February 2016, Vol. 5, No. 1

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In Newly Diagnosed Myeloma Patients, Triplets Preferred

Brian G.M. Durie, MD

ASH 2015, ASH Highlights

Brian_Durie98pxWhile 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.”

ASH 2015, ASH Highlights - February 12, 2016

Another Study Shows Benefit with a Pediatric Regimen in Young Adults with ALL

A pediatric regimen achieves superior outcomes compared with adult regimens in adolescents and young adults with acute lymphoblastic leukemia (ALL). Several studies have already shown this outcome, and a multicenter phase 2 study presented at the meeting adds further confirmatory evidence in support of this approach. The multicenter phase 2 [ Read More ]

ASH 2015, ASH Highlights - February 12, 2016

Checkpoint Inhibitors in Lymphoma: A New Universe

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 ]