Recent Bendamustine Treatment before Apheresis Has a Negative Impact on Outcomes in Patients with Large B-Cell Lymphoma Receiving Chimeric Antigen Receptor T-Cell Therapy

Iacoboni, Gloria; López, Á.; Jalowiec, Katarzyna Aleksandra; Kwon, Mi; Rejeski, Kai; Garcés, Víctor Navarro; Amat, Paula; Reguera, Juan Luís; Gallur, Laura; Gutiérrez-Herrero, Sara; Roddie, Claire; Oarbeascoa, Gillen; Benzaquén, Ana; Carpio, Cecilia; Corral, Lucía López; Hernani, Rafael; Bastos‐Oreiro, Mariana; Subklewe, Marion; O’Reilly, Maeve; Martín, Lourdes Moreno; Barba, Pere

doi:10.1182/blood-2022-169783

Cited by 21 publications

(18 citation statements)

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“…Bendamustine, a conventional treatment for both aggressive and indolent lymphomas, may attenuate T-cell fitness and has been shown to impair CAR T-cell expansion and thus its efficacy. 21 , 22 Patients in ZUMA-5 with FL who had recent exposure to bendamustine, particularly within 6 months of leukapheresis, had worse efficacy outcomes after axi-cel relative to those with no prior exposure, similar to recent findings with brexucabtagene autoleucel in mantle cell lymphoma. 21 CAR T-cell expansion was less robust, and CCR7 + CD45RA + T cells in axi-cel product were numerically lower with recent bendamustine exposure, which correlates to reduced efficacy with axi-cel in FL.…”

Section: Discussionmentioning

confidence: 52%

Three-year follow-up analysis of axicabtagene ciloleucel in relapsed/refractory indolent non-Hodgkin lymphoma (ZUMA-5)

Neelapu,

Chavez,

Sehgal

et al. 2024

Blood

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Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 CAR T-cell therapy approved for relapsed/refractory (R/R) follicular lymphoma (FL). Approval was supported by the phase 2, multicenter, single-arm ZUMA-5 study of axi-cel in patients with R/R indolent non-Hodgkin lymphoma (iNHL; N=104), including FL and marginal zone lymphoma (MZL). In the primary analysis (17.5 months median follow-up), overall response rate (ORR) was 92% (74% complete response rate). Here we report long-term outcomes from ZUMA-5. Eligible patients with R/R iNHL after ≥2 lines of therapy underwent leukapheresis, followed by lymphodepleting chemotherapy and axi-cel infusion (2×106 CAR T cells/kg). The primary endpoint was ORR, assessed in this analysis by investigators in all enrolled patients (intent-to-treat). After median follow-up of 41.7 months in FL (n=127) and 31.8 months in MZL (n=31), ORR was comparable to the primary analysis (94% in FL; 77% in MZL). Median progression-free survival was 40.2 months in FL and not yet reached in MZL. Medians of overall survival were not reached in either disease type. Grade ≥3 adverse events of interest occurring since the prior analysis were largely in recently treated patients. Clinical and pharmacokinetic outcomes correlated negatively with recent exposure to bendamustine and high metabolic tumor volume. After 3 years of follow-up in ZUMA-5, axi-cel demonstrated continued durable responses, with very few relapses beyond 2 years, and manageable safety in patients with R/R iNHL. The ZUMA-5 study is registered at ClinicalTrials.gov (NCT NCT03105336)

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Section: Discussionmentioning

confidence: 52%

Three-year follow-up analysis of axicabtagene ciloleucel in relapsed/refractory indolent non-Hodgkin lymphoma (ZUMA-5)

Neelapu,

Chavez,

Sehgal

et al. 2024

Blood

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“…Bendamustine may negatively impact on leucocyte apheresis before CAR-T therapy. 31,32 Polatuzumab with rituximab has only emerged as a safe and effective bridging regimen for patients undergoing CAR-T therapy. 33 There are ongoing studies that will analyse the use of polatuzumab in earlier lines of therapy.…”

Section: Polatuzumab Vedotin-piiqmentioning

confidence: 99%

“…Marrow involvement and elevated LDH were associated with shorter PFS in this cohort of patients. Bendamustine may negatively impact on leucocyte apheresis before CAR‐T therapy 31,32 . Polatuzumab with rituximab has only emerged as a safe and effective bridging regimen for patients undergoing CAR‐T therapy 33 …”

Section: Non‐cellular Therapy Agentsmentioning

confidence: 99%

Relapsed or refractory large B‐cell lymphoma after chimeric antigen receptor T‐cell therapy: Current challenges and therapeutic options

et al. 2023

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Summary Chimeric antigen receptor (CAR) T‐cell (CAR‐T) therapy can provide durable remission in patients with relapsed or refractory diffuse large B‐cell lymphoma (DLBCL) after failure of chemoimmunotherapy. However, patients who are refractory or relapsing after CAR‐T therapy have poor outcomes. Multiple mechanisms of CAR‐T therapy failure have been proposed but management of these patients remains a challenge. As CAR‐T therapy moves earlier in the treatment of DLBCL, we urgently need trials focused on patients with relapse after CAR‐T therapy. Recent advances in novel immunotherapies such as bispecific antibodies, antibody–drug conjugates and next‐generation CAR‐T therapies may provide avenues for treatment. Here we review the available data on using these drugs after failure of CAR‐T therapy and provide a framework for the ideal sequencing of these novel agents.

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“…115 Stabilisation of disease may be required prior to T-cell harvest and where possible, bendamustine should be avoided due to its potential impact on T-cell fitness. 116 Bridging therapy (BT) is defined as any lymphoma-directed treatment delivered between T-cell harvest and lymphodepletion and may consist of chemoimmunotherapy such as R-BAC, 117 radiotherapy or other targeted therapies such as non-covalent BTKis (ncBTKis) and venetoclax (alone or in combination), although these are unlicensed targeted agents in the United Kingdom. BT practice varies widely, reflective of heterogeneous patient groups, lack of published data, physician preference and geographical variation in cell turnaround times and access to novel therapies.…”

Section: Chimeric Antigen Receptor (Car) T-cell Therapymentioning

confidence: 99%

“…Abrupt cessation of ibrutinib at this stage should be avoided due to risk of tumour flare 115 . Stabilisation of disease may be required prior to T‐cell harvest and where possible, bendamustine should be avoided due to its potential impact on T‐cell fitness 116 …”

Section: Recommendationsmentioning

confidence: 99%

Diagnosis and management of mantle cell lymphoma: A British Society for Haematology Guideline

Eyre,

Bishton,

McCulloch

et al. 2023

Br J Haematol

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The objective of this guideline is to provide healthcare professionals with clear guidance on the diagnosis and management of patients with mantle cell lymphoma. M ETHODOLOGYThis Guideline was compiled according to the BSH process at https:// b-s-h. org. uk/ media/ 16732/ bsh-guida nce-devel opmen t-proce ss-dec-5-18. pdf and represents best practice in both teaching and district hospitals in the United Kingdom. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) nomenclature was used to evaluate the levels of evidence and to assess the strength of recommendations. The GRADE criteria can be found at http:// www. grade worki nggro up. org. Literature review detailsRecommendations included a systematic review of published English language literature from publication of previous British Society for Haematology (BSH) Management of Mantle Cell lymphoma Guidelines 2018 up to 02/2023. The search was limited to English language publications and conference abstracts. Titles/abstracts obtained were curated and manually reviewed by the writing group who conducted additional searches, using sub-section heading terms. In addition, there are some further pertinent references and a consensus of expert opinion where no published data are available. PubMed, MEDLINE, Embase, Cochrane databases and Web of Science were searched using the preliminary search terms: MCL OR Mantle Cell lymphoma OR aggressive Mantle Cell lymphoma OR indolent Mantle Cell lymphoma. Systematic reviews, meta-analysis including guidelines from other countries, prospective clinical trials,

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Recent Bendamustine Treatment before Apheresis Has a Negative Impact on Outcomes in Patients with Large B-Cell Lymphoma Receiving Chimeric Antigen Receptor T-Cell Therapy

Cited by 21 publications

References 0 publications

Three-year follow-up analysis of axicabtagene ciloleucel in relapsed/refractory indolent non-Hodgkin lymphoma (ZUMA-5)

Three-year follow-up analysis of axicabtagene ciloleucel in relapsed/refractory indolent non-Hodgkin lymphoma (ZUMA-5)

Relapsed or refractory large B‐cell lymphoma after chimeric antigen receptor T‐cell therapy: Current challenges and therapeutic options

Diagnosis and management of mantle cell lymphoma: A British Society for Haematology Guideline

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