Efficacy Outcomes Following Treatment with Bruton Tyrosine Kinase Inhibitors (BTKI) for Relapsed/Refractory Mantle Cell Lymphoma (R/R MCL): A Literature-Based Meta-Analysis


Dreyling M1, Shah B2, Wu JJ3, Chen J4, Keeping S4, Chan K4, Wade S5, Peng W3, Kloos I6, Wang M7
1Department of Medicine III, LMU Hospital,, Munich, Germany, 2H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA, 3Kite, a Gilead Company, Santa Monica, CA, USA, 4PRECISIONheor, Vancouver, BC, Canada, 5Wade Outcomes Research and Consulting, Salt Lake City, UT, USA, 6Kite, a Gilead Company, Paris, France, 7MD Anderson Cancer Center, Houston, TX, USA

Objectives: Most MCL patients relapse after first-line therapy, and disease progression after subsequent BTKi therapy (post-BTKi) often leads to poor outcomes. A systematic literature review and meta-analysis were conducted to estimate objective response rates (ORR), progression-free survival (PFS), and overall survival (OS) post-BTKi in patients with R/R MCL.

Methods: Databases (MEDLINE, EMBASE, Cochrane) were searched through January 2020 for studies reporting ORR and/or Kaplan-Meier curves for OS/PFS in patients with R/R MCL treated post-BTKi. The base-case meta-analysis included studies reporting outcomes for various systemic treatments (i.e. mixed treatments) and scenario analysis included additional single-therapy studies evaluating venetoclax, R-BAC, or RiBVD. A generalized linear mixed model was used for pooling ORR. For OS/PFS, alternative parametric survival models were fitted to the Kaplan-Meier curves and parameters of the best-fitting model (i.e. log-normal) were synthesized in a Bayesian framework to estimate between-study heterogeneity and pooled absolute treatment effects. Fixed-effect and random-effects (FE, RE) models were evaluated.

Results: Eight studies (n=7 retrospective observational; n=1 RCT) involving 297 post-BTKi patients (12-73 patients/study) were included in the meta-analysis (pooled characteristics: age 67 years, 77% male, median 2-4 prior therapies, 19% blastoid morphology, 77% Ki-67≥30%, 88% ECOG score 0/1). In the base-case (n=5 studies), the pooled ORR estimate from the RE model was 28% (95% CI: 23%, 34%). In scenario analysis (n=8 studies), the pooled ORR estimate was 43% (95% CI: 27%, 60%), with the RE model preferred due to between-study heterogeneity. Median OS and PFS were 9.5 (95% CI: 5.4, 20.5) months and 6.1 (95% CI: 3.5, 12.8) months, respectively. Across all OS scenarios (different treatments assessed, different start-time of OS measurements), median OS ranged between 8.1-10.7 months.

Conclusions: This meta-analysis of historical salvage therapy demonstrates poor responses and suboptimal survival outcomes with the limited therapeutic options available for post-BTKi R/R MCL.

Conference/Value in Health Info

2022-05, ISPOR 2022, Washington, DC, USA




Study Approaches

Topic Subcategory

Literature Review & Synthesis, Meta-Analysis & Indirect Comparisons


Oncology, Rare and Orphan Diseases

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