Rituximab maintenance therapy after autologous hematopoietic stem cell transplantation prolonged EFS, PFS and OS among patients aged younger than 66 years at mantle cell lymphoma diagnosis, according to results from a phase 3 clinical trial.
“These results show the efficacy of a cytarabine-based induction regimen free of anthracycline or alkylating agents in patients with this condition,” Steven Le Gouill, MD, PhD, from the department of hematology at CHU de Nantes in France, and colleagues wrote.
Most patients with mantle cell lymphoma respond to initial therapy; however, residual tumor cells may persist after treatment and lead to relapse. Le Gouill and colleagues hypothesized that maintenance therapy could prolong the duration of complete response and reduce the risk for relapse.
The initial analysis — results from which were presented in part at the ASH Annual Meeting and Exposition — included 299 patients (median age, 57 years) with stage II to stage IV mantle cell lymphoma and an ECOG performance status score of less than 3. Of these, 279 received induction therapy with four courses of rituximab (Rituxan; Genentech, Biogen), dexamethasone, high-dose cytarabine and salt platinum — also known as R-DHAP — every 21 days. Patients who achieved a partial response and tumor mass reduction less than 75% received rescue induction therapy with four courses of rituximab plus CHOP chemotherapy once every 14 days prior to autologous HSCT. A total of 257 patients underwent autologous HSCT.
Researchers randomly assigned 240 patients who achieved response after autologous HSCT to rituximab maintenance therapy (n = 120) or observation (n = 120). The rituximab group received one 375 mg/m2 infusion every 2 months for 3 years.
EFS — defined as disease progression, relapse, death, severe infection or allergy to the study drug — served as the primary endpoint. Secondary endpoints included PFS and OS.
Median follow-up was 54.4 months from inclusion and 50.2 months from the time of randomization.
Median PFS and OS were not reached among low-risk and intermediate-risk patients. Among high-risk patients, median PFS was 47.4 months and OS was 56.2 months (P < .001 compared with the low-risk groups).
Four-year EFS was 79% (95% CI, 70-86) in the rituximab group compared with 61% (95% CI, 51-70) in the observation group (P = .001). Researchers calculated an HR for disease progression, relapse, death, allergy or severe infection of 0.46 (95% CI, 0.28-0.74).
A greater proportion of patients in the rituximab group also achieved 4-year PFS (83% vs. 64%; HR for disease progression, relapse or death = 0.4; 95% CI, 0.23-0.68) and OS (89% vs. 80%; HR for mortality = 0.5; 95% CI, 0.26-0.99).
Neutropenia was the most frequent grade 3 or grade 4 adverse event. Three patients in the rituximab group and one in the observation group died of a second cancer.
Researchers noted no late effects of rituximab have been observed. – by Melinda Stevens
Disclosures: Roche and Amgen funded the study. Le Gouill reports personal fees and nonfinancial support from Roche, grant support and personal fees from Janssen-Cilag and personal fees from Celgene outside the submitted work. Please see the study for a list of all other authors’ relevant financial disclosures.