Dr Visco on the Role of RBAC Dose Reductions for High-Risk MCL

“In [the real-world setting], for most patients, unless the patient is very fit or tolerates the treatment very well, I always suggest avoiding the third day of cytarabine, and to give the [RBAC] cycle in a 2-day fashion.”

Carlo Visco, MD, an associate professor of hematology in the Department of Medicine, coordinator of the Lymphoma Team in the Hematology and Bone Marrow Transplant Unit in the Section of Biomedical Innovation in the Department of Engineering for Innovative Medicine at the University of Verona, discussed the importance of considering dose reductions when administering bendamustine and rituximab plus intermediate-dose cytarabine (RBAC) for patients with high-risk mantle cell lymphoma (MCL).

Visco began by stating that he always suggests dose reductions of the components of the RBAC regimen to his students and colleagues. He contextualized this suggestion by noting that the RBAC regimen itself is one of the most powerful regimens currently available. Furthermore, he emphasized that a major clinical advantage of this therapy is that it is an induction regimen that is not subsequently followed by maintenance rituximab. This allows RBAC therapy to be concluded within a period of 4 to 6 months.

Regarding the specific administration methodology, Visco noted that the original RBAC dosing protocol called for cytarabine to be administered over 3 days, with the third dose of cytarabine falling on the third day of therapy. Although this 3-day schedule was included in the protocol for the phase 2 FIL_V-RBAC study (NCT03567876) of RBAC followed by venetoclax (Venclexta) in patients with MCL, Visco reported that in real-world practice, this approach should be avoided for most patients. Exceptions should only be made if the patient is very fit or tolerates the treatment exceptionally well, he emphasized. Visco stated that he always recommends avoiding the third day of cytarabine, advising instead that the cycle be given in a 2-day fashion. Using the 2-day approach allows hematologists to evaluate the resulting hematotoxicity of the treatment, he added. Based on this evaluation, Visco continued, it might be possible to lower the doses again, specifically suggesting reducing the cytarabine and bendamustine dosing to flat doses of 100 mg/m2 and 500 mg/m2, respectively. Findings from the FIL_V-RBAC study data demonstrated that even with these reduced doses, the regimen remains highly effective, particularly for patients with a low-risk or standard-risk profile, he concluded.