Frontline BR Plus ASCT and Maintenance Rituximab Demonstrates Activity in Transplant-Eligible MCL

Diego Villa, MD, MPH

Bendamustine plus rituximab (Rituxan; BR) followed by autologous stem cell transplant (ASCT) and maintenance rituximab led to comparable outcomes defined by progression-free survival (PFS) and objective response rate (ORR) compared with R-CHOP/R-DHAP and ASCT as induction therapy in patients with mantle cell lymphoma (MCL), according to data from a retrospective analysis published in Blood Advances.

After a median follow-up of 4.3 years (range, 0.2-7.6) in the BR cohort (n = 97) and 7.1 years (range, 0.1-14.8) in the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)/R-DHAP (rituximab, dexamethasone, cytarabine, cisplatin) cohort (n = 232), the median PFS was not yet reached vs 9.5 months (95% CI, 6.5-12.6), respectively. The 5-year PFS rate was 76% (95% CI, 58%-94%) with BR vs 68% (95% CI, 62%-74%) with R-CHOP/R-DHAP. Additionally, no differences were seen in PFS in unadjusted (HR, 0.87; 95% CI, 0.53-1.41; P = .56) or adjusted (HR, 0.79; 95% CI, 0.45-1.37; P = .40) comparisons.

“This retrospective adjusted comparison of 2 independent cohorts of younger patients with MCL suggests that BR with ASCT and maintenance rituximab is a feasible and effective first-line treatment, with outcomes comparable to R-CHOP/R-DHAP with ASCT,” lead study author Diego Villa, MD, MPH, a clinical associate professor at The University of British Columbia in Vancouver, Canada, and coauthors, wrote in the study.

Standard frontline therapy in young, fit patients with MCL involves the combination of rituximab and cytotoxic chemotherapy, high-dose chemotherapy and ASCT, and maintenance rituximab.

Findings from the phase 3 MCL Younger trial (NCT00209222) showed that alternating R-CHOP/R-DHAP and ASCT is associated with a longer time to treatment failure and overall survival (OS) compared with R-CHOP and ASCT. BR has also shown higher response rates and PFS compared with R-CHOP in transplant-ineligible patients with less toxicity, as well as comparable response rates, ASCT rates, and outcomes with R-CHOP. However, BR has never been compared with R-CHOP/R-DHAP as induction therapy prior to ASCT.

As such, the objective of this study was to explore differences in outcomes between first-line BR and R-CHOP/R-DHAP in transplant-eligible patients with MCL.

A population-based cohort of 97 patients aged 18 to 65 years with stage II to IV MCL, consecutively treated with BR, was retrospectively identified at BC Cancer. Baseline characteristics, response rates, and outcomes were compared with the cohort of 232 patients with MCL randomized to the R-CHOP/R-DHAP arm of the MCL Younger trial.

The primary end point of the study was the hazard ratio (HR) of the PFS comparison between both groups, adjusted for MCL International Prognostic Index (MIPI), Ki67 index, and blastoid/pleomorphic morphology. Secondary end points included response rates, ASCT rates, event-free survival (EFS), OS, and time to next treatment (TTNT).

Regarding baseline characteristics, Ann Arbor stage, lactate dehydrogenase, MIPI, blastoid morphology, and MCL35 assignments were similar between both groups. However, patients treated with BR were older, had slightly worse performance status, had a greater proportion of Ki67 of at least 30%, and showed a trend toward higher MIPI risk.

Additional results showed that the ORR with BR was 90%, including a complete response (CR) rate of 54%; 77% of patients proceeded to ASCT and 78% received maintenance rituximab. The ORR with R-CHOP/R-DHAP was 94%, including a CR rate of 54%; 78% proceeded to ASCT and 2% received maintenance rituximab.

Moreover, the ASCT rates were comparable in the treatment arms, at 77% with BR vs 78% with R-CHOP/R-DHAP (P = .890).

The median EFS was NR with BR and 7.9 months (95% CI, 5.9-10) with R-CHOP/R-DHAP (P = .570). The 5-year EFS rates were 70% (95% CI, 51%-89%) and 65% (95% CI, 59%-71%), respectively.

The median OS was also NR with BR vs 13.8 months (95% CI, 9.5-18.1) with R-CHOP/R-DHAP (P = .443). The 5-year OS rates were 79% (95% CI, 64%-94%) and 77% (95% CI, 72%-82%), respectively.

The median TTNT was NR in both arms (P = .918). The 5-year TTNT rate was 24% (95% CI, 14%-36%) in the BR arm vs 27% (95% CI, 21%-33%) in the R-CHOP/R-DHAP arm.

Notably, there were no clear differences in secondary end points in unadjusted or adjusted analyses:

• EFS: unadjusted: (HR, 0.88; 95% CI, 0.56-1.37; P = .57) adjusted: (HR, 0.75; 95% CI, 0.45-1.25; P = .27)
• OS: unadjusted: (HR, 0.81; 95% CI, 0.46-1.40; P = .44) adjusted: (HR, 0.65; 95% CI, 0.24-1.24; P = .19)
• TTNT: unadjusted: (HR, 1.01; 95% CI, 0.62-1.67; P = .918)

The study authors also noted that BR can be safely given in the outpatient setting with less toxicity than R-CHOP/R-DHAP, although detailed toxicity data were not available for review in the BR cohort.

Reference

Villa D, Hoster E, Hermine O, et al. Bendamustine or high-dose cytarabine-based induction with rituximab in transplant-eligible mantle cell lymphoma. Blood Adv. 2022;6(18):5285-5294. doi:10.1182/bloodadvances.2022007371