Mouchel, Pierre Bories, Jill Corre, Cyrille Hulin, Aurore Perrot","doi":"10.1016/j.clml.2025.04.005","DOIUrl":"https://doi.org/10.1016/j.clml.2025.04.005","url":null,"abstract":"","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976073","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}

{"title":"Stem Cell Mobilization Yields with Daratumumab (Dara) and Lenalidomide (Len)-Containing Quadruplet Induction Therapy in Patients with Newly Diagnosed Multiple Myeloma (NDMM): A Real-World Experience at 2 Institutes","authors":"Cindy Varga ,&nbsp;Myra Robinson ,&nbsp;Vikas Gupta ,&nbsp;Craig C. Hofmeister ,&nbsp;Ajay K. Nooka ,&nbsp;Jonathan L. Kaufman ,&nbsp;Madhav V. Dhodapkar ,&nbsp;Sagar Lonial ,&nbsp;Shanice Borden ,&nbsp;Christopher Ferreri ,&nbsp;Barry Paul ,&nbsp;Shebli Atrash ,&nbsp;Manisha Bhutani ,&nbsp;Peter M. Voorhees ,&nbsp;Nisha S. Joseph","doi":"10.1016/j.clml.2025.04.003","DOIUrl":"10.1016/j.clml.2025.04.003","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Quadruplet therapy has become standard frontline therapy in transplant eligible NDMM patients. Using data from the MASTER and GRIFFIN trials, Chhabra et al. reported that Dara-Len containing quadruplet therapies had minimal impact on stem cell harvesting and engraftment. It is unclear if this remains true in a real-world setting where heterogeneity exists among patients and in institutional practices. Herein, we describe our experience of stem cell mobilization and collection in NDMM patients receiving DRVd at Levine Cancer Institute (LCI) and Emory Winship Cancer Institute.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;In this multi-center retrospective analysis, NDMM patients were eligible if they received DRVd and pursued stem cell collection between September, 2019 and January, 2024 at LCI and January, 2019 and July, 2022 at Emory. Patients either received 10 mcg/kg of growth colony-stimulating factor (G-CSF) daily (LCI) or 7.5 mcg/kg twice daily (Emory) for 4 days prior to collection and 1 dose on the morning of apheresis. Plerixafor was provided on day -1 of apheresis as a preemptive mobilization strategy at LCI and on an as needed basis at Emory. Patients with a suboptimal stem cell yield on day 1 received additional doses of G-CSF with or without rescue plerixafor at both sites followed by a second day of stem cell collection. Stem cell yield failure was defined as the inability to achieve a minimal goal dose of 2.0 × 10&lt;sup&gt;6&lt;/sup&gt; cells/kg. Categorical outcomes were summarized with frequencies and proportions while numerical outcomes were summarized with descriptive statistics. Select data elements were only available in the LCI cohort.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;A total of 423 patients were analyzed. The median patient age was 62 years (range, 23-79), and 38.1% of the cohort was African American. Thirteen percent of the cohort had high risk cytogenetics and 19.1% had ISS stage III disease. At LCI, patients received a median of 4 (range, 1-14) cycles of induction therapy before stem cell collection. In the entire cohort, 88.8% of patients received 21-day cycles and 11.2% received 28-day cycles. Most patients achieved a VGPR or better (87.2%) after induction and, of those with MRD data available at LCI, 41.6% (37 of 89) achieved MRD negative status (at 10&lt;sup&gt;-5&lt;/sup&gt;). Of those with available data (&lt;em&gt;n&lt;/em&gt; = 92), stem cell collection occurred after a median of 4 weeks (range, 2 to 8) from induction completion. All patients at LCI and 308 of the 318 (96.9%) patients at Emory received plerixafor. Among the entire cohort, the median number of total CD34+ cells collected was 9.0 × 10&lt;sup&gt;6&lt;/sup&gt; CD34+ cells/kg (range 0-24.1). By institute, the median number of CD34+ cells across all attempts at LCI was 8.5 × 10&lt;sup&gt;6&lt;/sup&gt; CD34+ cells/kg (range 2.9-18.1) and the median at Emory was 9.0 × 10&lt;sup&gt;6&lt;/sup&gt; CD34+ cells/kg (0-24.1) indicating that there was no significant difference between mobilization strategies","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"25 8","pages":"Pages e563-e569"},"PeriodicalIF":2.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980397","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}

{"title":"Ibrutinib and Venetoclax in Relapsed and Refractory Follicular Lymphoma.","authors":"Chaitra Ujjani, Hongkun Wang, Catherine Broome, Ajay K Gopal, Stephen D Smith, Catherine Lai, Mazyar Shadman, Lori Leslie, Edus H Warren, Ryan Lynch, Nicole Swanson, Trenton Grossfeld, Bruce D Cheson, Kieron Dunleavy","doi":"10.1016/j.clml.2025.04.004","DOIUrl":"https://doi.org/10.1016/j.clml.2025.04.004","url":null,"abstract":"<p><strong>Background: </strong>Bruton tyrosine kinase (BTK) inhibitors are approved in several B-cell malignancies, including the recent authorization of zanubrutinib for relapsed or refractory follicular lymphoma (FL).</p><p><strong>Methods: </strong>Based on preclinical studies demonstrating synergy with ibrutinib and the B-cell lymphoma (BCL)-2 inhibitor, venetoclax, in FL cell lines, we conducted a multicenter phase Ib/II study evaluating this combination in relapsed or refractory FL.</p><p><strong>Results: </strong>The recommended phase 2 dose was ibrutinib 560 mg and venetoclax 600 mg. There was no evidence of clinical tumor lysis syndrome, despite the omission of a venetoclax ramp up. At a median duration of therapy of 6 months, the most common adverse events were low grade diarrhea (83%), infection (75%), and rash (58%). Amongst the 24 patients enrolled, the overall and complete response (CR) rates were 63% and 21%. At a median follow up of 6.9 months, the median progression-free survival was 8.2 months, and the median duration of CR (n = 5) was 38 months.</p><p><strong>Conclusion: </strong>The combination of a BTK and BCL2 inhibitor is efficacious in relapsed/refractory FL and represents a unique dual-targeted approach warranting further investigation.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975316","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}

{"title":"Daratumumab for newly diagnosed multiple myeloma: Pooled analysis of patients aged ≥65 years from GRIFFIN and PERSEUS.","authors":"Paula Rodriguez-Otero, Peter M Voorhees, Mario Boccadoro, Jacob Laubach, Hermann Einsele, Douglas W Sborov, Meletios A Dimopoulos, Annemiek Broijl, Roberto Mina, Andrew Spencer, Fredrik Schjesvold, Rebecca Silbermann, Francesca Gay, Luciano J Costa, Aurore Perrot, Yanfang Liu, Jianping Wang, Anna Sitthi-Amorn, Robin Carson, Annelore Cortoos, Saad Z Usmani, Paul G Richardson, Philippe Moreau, Pieter Sonneveld, Jonathan L Kaufman","doi":"10.1016/j.clml.2025.04.007","DOIUrl":"https://doi.org/10.1016/j.clml.2025.04.007","url":null,"abstract":"<p><strong>Background: </strong>Older adults with newly diagnosed multiple myeloma (NDMM) have poor prognosis and constitute a subgroup of particular interest. In the GRIFFIN (NCT02874742) and PERSEUS (NCT03710603) studies, adding daratumumab to bortezomib/lenalidomide/dexamethasone (VRd) induction/consolidation and lenalidomide (R) maintenance deepened responses and improved progression-free survival (PFS) versus VRd/R in transplant-eligible patients with NDMM. Subgroup analyses of patients aged ≥65 years in PERSEUS demonstrated less pronounced PFS benefits (HRs: 0.97 [computerized algorithm]; 0.87 [independent review committee (IRC)]), potentially due to small event numbers, cytogenetic risk imbalances (high risk: D-VRd, 25.5%; VRd, 19.5%), and specific censoring rules. Here, we report results from a post hoc, pooled analysis of GRIFFIN and PERSEUS in patients aged ≥65 years (D-VRd, n = 122; VRd, n = 115).</p><p><strong>Methods: </strong>Using patient-level data, PFS analysis was evaluated per computerized algorithm in GRIFFIN and IRC in PERSEUS, stratified by International Staging System stage and cytogenetic risk, with no censoring of PFS events after ≥2 missing disease evaluations.</p><p><strong>Results: </strong>At a median follow-up of 49.6/47.5 months (GRIFFIN/PERSEUS), a trend in improved PFS was seen among patients aged ≥65 years favoring D-VRd (HR, 0.56 [95% CI, 0.30-1.01]). D-VRd improved rates of complete response or better (82.8% vs. 67.0%; OR, 2.37 [95% CI, 1.28-4.39]; P = .0046) and minimal residual disease negativity (10^-5; 66.4% vs. 41.7%; OR, 2.75 [95% CI, 1.61-4.71]; P = .0002) versus VRd. No new safety concerns were identified.</p><p><strong>Conclusion: </strong>These data support use of D-VRd followed by D-R maintenance as standard of care for all transplant-eligible patients with NDMM, regardless of age up to 70 years.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983699","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}

{"title":"Feasibility and Safety of Outpatient Model for Administration of Bispecific Antibodies: Proceedings from an International Myeloma Society 21st Annual Meeting Oral Abstract.","authors":"Sara A Scott, Danielle L Roberts, Vikas A Gupta, Nisha S Joseph, Craig C Hofmeister, Madhav V Dhodapkar, Sagar Lonial, Ajay K Nooka, Jonathan L Kaufman","doi":"10.1016/j.clml.2025.04.002","DOIUrl":"https://doi.org/10.1016/j.clml.2025.04.002","url":null,"abstract":"<p><strong>Background: </strong>Teclistamab, elranatamab, and taqluetamab are T-cell redirecting bispecific antibodies (BsAbs) that gained accelerated approval for the treatment of patients with relapsed/refractory multiple myeloma (RRMM). All 3 FDA labels suggest hospitalization for the step-up doses (SUDs) to monitor for CRS and ICANS.</p><p><strong>Methods: </strong>We implemented an institutional protocol to deliver SUD and target doses in the outpatient (OP) setting to minimize hospitalization and reimbursement burdens. Patient disease and social factors were evaluated for OP protocol eligibility. SUDs were administered on days 1, 4 and 8 preceded by acetaminophen, diphenhydramine, and dexamethasone. All patients received prophylactic tocilizumab per institutional protocol. From initiation of SUD #1 until 48-hours after the target dose, patients self-monitored temperature every 8 hours or in the setting of new signs or symptoms suggestive of CRS/ICANS. If fever or neurologic change should occur, patients were educated to take medications (acetaminophen 650 mg, diphenhydramine 50 mg and dexamethasone 20 mg) and present to the Immediate Care Center for assessment and management.</p><p><strong>Results: </strong>From 9/1/2023 to 8/31/2024, 52 patients received OP BsAb SUD. CRS occurred in 10 patients (19.2%, 9/10 events grade 1/2) and ICANS occurred in 3 patients (5.8%, grade 1). Four patients (7.7%) required hospitalization for toxicity management. All patients recovered from CRS and ICANS without additional toxicity.</p><p><strong>Conclusion: </strong>Implementation of this OP BsAb SUD protocol is feasible with acceptable risk of CRS/ICANS and hospitalization without compromising on safety. The low incidence of CRS/ ICANS with prophylactic tocilizumab and premedication and low hospitalization rates make this appealing for selected RRMM patients.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970000","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}