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Bortezomib-based therapy improves outcomes, increases toxicity in mantle cell lymphoma
The substitution of bortezomib for vincristine in front-line therapy for mantle cell lymphoma was associated with prolonged PFS and higher response rates, according to phase 3 study results.
However, bortezomib (Velcade, Millennium Pharmaceuticals) also was associated with an increased risk for hematologic toxicity, results showed.
Tadeusz Robak, MD, of the department of hematology at the Medical University of Lodz in Poland, and colleagues evaluated data from 487 patients with newly diagnosed mantle cell lymphoma who were ineligible for stem cell transplantation (median age, 66 years).
Researchers assigned 244 patients to receive six to eight 21-day cycles of the R-CHOP regimen, comprised of rituximab (Rituxan, Genentech/Biogen Idec), cyclophosphamide, doxorubicin, vincristine and prednisone. The other 243 patients received the VR-CAP regimen, which includes the same therapies as R-CHOP aside from the substitution of vincristine with bortezomib.
Median follow-up was 40 months.
Patients assigned VR-CAP demonstrated significantly prolonged median PFS — the study’s primary endpoint — compared with patients assigned R-CHOP by independent radiologic review (24.7 months vs. 14.4 months; HR = 0.63; 95% CI, 0.5-0.79) and investigator assessment (30.7 months vs. 16.1 months; HR = 0.51; 95% CI, 0.41-0.65).
Results showed 53% of patients in the VR-CAP arm responded to treatment compared with 42% in the R-CHOP arm.
Patients assigned bortezomib-based therapy also demonstrated longer median duration of complete response (42.1 months vs. 18 months) and median treatment-free interval (40.6 months vs. 20.5 months).
The rate for 4-year OS was 64% in the VR-CAP arm and 54% in the R-CHOP arm.
A similar proportion of patients in the VR-CAP and R-CHOP arms experienced drug-related adverse events (96% vs. 93%) and discontinued therapy (8% vs. 6%).
However, bortezomib-based therapy was associated with greater rates of neutropenia of any grade (88% vs. 74%), grade 3 or worse neutropenia (85% vs. 67%), thrombocytopenia of any grade (72% vs. 19%), and grade 3 or worse neutropenia (57% vs. 6%).
“A significant prolongation of PFS and improvements in secondary efficacy endpoints were observed with VR-CAP as compared with R-CHOP,” Robak and colleagues concluded. “This improvement was accompanied by additional, predominantly hematologic toxicity.” – by Alexandra Todak
Disclosure: The study was funded by Janssen and Millennium Pharmaceuticals. Robak reports grant support from Celgene, Janssen, Pharmacyclics and Roche. Please see the full study for a list of all other researchers’ relevant financial disclosures.