In older patients with treatment-naïve mantle cell lymphoma (MCL), the use of rituximab, bendamustine, and low-dose cytarabine (R-BAC) was associated with a high rate of sustained remission, according to the final analysis of a long-term study published in Blood Advances.1 After seven years of follow-up, the median overall survival (OS) and progression-free survival (PFS) were not reached, and the treatment was not associated with any unexpected long-term toxicity.
“These results were obtained without maintenance therapy and compared favorably with any other competitive regimen in the field, including the recent implementation of BTK inhibitors upfront,” said corresponding author Carlo Visco, MD, of the University of Verona in Italy.
R-BAC was studied in the phase II prospective multicenter RBAC500 trial from Fondazione Italiana Linfomi. Between May 2012 and February 2014, 57 patients (median age = 71 years; range = 61-79) with previously untreated, newly diagnosed MCL were enrolled. Of the patients, 44% (n=25) had a high-risk MCL International Prognostic Index (MIPI) score, 31% (n=16) had a Ki67 score of 30% or greater, and 25% (n=14) had blastoid or pleomorphic morphology. Overall, 95% of the patients received at least four cycles of R-BAC, and 67% received six cycles. Earlier results showed that R-BAC was associated with a 91% complete response rate and an 81% two-year PFS.2
The latest results are from a median follow-up of 86 months with 35 surviving patients. The median OS and PFS were not reached. The seven-year OS was 63% (95% CI 49-74), and the seven-year PFS was 55% (95% CI 41-67). Of the 52 patients previously described as responding, the seven-year PFS was 59% (95% CI 44-71) with no relapse or progression reported after the sixth year. Blastoid or pleomorphic morphology was strongly predictive of PFS (hazard ratio = 3.12; p=0.04; 95% CI 1.05-9.28).
DNA samples from the bone marrow or peripheral blood of 31 patients were available for MRD analysis. R-BAC was associated with high MRD negativity at the end of induction, with 81.5% and 85% of the analyzed patients scoring negative in bone marrow and peripheral blood, respectively. Patients who were MRD-negative at the end of treatment had somewhat better outcomes for both PFS and OS than those who were MRD-positive, although this was not statistically significant (seven-year PFS = 65% vs. 40%, p=0.148; seven-year OS = 65% vs. 40%, p=0.162). Of the 22 deaths, 77% were due to lymphoma progression. Six patients developed secondary malignancies, with a cumulative incidence at seven years of 11.2% (95% CI 4.5-21.3) and a median time to secondary malignancy of 68 months.
“There was no signal of late toxicity or an increase in secondary malignancies during the prolonged follow-up,” the authors wrote.
With a median PFS and OS exceeding 50% after seven years, “this regimen has significantly affected the life expectancy of older patients with MCL,” a disease that was associated with a median OS of less than three years a couple of decades ago, the authors concluded.
A limitation of the trial was that no investigation of TP53 function was planned when it was initiated; however, the “FIL VR-BAC trial, which completed recruitment approximately one year ago, will be presented soon,” Dr. Visco said. The trial is evaluating whether the addition of venetoclax after R-BAC improves PFS among patients with high-risk MCL, including disease with TP53 mutations.
“R-BAC confirms to be among the most active chemoimmunotherapy regimens in patients with MCL and can be adopted in clinical practice, provided that judicious dose reductions are implemented in patients older than 75 years or in those experiencing an excess of hematoxicity after the first cycle,” Dr. Visco said.
Any conflicts of interest declared by the authors can be found in the original article.
References
- Tisi MC, Moia R, Patti C, et al. Long-term follow-up of rituximab plus bendamustine and cytarabine in older patients with newly diagnosed MCL. Blood Adv. 2023;7(15):3916-3924.
- 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.
