Bortezomib-Based Therapy as Frontline Treatment for Newly Diagnosed MCL

Chicago—Patients with newly diagnosed mantle cell lymphoma (MCL) who received a bortezomib-based combination therapy had a significant increase in progression-free survival compared with a group who received standard frontline therapy, according to a randomized, open-label, multicenter, phase 3 trial.

At a median follow-up of 40 months, the median progression-free survival was 24.7 months for patients who took bortezomib plus rituximab, cyclophosphamide, doxorubicin, and prednisone and 14.4 months for patients who received standard R-CHOP regimen of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (hazard ratio [HR], 0.63; P<.001). There was no significant difference in overall survival.

Franco Cavalli, MD, the study’s lead author, presented the results during an oral abstract session at the ASCO meeting. The trial was funded by Janssen Global Services, LLC, and Millennium: The Takeda Oncology Company.

In 2009, the FDA approved bortezomib to treat relapsed MCL. It is commonly used as second-line therapy. The injectable drug is administered subcutaneously or intravenously and is also approved for use in patients with multiple myeloma.

Dr. Cavalli said MCL is a rare, incurable, aggressive subtype of non-Hodgkin’s lymphoma. Each year, there are 3000 to 4000 new cases of MCL, accounting for approximately 6% of non-Hodgkin’s lymphoma cases.

In this study, patients were recruited from 128 centers in 28 countries between May 26, 2008, and December 5, 2011. Patients were newly diagnosed with MCL; had measurable stage 2 to stage 4 disease; had an Eastern Cooperative Oncology Group score of 0, 1, or 2; and were ineligible or not considered for bone marrow transplantation. They were then randomized to receive 1.4 mg/m² vincristine or 1.3 mg/m² bortezomib. Each patient also received 375 mg/m² rituximab,
750 mg/m² cyclophosphamide, 50 mg/m² doxorubicin, and 100 mg/m² prednisone. Patients received 6 to 8 cycles that each lasted 21 days.

The study included 487 patients. At baseline, the groups were well-balanced. The median age was
approximately 65 years, nearly 75% were male, and 75% had stage 4 disease.

The median overall survival was 56.3 months in the R-CHOP group and had not been reached in the bortezomib group (HR, 0.8; P=.173). At 4 years, the overall survival rate was 53.9% and 64.4%, respectively.

Dr. Cavalli noted that the overall survival data was not mature and only included approximately one-third of the expected events. He added that there was a trend toward prolonged survival with the bortezomib-based therapy.

A complete response was found in 53% of patients in the bortezomib group and 42% of patients in the R-CHOP group (P=.007). The overall response rate, which included partial responses, was 92% and 90%, respectively (P=.275). The median time to initial response was 1.4 months and 1.6 months, respectively (P<.001).

The median complete response duration was 42.1 months in the bortezomib group and 18 months in the R-CHOP group, while the median treatment-free interval was 40.6 months and 20.5 months, respectively.

Serious adverse events were found in 38% of patients in the bortezomib group and 30% of patients in the R-CHOP group. Furthermore, 9% and 7% of patients, respectively, had an adverse event that led to study discontinuation, while 5% and 6%, respectively, died within 30 days of their last dose.

Dr. Cavalli mentioned that there were more instances of neutropenia and thrombocytopenia in patients who received bortezomib. There was no difference in peripheral neuropathy, although the median time to onset was longer in the bortezomib group.—Tim Casey