SAN DIEGO – For adults with mantle cell lymphoma, adding bortezomib to a modified hyper-CVAD (VcR-CVAD) regimen followed by rituximab maintenance induced durable remissions at rates resembling those seen with more intensive chemotherapy followed by autologous hematopoietic stem cell transplantation, according to long-term results from a multicenter phase II trial.
Two-thirds of patients were alive and 50% remained in remission after a median follow-up period of 7.8 years, said Julie E. Chang, MD, who reported the results ofat the annual meeting of the American Society of Hematology. “VcR-CVAD is a moderate-intensity chemotherapy regimen that is tolerable for many older and less fit adult patients as first-line therapy of mantle cell lymphoma,” she emphasized.
Mantle cell lymphoma lacks a clear standard first-line therapy, noted Dr. Chang of the University of Wisconsin in Madison. “We hypothesized that the addition of bortezomib would improve the complete response rate, and maintenance rituximab would improve the remission duration,” she said.
To test that idea, she and her associates enrolled 30 adults with histologically confirmed mantle cell lymphoma who had received either no treatment or just one cycle of CHOP or CHOP-like chemotherapy.
Patients received six 21-day cycles of VcR-CVAD induction chemotherapy. This regimen consisted of rituximab (375 mg/m2 IV) on day 1; bortezomib (1.3 mg/m2 IV) on days 1 and 4; cyclophosphamide (300 mg/m2 IV every 12 hours) on days 1 through 3; doxorubicin (50 mg/m2 IV given as a continuous infusion) on days 1 and 2; vincristine (1 mg IV) on day 3; and dexamethasone (40 mg orally) on days 1 through 4.
Patients were permitted all supportive care measures, including prophylaxis for tumor lysis syndrome, transfusions, and antibiotics. Those with at least a partial response received rituximab consolidation (375 mg/m2 IV per week for 4 weeks) followed by rituximab maintenance (375 mg/m2 IV every 12 weeks for 5 years).
Median age was 61 years (range, 48-74 years), 80% of patients were male, all had advanced-stage disease, 60% were mantle cell lymphoma international prognostic index (MIPI) medium or high risk, and six had blastic morphology, the researchers noted.
Estimated 6-year rates of progression-free and overall survival were 53% (95% confidence interval, 38%-75%) and 70% (95% CI, 55%-84%), respectively. Neither age nor MIPI score significantly affected the chances of progression-free or overall survival, but there was a trend toward worse survival among MIPI high-risk patients.
The 10 deaths included 5 from progressive disease, 3 from complications after allogeneic transplant, and 2 from unrelated causes. No patients who remained progression free for 5 years subsequently relapsed, nor were there late toxicities related to treatment.
A recent phase III trial () confirmed the benefits of adding bortezomib to standard immunochemotherapy in mantle cell lymphoma, Dr. Chang noted. “VcR-CVAD remains an effective therapy choice for initial treatment of MCL, both in younger and older MCL populations,” she concluded.
Dr. Chang had no relevant disclosures. Senior author Brad S. Kahl, MD, disclosed ties to Celgene, Gilead, Infinity, Juno, Pharmacyclics, and Seattle Genetics.