Long-Term Outcomes with Ibrutinib Versus the Prior Regimen: A Pooled Analysis in Relapsed/Refractory (R/R) Mantle Cell Lymphoma (MCL) with up to 7.5 Years of Extended Follow-up

Introduction In MCL, progression-free survival (PFS) generally declines with each successive line of chemoimmunotherapy (CIT). We have previously published that with ibrutinib, a first-in-class oral inhibitor of Bruton's tyrosine kinase and a standard of care treatment (tx) for R/R MCL, median PFS exceeded 2 years (yrs) when used at first relapse (Rule S, et al. Haematologica. 2018;104:e211-e214). Here we present an updated pooled analysis with 15 months (mos) of additional follow-up, and for the first time, a comparison of outcomes with ibrutinib versus the prior regimen. Methods Patients (pts) enrolled in SPARK (MCL2001; NCT01599949), RAY (MCL3001; NCT01646021), and PCYC-1104 (NCT01236391) received ibrutinib 560 mg orally once daily until progressive disease or unacceptable toxicity, and pts benefiting at end of study could enroll in the open-label long-term extension study CAN3001 (NCT01804686). Tumor response (by Cheson B, et al; 2007 criteria) and PFS were investigator assessed. Positron emission tomography scans were not routine but confirmatory for complete responses (CRs). Disease evaluations in CAN3001 were per routine clinical practice and pts could continue tx as long as clinically benefiting. For the regimen prior to ibrutinib, time to next tx (TTNT: date of first dose of prior regimen to date of first dose of ibrutinib) was used as a surrogate for PFS. Progression of disease (POD) on frontline tx was categorized as early (TTNT < 24 mos) or late (TTNT ≥ 24 mos). Medians are reported with 95% confidence intervals (CIs). Results As of April 2019, the median (range) follow-up and exposure for 370 ibrutinib-treated pts (median 2 [range 1-9] prior lines of therapy [LOT]) were 41 (0.2-92.4) mos and 11.1 (0.03-92.4) mos, respectively, and 32/87 (37%) pts in CAN3001 remain on ibrutinib. Tx duration was ≥ 3 yrs in 22.4% of pts. At 5 yrs, PFS and overall survival (OS) rates (95% CI) were 19% (15-24) and 41% (35-47), respectively. Pts with 1 prior LOT and pts achieving CR had the best outcomes (Table). Median PFS and OS in pts with 1 prior LOT were 25.4 (17.5-51.8) and 61.6 (36.0-not estimable [NE]) mos, respectively (Figure A). Median PFS and OS in pts with CR were 67.7 (51.7-NE) mos and NR (NE-NE) mos, respectively. Overall, median PFS on ibrutinib was 12.5 (9.8-16.6) mos, while median TTNT on the prior regimen was 10.9 (9.1-12.6) mos (Figure B). PFS with ibrutinib was longer than TTNT on the prior regimen for 50% of pts and was ≥ 12 mos longer than TTN