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Combination treatment with rituximab demonstrates ‘excellent’ results as induction therapy
Induction therapy with rituximab and bendamustine followed by rituximab plus high-dose cytarabine and then an autologous stem cell transplant increased durable remissions among patients with mantle cell lymphoma, according to findings presented at the ASH Annual Meeting and Exposition.
The results were demonstrated in two clinical trials conducted at Dana-Farber Cancer Institute and Washington University in St. Louis and one off-trial experience at Dana-Farber Cancer Institute, Reid W. Merryman, MD, a clinical fellow in medicine in the department of medical oncology at Dana-Farber Cancer Institute, and colleagues report.
“Induction chemoimmunotherapy followed by autologous stem cell transplant is a standard of care for transplant-eligible patients with untreated mantle cell lymphoma. However, there is no consensus on the optimal induction regimen,” the researchers wrote. “The addition of rituximab [Rituxan; Genentech, Biogen] plus high-dose cytarabine to an R-CHOP-like regimen is associated with better outcomes. In addition, two randomized trials have demonstrated superior efficacy and tolerability for rituximab and bendamustine compared to R-CHOP for untreated mantle cell lymphoma. Herein, we report the results of both phase 2 trials as well as the off-trial experience.”
In all, 86 patients were treated with rituximab and bendamustine followed by rituximab plus high-dose cytarabine. The phase 2 trial conducted at Dana-Farber included 23 patients; the off-trial experience at Dana-Farber included 49 patients and the Washington University in St. Louis trial included 14 patients. Median age was 57 years (range, 30 to 72 years). Most patients (n = 73; 85%) had stage 4 disease.
In the Dana-Farber trial, transplant-eligible patients with untreated mantle cell lymphoma, who ranged in age from 18 to 69 years, received 3 cycles of rituximab and bendamustine followed by 3 cycles of rituximab plus high-dose cytarabine. Rituximab was administered at a dose of 375 mg/m2 on day 1 in all cycles; bendamustine 90 mg/m2 was given on days 1 and 2 in the first three cycles and high-dose cytarabine 3 mg/m2 twice per day was given on days 1 and 2 in the next 3 cycles, with dose decreases for age, renal dysfunction or pre-existing neurotoxicity. Patients in the Dana-Farber off-trial cohort were treated with rituximab and bendamustine followed by rituximab plus high-dose cytarabine at Dana-Farber or consulting practices in the community; the researchers selected these patients retrospectively through clinical and pharmacy databases. Transplant-eligible participants in the Washington University in St. Louis trial, who ranged in age from 18 to 65 years, were treated with rituximab and bendamustine during cycles 1, 3 and 5 and rituximab plus high-dose cytarabine during cycles 2, 4 and 6, using the same dosing protocol as the Dana-Farber trial.
Response was measured with CT scans in the Dana-Farber trial and PET and CT scans in the Dana-Farber off-trial and the Washington University in St. Louis trial.
Almost all patients (94%) finished 6 cycles of treatment with rituximab and bendamustine followed by rituximab plus high-dose cytarabine. Patients in the off-trial were more likely to be treated with a lower starting dose of cytarabine (2 mg/m2) compared with patients in the Dana-Farber trial (76% vs. 38%, respectively).
Overall response and complete response rates across all cohorts were 98% and 92%, respectively, with similar response rates in all groups.
Most patients received an autologous stem cell transplant following treatment (n = 73; 85%) and four more transplants were planned at the time of publication, according to the researchers. Autologous stem cell transplants were not completed in 9 patients because of persistent or progressive disease (n = 3), prolonged cytopenias (n = 3), an ASXL1 mutation without cytopenia that was recognized secondarily (n = 1), patient choice (n = 1) and insufficient stem cell collection (n = 1).
Platelet engraftment following autologous stem cell transplant was deferred in more patients treated with alternating cycles of rituximab and bendamustine followed by rituximab plus high-dose cytarabine compared with patients treated sequentially with the same agents at days 30 (platelets <50, 70% vs. 16%; P = .001) and 100 (platelets <100, 60% vs. 21%; P = .017). A starting dose of cytarabine >2 mg/m2 also correlated with a decreased platelet count at 30 days (platelets <50, 41% vs. 8%; P = .004).
One treatment-related death from respiratory failure and respiratory syncytial virus infection occurred 56 days after autologous stem cell transplant.
Rituximab and bendamustine followed by rituximab plus high-dose cytarabine is “an excellent choice” for induction therapy among transplant-eligible patients with untreated mantle cell lymphoma, according to Merryman and colleagues.
In addition, this regimen “... could be further tested in comparative prospective trials,” the researchers wrote. “Sequential, rather than alternating, rituximab and bendamustine followed by rituximab plus high-dose cytarabine cycles and lower-dose cytarabine may reduce the risk of prolonged thrombocytopenia [after] autologous stem cell transplant.” - by Julia Ernst, MS
Reference:
Merryman RW, et al. Abstract 145. Presented at: ASH Annual Meeting and Exposition; Dec. 1-4, 2018; San Diego.
Disclosures: HemOnc Today was unable to confirm relevant financial disclosures for Merryman at the time of publication. Please see the abstract for all other authors’ relevant financial disclosures.