R-BAC Can Potentially Bridge Later-line Therapy in R/R Mantle Cell Lymphoma

A high response rate was demonstrated with the rituximab (Rituxan), bendamustine, and cytarabine (R-BAC) regimen as treatment of patients with relapsed or refractory mantle cell lymphoma (MCL) following treatment with a Bruton tyrosine kinase (BTK) inhibitor, hinting that the regimen may be an effective bridge to allogeneic stem cell transplantation (alloSCT) in patients who are transplant eligible, according to data from a retrospective cohort study.

The cohort consisted of 36 patients with MCL who were treated in 23 centers in the United Kingdom and Italy. Patients had a median age of 66 years (range, 43-81) and had received a median of 2 prior lines of therapy (range, 1-6). A total of 31 patients had received prior treatment with the BTK inhibitor ibrutinib (Imbruvica). Ibrutinib reportedly led to an overall response rate (ORR) of 68% in these patients with confirmed and unconfirmed complete responses in 32% of patients. Due to progression of disease or failure to respond, patients stopped treatment on the BTK inhibitor.

The ORR received with R-BAC treatment was 83% with 60% of patients having a confirmed CR or unconfirmed CR. At the time of data cutoff, there were 22 progression events and 22 deaths. Among patients who received R-BAC, the median progression-free survival (PFS) was 10.1 months (95% CI, 6.9-13.3) and the median overall survival (OS) was 12.5 months (95% CI, 11.0-14.0). For the retrospective analysis, the median follow-up was 18 months (range, 6-24).

The study investigators also evaluated the difference in median PFS on previous BTK inhibitor therapy versus R-BAC, which was at 9.2 versus 8.6 months, respectively (P= .66). 

Overall, 39% of patients completed R-BAC without consolidation therapy (n = 14), and 33% completed the regimen and went on to alloSCT or donor lymphocyte infusion. Treatment was stopped early in 22% of patients due to progressive disease and in 6% of patients due to treatment toxicity.

Doses of chemotherapy were reduced in 56% of patients, which was inclusive of 17 of the 24 patients who received at least 4 cycles. Twenty-five percent of patients had the doses of both cytarabine and bendamustine reduced, 28% had reductions of the cytarabine dose only, and 1 patient (3%) had a reduction of the cytarabine dose only. It is the opinion of the authors that in less fit patients, including those ≥70 years, day 3 of cytarabine should be omitted. In select cases, treatment may be reduced to day 1 only, and anecdotally this approach was successful in a 76-year-old where PFS reached 28 months.

Eighteen patients were hospitalized, mostly due to neutropenic fever (n = 17), and another 23 patients required blood transfusions. No treatment-related deaths occurred.

Various facts were interpreted from these data. For one, the ORR observed with R-BAC was notable but the PFS revealed that responses with this regimen were not durable. The toxicities experienced with R-BAC were tolerable in the patient population. McCulloch et al noted, however, that many dose reductions were needed; as long as frequent monitoring is completed, the study authors maintained that the regimen could be very effective, even in older patients.

Overall, the study confirmed the synergistic cytotoxicity of bendamustine and cytarabine in MCL and showed that R-BAC could serve an unmet medical need in the post-BTK inhibitor setting of MCL, where no current effective treatment exists.

Reference:

McCulloch R, Visco C, Eyre T, et al. Efficacy of R-BAC in relapsed, refractory mantle cell lymphoma post BTK inhibitor therapy [published online February 3, 2020].Br J Haematol. doi:10.1111/bjh.16416.