February 2016, Vol. 5, No. 1
In Newly Diagnosed Myeloma Patients, Triplets PreferredASH 2015, ASH Highlights
While the cost of treating newly diagnosed patients is greatly increased with the use of 3 drugs, doublets should not be considered adequate, and triplets should be the standard of care, according to results from a randomized trial.
The use of triplets—including a proteasome inhibitor, immunomodulatory drug (IMiD), and steroid—has been growing in the United States, and lenalidomide was approved in 2015 for use up front. No randomized trial, however, had proved triplets superior to lenalidomide/dexamethasone alone.
This has now been accomplished in the phase 3 SWOG S0777 trial. Brian G.M. Durie, MD, of the International Myeloma Foundation and Cedars-Sinai Comprehensive Cancer Center, Los Angeles, CA, presented the comparison of bortezomib/lenalidomide/low-dose dexamethasone (VRd) with lenalidomide/dexamethasone (Rd) alone. Both arms received maintenance Rd until progression or unacceptable toxicity.
VRd significantly improved response rates, progression-free survival, and overall survival, Durie reported.
“VRd induction followed by continuous Rd is a potential new standard of care,” he maintained. Sagar Lonial, MD, Professor, Hematology and Medical Oncology, Emory University’s Winship Cancer Institute, Atlanta, GA, said the results solidify the use of 3 drugs as the optimal first-line therapy. A triplet containing a proteasome inhibitor, IMiD, and steroid has “come of age” as the standard of care, he said.
All Outcomes Improved with Triplet
SWOG S0777 randomized 525 patients to VRd or Rd, with both arms offered maintenance Rd.
Overall response rates were 81.5% with VRd and 71.5% with Rd, which included complete responses in 15.7% and 8.4%, respectively. Median progression-free survival was 43 months with VRd and 31 months with Rd (hazard ratio [HR], 0.712; 1-sided P = .0018). Median overall survival was 75 months versus 64 months, respectively (HR, 0.709; 2-sided P = .0250).
The regimens were generally well tolerated; adverse events grade ≥3 were significantly more common in the VRd arm, including neurologic events (33% vs 11%), pain (12% vs 4%), sensory toxicity (23% vs 3%), and gastrointestinal side effects (22% vs 8%).
Durie pointed out that bortezomib was administered intravenously twice a week, which was the way the drug was typically given in 2008 when the study began. Subcutaneous or less frequent administration of bortezomib might have ameliorated some of the toxicity, he suggested.
According to Lonial, “We have now established that a 3-drug induction of an IMiD and proteasome inhibitor is the best combination. Three drugs are better than 2, with the exception of frail patients.”
Cancer Stem Cell Research: A New Frontier in the Fight Against Cancer:
An Interview with Stanton L. Gerson, MD, Case Comprehensive Cancer Center, and Zev A. Wainberg, MD, University of California, Los Angeles
Dr. Gerson is Director of the Case Comprehensive Cancer Center and the Shiverick Professor of Hematological Oncology and Founding Director of the Ohio Wright Center for Stem Cell and Regenerative Medicine, now called the National Center for Regenerative Medicine.Dr. Wainberg is Assistant Professor of Medicine at the University of California, [ Read More ]
Immunotherapy is generating great excitement in melanoma and non–small cell lung cancer (NSCLC). FDA approvals of checkpoint inhibitors in these tumor types, as well as encouraging preliminary results in other solid tumors, have paved the way for studying them in hematologic cancers.Philippe Armand, MD, Dana-Farber Cancer Institute, Boston, MA, discussed [ Read More ]