Kenneth Shain, MD, PhD

Vincent Rajkumar, MD

In interviews with The ASCO Post, Kenneth Shain, MD, PhD, Director of the Myeloma Working Group at Moffitt Cancer Center, Tampa, Florida, and Vincent Rajkumar, MD, Professor of Medicine at the Mayo Clinic in Rochester, Minnesota, commented on the findings of the MAIA trial.

“The study shows that another triplet combination is available for transplant-ineligible patients. The results were outstanding,” Dr. Shain said. Since patients were continued on daratumumab (Darzalex)/lenalidomide (Revlimid)/dexamethasone and lenalidomide/dexamethasone, rather than treated with a limited number of cycles, the design mirrors current clinical practice, he added.

Dr. Shain continued: “I agree that daratumumab/lenalidomide/dexamethasone should become a standard of care, because it’s a great option for patients who may have a reason not to be treated with a proteasome inhibitor.

Using a monoclonal antibody upfront may drive responses deeper and control the disease longer. I hope it will become a game-changer for some patients.”

In the POLLUX study of the triplet regimen in the relapsed setting, the addition of daratumumab reduced the risk of disease progression or death by 63%,¹ noted Dr. Shain. Thus, in a population that is probably more drug-sensitive, we may see even bigger differences,” he predicted.

Words of Caution

However, Dr. Rajkumar cautioned that the MAIA study cannot be compared with other studies, especially SWOG S0777 (as mentioned by Dr. Facon). “We cannot compare the progression-free survival or hazard ratio of daratumumab/lenalidomide/dexamethasone with bortezomib (Velcade)/lenalidomide/dexamethasone in SWOG S0777,” said Dr. Rajkumar. “Bortezomib was given for 8 cycles (approximately 8 months), whereas in the current study, daratumumab was given until disease progression (median of about 4 years). That’s comparing apples and oranges.”

Before replacing bortezomib/lenalidomide/dexamethasone, the daratumumab regimen must show a survival benefit of similar magnitude as the bortezomib regimen, Dr. Rajkumar maintained. “Even then, to change the standard of care, bortezomib/lenalidomide/dexamethasone and daratumumab/lenalidomide/dexamethasone need to be compared head to head. That would be a fair comparison…. Furthermore, the daratumumab regimen is more expensive.”

Dr. Shain agreed that these studies cannot be compared, but he focused on the progression-free survival differences. “You see almost a plateau early on. That’s pretty remarkable, but time will tell,” he added.

Both experts agreed that at this time, although more data are awaited, daratumumab/lenalidomide/dexamethasone is probably best suited for patients who cannot tolerate bortezomib-related toxicity. ■

DISCLOSURE: Dr. Shain has served as an advisor/consultant for Celgene, Janssen, Takeda, and Bristol-Myers Squibb as well as received grant funding from AbbVie. Dr. Rajkumar reported no conflicts of interest.

REFERENCE

1. Dimopoulos MA, Oriol A, Nahi H, et al: Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med 375:1319-1331, 2016.