Rituximab, Lenalidomide, and Ibrutinib Regimen Exhibits Safe and Effective Outcomes Among Patients With R/R MCL

Results from a Phase 1b Study

The R21 regimen, consisting of the triplet combination of rituximab, lenalidomide, and ibrutinib, exhibited safe and effective outcomes among patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL), including those with high-risk features, according to findings from a phase 1b study published in Leukemia & Lymphoma.

According to Andrew Ip, MD, Hackensack University Medical Center, Hackensack, New Jersey, and coauthors, there have been numerous studies indicating the value of both rituximab and lenalidomide therapy (R2) and ibrutinib and rituximab therapy (Ib-R) among patients with R/R MCL. “Doublets such as R2 or Ib-R have shown greater activity compared to single-agents, providing the rationale for the triplet combination shown here using rituximab, lenalidomide, and ibrutinib (R2I) in patients with R/R MCL,” they stated. 

This phase 1b study aimed to distinguish the maximum tolerated dose (MTD) and assess the safety and activity of this treatment combination among patients with R/R MCL who experienced unsuccessful outcomes to standard chemotherapy. Secondary outcomes included the incidence of grade ≥3 adverse events, best overall response rate (ORR), duration of response, progression-free survival, and overall survival. 

A total of 25 patients with R/R MCL were administered rituximab with escalating doses of lenalidomide on days 1 to 21, and ibrutinib at 560 mg on days 1 to 28 for 28-day cycles. 

The MTD for lenalidomide was 20 mg. The most common grade ≥3 adverse events observed were skin rashes (32%) and neutropenic fever (24%). The best ORR was 88%, the complete response (CR) rate was 83%, and the median duration of response was 36.92 months. 

Notably, responses were observed in refractory patients or patients with high-risk features, including blastoid variant, tumor protein P53 (TP53) mutation, and Ki-67 > 30%. 

Dr Ip et al concluded, “This phase 1b study showed the R2I regimen was safe and tolerable in patients with R/R MCL. The regimen led to very high ORR and CR rate, even in high-risk patients, suggesting that R2I may help to overcome some of the resistance observed in these patients.”

Source: 

Ip A, Petrillo A, Della Pia A, et al. Phase 1b dose-finding study of rituximab, lenalidomide, and ibrutinib (R2I) in patients with relapsed/refractory mantle cell lymphoma. Leuk & Lymph. Published online September 23, 2023. doi: 10.1080/10428194.2023.2259528