Outcomes of relapsed mantle cell lymphoma patients after discontinuing acalabrutinib

Jain, Preetesh; Kanagal‐Shamanna, Rashmi; Zhang, Shaojun; Ok, Chi Young; Navsaria, Lucy; Nastoupil, Loretta J.; Lee, Hun Ju; Tang, Guilin; Yin, C. Cameron; Badillo, Maria; Nair, Ranjit; Li, Shaoying; Patel, Keyur; Flowers, Christopher R.; Vega, Francisco; Linghua, Wang; Wang, Michael L.

doi:10.1002/ajh.26109

Cited by 7 publications

(3 citation statements)

References 12 publications

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“…Bruton's tyrosine kinase (BTK) inhibitors (BTKi) are efficacious but not curative, [14][15][16][17][18][19] and the prognosis of R/R MCL after BTKi failure is poor. [20][21][22] Brexucabtagene autoleucel (brexu-cel) is the first US Food and Drug Administration (FDA)-approved autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy 23 for R/R MCL. In the pivotal ZUMA-2 study, the objective response rate (ORR) and the complete response (CR) rate were 91% and 68%, respectively.…”

Section: Introductionmentioning

confidence: 99%

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Brexucabtagene Autoleucel for Relapsed or Refractory Mantle Cell Lymphoma in Standard-of-Care Practice: Results From the US Lymphoma CAR T Consortium

Wang

Jain

Locke

et al. 2023

JCO

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PURPOSE Brexucabtagene autoleucel (brexu-cel) is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory mantle cell lymphoma (MCL). This therapy was approved on the basis of the single-arm phase II ZUMA-2 trial, which showed best overall and complete response rates of 91% and 68%, respectively. We report clinical outcomes with brexu-cel in the standard-of-care setting for the approved indication. PATIENTS AND METHODS Patients who underwent leukapheresis between August 1, 2020 and December 31, 2021, at 16 US institutions, with an intent to manufacture commercial brexu-cel for relapsed/refractory MCL, were included. Patient data were collected for analyses of responses, outcomes, and toxicities as per standard guidelines. RESULTS Of 189 patients who underwent leukapheresis, 168 (89%) received brexu-cel infusion. Of leukapheresed patients, 79% would not have met ZUMA-2 eligibility criteria. Best overall and complete response rates were 90% and 82%, respectively. At a median follow-up of 14.3 months after infusion, the estimates for 6- and 12-month progression-free survival (PFS) were 69% (95% CI, 61 to 75) and 59% (95% CI, 51 to 66), respectively. The nonrelapse mortality was 9.1% at 1 year, primarily because of infections. Grade 3 or higher cytokine release syndrome and neurotoxicity occurred in 8% and 32%, respectively. In univariable analysis, high-risk simplified MCL international prognostic index, high Ki-67, TP53 aberration, complex karyotype, and blastoid/pleomorphic variant were associated with shorter PFS after brexu-cel infusion. Patients with recent bendamustine exposure (within 24 months before leukapheresis) had shorter PFS and overall survival after leukapheresis in intention-to-treat univariable analysis. CONCLUSION In the standard-of-care setting, the efficacy and toxicity of brexu-cel were consistent with those reported in the ZUMA-2 trial. Tumor-intrinsic features of MCL, and possibly recent bendamustine exposure, may be associated with inferior efficacy outcomes.

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Section: Introductionmentioning

confidence: 99%

“…Bruton's tyrosine kinase (BTK) inhibitors (BTKi) are efficacious but not curative, 14-19 and the prognosis of R/R MCL after BTKi failure is poor. 20-22…”

Section: Introductionmentioning

confidence: 99%

Brexucabtagene Autoleucel for Relapsed or Refractory Mantle Cell Lymphoma in Standard-of-Care Practice: Results From the US Lymphoma CAR T Consortium

Wang

Jain

Locke

et al. 2023

JCO

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“…43,[51][52][53] However, the optimal second-line therapy for management of R/R MCL after BTK inhibitor therapy has not been established in prospective studies. 48,54,55 Allogeneic HCT is a potentially curative option for eligible patients with R/R disease that is in remission following second-line therapy. 56 However, with the recent approval of CAR T-cell therapy for R/R MCL, in most NCCN Member Institutions allogeneic HCT has been deferred to disease relapse following multiple prior therapies (including disease relapse following CAR Tcell therapy).…”

Section: Mantle Cell Lymphomamentioning

confidence: 99%

NCCN Guidelines® Insights: B-Cell Lymphomas, Version 5.2021

Zelenetz

Gordon

Chang

et al. 2021

Journal of the National Comprehensive Cancer Network

106

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In the last decade, a better understanding of the molecular pathogenesis of B-cell non-Hodgkin lymphomas has resulted in the development of novel targeted therapies, such as small molecule inhibitors of select kinases in the B-cell receptor pathway, antibody–drug conjugates, and small molecules that target a variety of proteins (eg, CD-19, EZH2, and XPO-1–mediated nuclear export). Anti-CD19 CAR T-cell therapy, first approved for relapsed/refractory (R/R) diffuse large B-cell lymphoma, has also emerged as a novel treatment option for R/R follicular lymphoma and mantle cell lymphoma. These NCCN Guideline Insights highlight the new targeted therapy options included in the NCCN Guidelines for B-Cell Lymphomas for the treatment of R/R disease.

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Sequencing of Novel Therapies for Mantle Cell Lymphoma

Romancik

Cohen

2021

Curr. Treat. Options in Oncol.

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Outcomes of relapsed mantle cell lymphoma patients after discontinuing acalabrutinib

Abstract: Combination therapy with the selective Bcl-2 inhibitor venetoclax and a hypomethylating agent (VEN-HMA) represents a significant step forward in the therapy of acute myeloid leukemia (AML), with high efficacy across multiple biological subtypes of AML, both in E140 CORRESPONDENCE

Cited by 7 publications

References 12 publications

Brexucabtagene Autoleucel for Relapsed or Refractory Mantle Cell Lymphoma in Standard-of-Care Practice: Results From the US Lymphoma CAR T Consortium

Brexucabtagene Autoleucel for Relapsed or Refractory Mantle Cell Lymphoma in Standard-of-Care Practice: Results From the US Lymphoma CAR T Consortium

NCCN Guidelines® Insights: B-Cell Lymphomas, Version 5.2021

Sequencing of Novel Therapies for Mantle Cell Lymphoma

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