T cell lymphoma and secondary primary malignancy risk after commercial CAR T cell therapy

Nature Medicine, Год журнала: 2024, Номер unknown

Опубликована: Янв. 24, 2024

Язык: Английский

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Second primary malignancies after CAR T-cell therapy: A systematic review and meta-analysis of 5,517 lymphoma and myeloma patients

Clinical Cancer Research, Год журнала: 2024, Номер 30(20), С. 4690 - 4700

Опубликована: Сен. 11, 2024

Abstract Purpose: Chimeric antigen receptor (CAR) T-cell therapy is a potent immunotherapy for hematologic malignancies, but patients can develop long-term adverse events, including second primary malignancies (SPM) that impact morbidity and mortality. To delineate the frequency subtypes of SPMs following CAR-T in lymphoma myeloma, we performed systematic review meta-analysis. Experimental Design: A literature search was conducted MEDLINE, Embase, Cochrane CENTRAL databases. Following extraction SPM cases assignment malignant origin, analyzed point estimates using random effects models. Results: We identified 326 across 5,517 from 18 clinical trials 7 real-world studies. With median follow-up 21.7 months, overall estimate 6.0% (95% confidence interval, 4.8%–7.4%). were associated with treatment setting (clinical > studies), duration follow-up, number prior lines, which each confirmed as independent study-level risk factors meta-regression model. subgroup meta-analysis four randomized versus standard-of-care revealed similar either strategy (P = 0.92). In distribution analysis subtypes, most common entity (37%), followed by solid tumors (27%) non-melanoma skin cancers (16%). represented small minority events (1.5%). noted disease- product-specific variations distribution. Conclusions: These data raise awareness clinically relevant event receiving CAR therapy. However, our findings do not indicate higher previous strategies.

Язык: Английский

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Consensus guidelines and recommendations for the management and response assessment of chimeric antigen receptor T-cell therapy in clinical practice for relapsed and refractory multiple myeloma: a report from the International Myeloma Working Group Immunotherapy Committee

The Lancet Oncology, Год журнала: 2024, Номер 25(8), С. e374 - e387

Опубликована: Май 28, 2024

Язык: Английский

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Characterization of second primary malignancies post CAR T-cell therapy: real-world insights from the two global pharmacovigilance databases of FAERS and VigiBase

EClinicalMedicine, Год журнала: 2024, Номер 73, С. 102684 - 102684

Опубликована: Июнь 20, 2024

The FDA's alerts regarding the T-cell lymphoma risk post CAR-T therapy has garnered global attention, yet a comprehensive profile of second primary malignancies (SPMs) following treatment is lacking.

Язык: Английский

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Mechanisms and management of CAR T toxicity

Frontiers in Oncology, Год журнала: 2024, Номер 14

Опубликована: Май 21, 2024

Chimeric antigen receptor (CAR) T cell therapies have dramatically improved treatment outcomes for patients with relapsed or refractory B-cell acute lymphoblastic leukemia, large lymphoma, follicular mantle and multiple myeloma. Despite unprecedented efficacy, CAR can cause a multitude of adverse effects which require monitoring management at specialized centers contribute to morbidity non-relapse mortality. Such toxicities include cytokine release syndrome, immune effector cell-associated neurotoxicity distinct from ICANS, hemophagocytic lymphohistiocytosis-like hematotoxicity that lead prolonged cytopenias infectious complications. This review will discuss the current understanding underlying pathophysiologic mechanisms provide guidelines grading such toxicities.

Язык: Английский

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Comparison of Standard-of-Care Idecabtagene Vicleucel and Ciltacabtagene Autoleucel in Relapsed/Refractory Multiple Myeloma

Journal of Clinical Oncology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 18, 2025

PURPOSE Idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), two B-cell maturation antigen–directed chimeric antigen receptor (CAR) T-cell therapies have demonstrated remarkable efficacy in relapsed/refractory multiple myeloma (RRMM). We compare safety, efficacy, survival among patients with RRMM treated standard-of-care (SOC) ide-cel or cilta-cel. METHODS Data were from a retrospective chart review of leukapheresed by December 31, 2022, the intent to receive SOC cilta-cel at 19 institutions. An inverse probability treatment weighting (IPTW) approach was used outcomes therapy type. RESULTS A total 641 (n = 386) 255). Five hundred eighty-six infused 350 for ide-cel; n 236 cilta-cel) median follow-up 12.6 13.0 months cilta-cel, respectively. After IPTW, patient characteristics well balanced. Cilta-cel associated higher likelihood grade ≥3 cytokine release syndrome (CRS; odds ratio [OR], 6.80 [95% CI, 2.28 20.33]), infections (OR, 2.03 1.41 2.92]), second primary malignancies 1.77 0.89 3.56]), delayed neurotoxicity 20.07 4.46 90.20]). also better responses (≥complete response: OR, 2.42 1.63 3.60]), longer progression-free (hazard [HR], 0.48 0.36 0.63]), overall (HR, 0.67 0.46 0.97]). No associations observed between type immune effector cell–associated syndrome, any CRS, severe cytopenia days 30 90, nonrelapse mortality. consistent findings when repeating analyses restricting cohort during same time period as Food Drug Administration approval (≥March 2022). CONCLUSION superior survival, incidence certain toxicities, compared ide-cel.

Язык: Английский

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The Current Landscape of Secondary Malignancies after CAR T-Cell Therapies: How Could Malignancies Be Prevented?

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(17), С. 9518 - 9518

Опубликована: Сен. 1, 2024

Chimeric antigen receptor (CAR) T-cell therapies have revolutionised the field of haematological malignancies by achieving impressive remission rates in patients with highly refractory malignancies, improving overall survival. To date, six commercial anti-CD19 and anti-BCMA CAR products been approved Food Drug Administration (FDA) for treatment relapsed/refractory B-cell multiple myeloma. The indications are gradually expanding, these being investigated a variety diseases, including non-malignant ones. Despite great success, there several challenges surrounding therapies, such as non-durable responses high-grade toxicities. In addition, new safety concern was added FDA on 28 November 2023 following reports previously treated either or autologous both clinical trials real-world setting. Since then, published presenting incidence analysing risks other secondary after therapies. this opinion article, current landscape is presented, along proposed strategy future research aiming at potentially diminishing abrogating risk developing

Язык: Английский

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Cilta-cel, a BCMA-targeting CAR-T therapy for patients with multiple myeloma

Expert Opinion on Biological Therapy, Год журнала: 2024, Номер 24(5), С. 339 - 350

Опубликована: Май 3, 2024

Introduction Ciltacabtagene autoleucel (cilta-cel), a BCMA-targeting CAR-T therapy, is approved in the United States and Europe for patients with relapsed/refractory multiple myeloma (RRMM) ≥ 1 prior line of therapy (LOT), including proteasome inhibitor an immunomodulatory drug, are lenalidomide refractory.

Язык: Английский

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Novel Treatment Options for Multiple Myeloma

JCO Oncology Practice, Год журнала: 2025, Номер unknown

Опубликована: Янв. 7, 2025

Multiple myeloma (MM), the second most common hematologic malignancy in United States, is characterized by repeated cycles of remission and relapse, with increasing resistance to treatment after each line therapy. Despite virtually incurable nature MM, recent therapeutic breakthroughs have fundamentally reshaped its landscape. This review explores evolving care paradigms, spanning from newly diagnosed MM relapsed or refractory disease. In frontline setting, strategies shifted beyond their traditional emphasis on autologous stem-cell transplant eligibility a broader categorization patients basis suitability for quadruplet relapsed/refractory novel immunotherapies, including chimeric antigen receptor T-cell (CAR-T) therapies bispecific antibodies, revolutionized treatment, offering new hope previously limited options. Precision medicine playing growing role venetoclax showing significant efficacy t(11;14) translocation, advancing targeted therapy this subgroup. On horizon, investigational CAR-T products cereblon E3 ligase modulators, such as mezigdomide iberdomide, may provide faster, more durable responses compared current therapies. addition, belantamab mafodotin, an antibody-drug conjugate withdrawn US market 2022, verge reapproval positive results randomized trials. While these offer potential, challenges remain managing toxicity, ensuring accessibility, optimizing sequencing strategies. As arsenal expands, need personalized plans that balance quality life becomes even essential.

Язык: Английский

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Ciltacabtagene Autoleucel for the Treatment of Relapsed/Refractory Multiple Myeloma: Efficacy, Safety, and Place in Therapy

Cancer Management and Research, Год журнала: 2025, Номер Volume 17, С. 357 - 372

Опубликована: Фев. 1, 2025

Idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) are two chimeric antigen receptor T cell (CAR T) therapies approved for use in patients with relapsed/refractory multiple myeloma (MM). Initially late line MM (>4 prior lines), these were recently 1-2 lines of therapy April 2024. As their outside the pivotal clinical trials continues to expand, it is important critically evaluate safety efficacy therapies. Further, identify that would be most likely benefit from CAR earlier therapy. Cilta-cel was initially studied phase-I LEGEND-2 study, followed by CARTITUDE-1 CARTITUDE-4 trials, demonstrating remarkable efficacy. A recent large real-world study also demonstrated similar efficacy, a mostly trial ineligible patient population. Based on impressive results, cilta-cel currently being newly diagnosed as well smoldering myeloma. Cytokine release syndrome (CRS) immune effector associated neurotoxicity (ICANS) known toxicities (and other Ts), however movement cognitive disorders (delayed neurotoxicity) second primary malignancies an evolving concern. In this article we discuss data existing studies. We propose all who have received ≥4 should considered T. Earlier restricted high-risk disease phenotype (eg, functional disease). This has historically shown poor outcomes standard triplet regimens T: considering availability safe highly effective therapies, potential

Язык: Английский

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