Matching-Adjusted Indirect Comparison of Brexucabtagene Autoleucel (ZUMA-2) and Pirtobrutinib (BRUIN) in Patients with Relapsed/Refractory Mantle Cell Lymphoma Previously Treated with a Covalent Bruton Tyrosine Kinase Inhibitor.

Brexu-cel Brexucabtagene autoleucel Bruton tyrosine kinase inhibitor CAR T cell therapy KTE-X19 MAIC Mantle cell lymphoma Matching-adjusted indirect comparison Non-Hodgkin lymphoma Pirtobrutinib

Journal

Advances in therapy
ISSN: 1865-8652
Titre abrégé: Adv Ther
Pays: United States
ID NLM: 8611864

Informations de publication

Date de publication:
18 Mar 2024
Historique:
received: 22 12 2023
accepted: 12 02 2024
medline: 18 3 2024
pubmed: 18 3 2024
entrez: 18 3 2024
Statut: aheadofprint

Résumé

Patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) often require multiple lines of treatment and have a poor prognosis, particularly after failing covalent Bruton tyrosine kinase inhibitor (cBTKi) therapy. Newer treatments such as brexucabtagene autoleucel (brexu-cel, chimeric antigen receptor T cell therapy) and pirtobrutinib (non-covalent BTKi) show promise in improving outcomes. Without direct comparative evidence, an unanchored matching-adjusted indirect comparison was conducted to estimate the relative treatment effects of brexu-cel and pirtobrutinib for post-cBTKi R/R MCL. Using logistic propensity score models, individual patient-level data from ZUMA-2 brexu-cel-infused population (N = 68) were weighted to match pre-specified clinically relevant prognostic factors based on study-level data from the BRUIN cBTKi pre-treated cohort (N = 90). The base-case model incorporated the five most pertinent factors reported in ≥ 50% of both trial populations: morphology, MCL International Prognostic Index, number of prior lines of therapy, disease stage, and prior autologous stem cell transplant. A sensitivity analysis additionally incorporated TP53 mutation and Ki-67 proliferation. Relative treatment effects were expressed as odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs). In the base-case model, brexu-cel was associated with higher rates of objective response (OR 10.39 [95% CI 2.81-38.46]) and complete response (OR 10.11 [95% CI 4.26-24.00]), and improved progression-free survival (HR 0.44 [95% CI 0.25-0.75]), compared to pirtobrutinib. Overall survival and duration of response favored brexu-cel over pirtobrutinib but the differences crossed the bounds for statistical significance. Findings were consistent across the adjusted and unadjusted analyses. Findings suggest that brexu-cel may offer clinically and statistically significant benefits regarding objective response, complete response, and progression-free survival compared to pirtobrutinib among patients with R/R MCL after prior cBTKi therapy. Given the short follow-up and high degree of censoring in BRUIN, an analysis incorporating updated BRUIN data may provide more definitive overall survival results.

Identifiants

pubmed: 38494543
doi: 10.1007/s12325-024-02822-z
pii: 10.1007/s12325-024-02822-z
doi:

Types de publication

Journal Article

Langues

eng

Informations de copyright

© 2024. The Author(s).

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Auteurs

Gilles Salles (G)

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Jenny M H Chen (JMH)

PRECISIONheor, Vancouver, BC, Canada. jenny.chen@precisionvh.com.

Ina Zhang (I)

PRECISIONheor, Oakland, CA, USA.

Fabio Kerbauy (F)

Federal University of Sao Paulo and Beneficência Portuguesa de São Paulo, São Paulo, Brazil.

James J Wu (JJ)

Kite, a Gilead Company, Santa Monica, CA, USA.

Sally W Wade (SW)

Wade Outcomes Research and Consulting, Salt Lake City, UT, USA.

Ana Nunes (A)

Kite, a Gilead Company, Santa Monica, CA, USA.

Chaoling Feng (C)

Kite, a Gilead Company, Santa Monica, CA, USA.

Ioana Kloos (I)

Kite, a Gilead Company, Santa Monica, CA, USA.

Weimin Peng (W)

Kite, a Gilead Company, Santa Monica, CA, USA.

Julia T Snider (JT)

Kite, a Gilead Company, Santa Monica, CA, USA.

Dylan Maciel (D)

PRECISIONheor, Vancouver, BC, Canada.

Keith Chan (K)

PRECISIONheor, Vancouver, BC, Canada.

Sam Keeping (S)

PRECISIONheor, Vancouver, BC, Canada.

Bijal Shah (B)

Moffitt Cancer Center, Tampa, FL, USA.

Classifications MeSH