Efficacy of sonrotoclax vs pirtobrutinib in post–Bruton tyrosine kinase inhibitor (BTKi) relapsed/refractory (R/R) mantle cell lymphoma (MCL): An indirect comparison.

e19050 Background: Sonrotoclax (BGB-11417-201) and pirtobrutinib (BRUIN MCL trial; NCT03740529) have demonstrated efficacy in separate single-arm post-BTKi R/R MCL studies. In the absence of head-to-head randomized trials, a matching-adjusted indirect comparison (MAIC) was conducted to compare the efficacy of both therapies in a post-BTKi R/R MCL setting. Methods: An unanchored MAIC compared individual patient-level data from the sonrotoclax trial (n=103 [efficacy set]; median OS follow-up, 15.2 months) with aggregate data from the pirtobrutinib trial (n=120 [US Food and Drug Administration efficacy cohort]; median OS follow-up, 9.3 months). Matching covariates were selected based on literature review and clinical expert input. The base-case model maximized covariate adjustment while maintaining an effective sample size (ESS) >50. Sensitivity analyses with adequate sample size (ESS >50) and alternative covariates were conducted to validate the base-case model results. Outcomes included overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Weighted Cox proportional hazards and logistic regression models were used for time-to-event and binary endpoints, respectively. Hazard ratios (HR) and odds ratios (OR) with 95% confidence intervals (95% CI) were reported. Results: In the base-case analysis, sonrotoclax showed a nonsignificant, numerically higher ORR (OR, 1.54; 95% CI, 0.80-2.97), as well as a numerically longer DOR (HR, 0.75; 95% CI, 0.37-1.54), versus pirtobrutinib. Consistent numerical improvements in the sonrotoclax cohort were observed for PFS (HR, 0.73; 95% CI, 0.48-1.11) and OS (HR, 0.66; 95% CI, 0.37-1.15). Sensitivity analyses using alternative covariate sets generated broadly consistent results (Table). Conclusions: Based on the data currently available, the MAIC findings suggest a nonsignificant trend of potential difference in efficacy outcomes between sonrotoclax and pirtobrutinib. Future studies with longer follow-up are warranted. MAIC results comparing efficacy outcomes with sonrotoclax vs pirtobrutinib in post-BTKi R/R MCL. Model ESS n (%) ORR-IRCOR (95% CI) P -value DOR-IRCHR (95% CI) P -value PFS-IRCHR (95% CI) P -value OSHR (95% CI) P -value Base case a-c 55 (53) 1.54(0.80-2.97).20 0.75(0.37-1.54).43 0.73(0.48-1.11).14 0.66(0.37-1.15).14 Sensitivity analysis 1 a,b 97 (94) 1.15(0.67-1.97).62 0.77(0.44-1.36).37 0.90(0.64-1.25).52 0.92(0.59-1.44).71 Sensitivity analysis 2 a 102 (99) 1.14(0.67-1.94).64 0.76(0.43-1.32).32 0.89(0.64-1.23).48 0.92(0.59-1.43).70 Covariates include: a sMIPI, no. of prior therapy lines; b PD to last BTKi; and c blastoid MCL. IRC, independent review committee; PD, progressive disease; sMIPI, simplified Mantle Cell Lymphoma International Prognostic Index.