Alternating Cytarabine in R-CHOP Induction Therapy Seems Marginal for Elderly Patients

By Patrick Daly - Last Updated: November 21, 2023

Elderly patients with mantle cell lymphoma (MCL) did not exhibit efficacy or safety differences when undergoing induction therapy with R-CHOP versus R-CHOP alternating with rituximab, cytarabine, and dexamethasone (R-HAD), but maintenance therapy with rituximab plus lenalidomide (R2) significantly improved progression-free survival (PFS) versus rituximab alone, based on results from the MCL-R2 elderly trial.

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However, lead author, Vincent Ribrag, MD, of the Gustave Roussy Institute of Cancer in Villejuif, France, and contributors noted that the two maintenance therapies had no difference in overall survival (OS), and the R2 group had increased toxicities.

The study randomized 620 patients between the induction regimens, and subsequently randomized 495 patients between the maintenance regimens. The cohort had a median age of 71 years, was 69% male, and 85% had stage IV, 47% had intermediate-, and 46% had high-risk disease based on MCL International Prognostic Index (MIPI) criteria.

Both regimens were similar at the end of induction therapy. For instance, the overall response rate in the R-CHOP arm was 88% versus 86% in the R-CHOP plus R-HAD, and both arms had a complete response (CR) rate of 33%. Likewise, the R-CHOP and R-CHOP plus R-HAD arms had a PFS rate of 70.6% and 66.8% (P=.28), respectively, and an OS rate of 83% and 83% (P=.92) respectively, by the data cutoff date.

After a median follow-up of 4.2 years of maintenance therapy, the four-year PFS was 60.9% in the R2 arm versus 42.9% in the rituximab monotherapy arm (P=.0002); however, the R2 arm had more recurring adverse events of grade 3 or higher including neutropenia (50.8% vs 19.2%), respiratory tract infection (6.3% vs 0.8%), and skin cancer (5.9% vs 3.2%).

At two years, the OS rates were 87.6% with R2 and 85.1% with rituximab alone. Lastly, researchers noted 46% of patients in the R2 arm required at least one lenalidomide dose reduction.

Overall, the findings suggested that R-CHOP induction therapy alternating with intermediate doses of a cytarabine-containing regimen was comparable with R-CHOP alone in elderly patients with MCL.

Reference

Ribrag V, Safar V, Kluin-Nelemans H, et al. Induction and maintenance therapy in elderly patients with mantle cell lymphoma: double-randomized MCL R2 elderly clinical trial by the European mantle cell lymphoma network. Abstract #979. Presented at the 65th ASH Annual Meeting and Exposition; December 9-12, 2023; San Diego, California.

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