Bendamustine/Rituximab Plus Low-Dose Cytarabine Effective in Elderly MCL Patients

Carlo Visco, MD

The combination of rituximab (Rituxan), bendamustine, and low-dose cytarabine (RBAC500) was shown to be an effective induction regimen for elderly patients with mantle cell lymphoma, according to a phase II trial published in The Lancet Haematology.¹

The RBAC500 regimen induced a 91% complete response rate among MCL patients aged ≥65 years. Although the outcomes fell short of the study’s prespecified safety boundary, the regimen was tolerable with manageable hematologic toxicity using dose reduction and supportive care.

“Despite exceeding our prespecified toxicity criteria, this regimen led to high complete response, with a low frequency of severe or life-threatening adverse events. Hematological toxicity was frequent but manageable with dose reduction and supportive care. Responses were durable without the use of maintenance therapy and compared favorably with previously reported regimens, including bendamustine/rituximab, in this patient population,” lead study author Carlo Visco, MD, Department of Cell Therapy and Hematology, San Bortolo Hospital, Vicenza, Italy, and coauthors wrote in their conclusion.

In a previous trial, the R-BAC regimen—comprising rituximab, bendamustine, and intermediate-dose cytarabine (800 mg/m²)—induced a 95% complete response rate in 20 treatment-naive MCL patients aged ≥65 years.² However, their was significant hematologic toxicity, including a 70% rate of grade 3/4 thrombocytopenia. Visco et al sought determine whether combining rituximab and bendamustine with a lower dose of cytarabine at 500 mg/m² would maintain the antitumor activity while decreasing hematologic toxicity in this elderly population.

The researchers enrolled 57 elderly patients (median age, 71 years; range, 67-75) with mantel cell lymphoma between May 2, 2012, and Feb 25, 2014. Seventy-five percent of the patients were male, 63% had bone marrow involvement, and 95% had an ECOG performance status of 0 or 1. Ninety-one percent of patients had stage III-IV disease (Ann Arbor) and 84% of patients had at least intermediate-risk disease based on the Mantle Cell Lymphoma International Prognostic Index.

The RBAC500 regimen consisted of rituximab at 375 mg/m² on day 1, bendamustine at 70 mg/m² on days 2 and 3, and cytarabine at 500 mg/m² on days 2 through 4, every 4 weeks for a maximum of 6 cycles. All treatments were received intravenously. The primary endpoints were complete response rate and toxicity.

Seventy-four percent (n = 42) of patients were disease-free at a median follow-up of 35 months (range, 28-52). The median progression-free survival (PFS; 95% CI, 42 to NR) and median duration of response (95% CI, 54 to NR) were not yet reached. The PFS rate was 76% (95% CI, 65-85). The 2-year overall survival and PFS rates were 86% (95% CI, 74-93) and 81% (95% CI, 68-89), respectively.

Ninety-five percent of patients received 4 or more cycles of RBAC500, with 67% completing 6 cycles. Three patients discontinued due to toxicity. Two patients had disease progression, after the fourth and sixth cycles, respectively.

The most frequent nonhematologic grade 1/2 adverse events (AEs) were fatigue (25%), nausea or vomiting (21%), and infusion-related reactions or tumor lysis syndrome (21%). Thrombocytopenia (52%) and neutropenia (49%) were the most frequent grade 3/4 hematologic toxicities. Dose reductions were required in 72% of patients. There were 12 patient deaths during the study; however, no deaths were related to treatment.

“…RBAC500 is a regimen that is worth studying in a phase III trial. Further studies are needed to confirm our findings,” Visco et al wrote in their conclusion.

References

1. Visco C, Chiappella A, Nassi L, et al. Rituximab, bendamustine, and low-dose cytarabine as induction therapy in elderly patients with mantle cell lymphoma: a multicentre, phase 2 trial from Fondazione Italiana Linfomi. Lancet Haematol. 2017;4(1):e15-e23. doi: 10.1016/S2352-3026(16)30185-5.
2. Visco, C, Finotto, S, Zambello, R et al. Combination of rituximab, bendamustine, and cytarabine for patients with mantle-cell non-Hodgkin lymphoma ineligible for intensive regimens or autologous transplantation. J Clin Oncol. 2013; 31:1442-1449.