Adding Bortezomib to Lenalidomide, Dex Improves Survival in Previously Untreated Myeloma

ORLANDO ­– The addition of bortezomib to lenalidomide plus dexamethasone for induction therapy in patients with previously untreated multiple myeloma resulted in improvement in progression-free survival and overall survival, a study presented at the 57^th American Society of Hematology (ASH) Annual Meeting & Exposition has shown.¹

Currently, lenalidomide plus dexamethasone is a standard of care for patients with previously untreated multiple myeloma. Researchers sought to compare lenalidomide plus dexamethasone with bortezomib plus lenalidomide and dexamethasone in a phase 3 clinical trial. For the study, researchers enrolled 473 patients and randomly assigned them to receive lenalidomide plus dexamethasone with or without bortezomib as induction therapy.

“This study is a little bit unusual because it includes both patients under and over the age of 65,” lead investigator Brian G.M. Durie, MD, of the International Myeloma Foundation and Cedars-Sinai Comprehensive Cancer Center in Los Angeles, CA, said during his presentation. “We only included patients with free light chains.”

Patients in the lenalidomide and dexamethasone group received lenalidomide 25 mg/day on days 1 to 21 and dexamethasone 40 mg/day on days 1, 8, 15, and 22 of each 28-day cycle for 6 cycles. Patients in the bortezomib arm received lenalidomide 25 mg/day on days 1 to 14, dexamethasone 20 mg/day on days 1, 2, 4, 5, 8, 9, 11, and 12, and bortezomib 1.3 mg/m² IV push on days 1, 4, 8, and 11 of each 21-day cycle for 8 cycles.

All patients also received aspirin 325 mg/day and those who received bortezomib also received herpes simplex virus prophylaxis. Patients then received maintenance therapy until disease progression, unacceptable toxicity, or withdrawal of consent.

Results showed that median progression-free survival was 43 months with bortezomib and 30 months without it (HR, 0.712; 96% CI, 0.56 – 0.906; P = .0018). Median overall survival was 75 months in the bortezomib group and was 64 months in the lenalidomide plus dexamethasone group (HR, 0.709; P = .025). The overall response rate was 81.5% and 71.5%, respectively.

In regard to safety, grade 3 or higher neuropathy was significantly more common in the bortezomib group compared with the lenalidomide and dexamethasone group (P < .0001).

”Both regimens are safe, but with significantly greater grade 3 neuropathic pain and GI adverse events with bortezomib/lenalidomide/dexamethasone (VRd),” Dr. Durie concluded. “VRd induction followed by continuous Rd is a potential new standard of care.”

Reference

1. Durie B, Hoering A, Rajkumar SV, et al. Bortezomib, lenalidomide and dexamethason vs. lenalidomide and dexamethasone in patients (pts) with previously untreated multiple myeloma without an intent for mediate autologous stem cell transplant (ASCT): result of the randomized phase III trial SWOG S0777. Oral presentation at: 57^th American Society of Hematology (ASH) Annual Meeting & Exposition; December 5-8, 2015; Orlando, FL.