Community-Based Trial Suggests No Benefit of Adding Thalidomide or Melphalan to Bortezomib-Based First-Line Treatment of Myeloma
In the U.S. community-based phase IIIB UPFRONT trial reported in the Journal of Clinical Oncology, Niesvizky et al found no benefit of adding thalidomide (Thalomid) or melphalan to first-line bortezomib (Velcade)-based treatment in transplant-ineligible myeloma patients.
Study Details
In the trial, 502 patients from 159 U.S. centers were randomly assigned 1:1:1 between June 2007 and March 2010 to 24 weeks (eight 21-day cycles) of induction bortezomib/dexamethasone (n = 168), bortezomib/thalidomide/dexamethasone (n = 167), or bortezomib/melphalan/prednisone (n = 167) followed by 25 weeks (five 35-day cycles) of bortezomib maintenance.
Induction doses were intravenous bortezomib at 1.3 mg/m2 on days 1, 4, 8, and 11, oral dexamethasone at 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 in cycles 1 to 4 and 1, 2, 4, and 5 in cycles 5 to 8, oral thalidomide at 100 mg on days 1 to 21, and oral melphalan at 9 mg/m2 and oral prednisone at 60 mg/m2 on days 1 to 4 every other cycle. Maintenance bortezomib was given at 1.6 mg/m2 intravenously on days 1, 8, 15, and 22. The primary endpoint was progression-free survival.
Efficacy Outcomes
After a median follow-up of 42.7 months, median progression-free survival was 14.7 months with bortezomib/dexamethasone, 15.4 months with bortezomib/thalidomide/dexamethasone, and 17.3 months with bortezomib/melphalan/prednisone (global P = .46). Median overall survival was 49.8, 51.5, and 53.1 months (global P = .79). Overall response rates were 73%, 80%, and 70%.
Adverse Events
Adverse events of grade ≥ 3 occurred in 78% of the bortezomib/dexamethasone group, 87% of the bortezomib/thalidomide/dexamethasone group, and 83% of the bortezomib/melphalan/prednisone group, with grade ≥ 4 events occurring in 19%, 27%, and 22%.
The most common grade ≥3 adverse events in the bortezomib/dexamethasone group were peripheral neuropathy (22%, 27%, and 20%), diarrhea (11%, 5%, and 10%), and fatigue (11%, 12%, and 8%). The most common in the bortezomib/thalidomide/dexamethasone group were peripheral neuropathy and fatigue, and the most common in the bortezomib/melphalan/prednisone group were peripheral neuropathy, neutropenia (19%), thrombocytopenia (15%), and diarrhea.
The investigators concluded: “Although all bortezomib-containing regimens produced good outcomes, [bortezomib/thalidomide/dexamethasone] and [bortezomib/melphalan/prednisone] did not appear to offer an advantage over [bortezomib/dexamethasone] in transplantation-ineligible patients with myeloma treated in US community practice.”
Ruben Niesvizky, MD, of Weill Cornell Medical College, is the corresponding author for the Journal of Clinical Oncology article.
The study was supported by Millennium Pharmaceuticals, a wholly owned subsidiary of Takeda Pharmaceutical. For full disclosures of the study authors, visit jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
