“The data continue to support the use of an autologous stem cell transplant up front in the management of patients with myeloma after induction,” he contended.
Studies establishing the efficacy of transplant were done before the era of novel therapies. “Some people said all these novel therapies make transplant less important, but that really hasn’t been borne out. That debate is sort of falling away because we now have some new studies that have come out demonstrating a continued benefit in survival for patients who are able to and undergo an autologous stem cell transplant as part of their care,” he said.
“It is a standard of care and if you want proof of it, you can just look at the number of transplants we are doing of multiple myeloma in the United States every year,” he said. “It continues to increase and continues to be the No. 1 indication for transplant.”
Maintenance therapy post transplant
The best approach to maintenance therapy after transplant remains controversial, according to Dr. Green. Lenalidomide (Revlimid) is the standard of care in the United States based on three large trials, all of which showed a progression-free survival benefit of the drug, and one of which showed an overall survival benefit.
“That’s been the rationale for keeping patients on it,” he said, while noting that trials have differed with respect to patient populations and duration on the drug. However, patients with high-risk features may be good candidates for alternate agents.
Options for relapsed disease
Clonal evolution has become an area of interest as it pertains to treatment decisions in the relapsed myeloma setting. “Myeloma is a wily foe, it evolves over time: We find a good treatment against it and it evolves and there is progression,” Dr. Green said. For example, patients may be found to have a 17p deletion when they previously didn’t have one, which could tilt the treatment decision to bortezomib.
Hematologists should consider putting their patients with relapse on clinical trials testing salvage regimens, he said. “Only 4% of patients in the United States are enrolled in a clinical trial, and 40% of trials are closed due to low accrual. If you can get a patient on a trial, please do.”
A regimen that was successful previously in a given patient can be used again. And the roughly one dozen other options for relapsed disease now include the newcomers carfilzomib (Kyprolis), pomalidomide (Pomalyst), and panobinostat (Farydak).
The old drug melphalan (Alkeran) should not be overlooked either. “Melphalan should still be considered a part of salvage regimens for patients. If they have already undergone transplant or are not transplant candidates, at some point, they should receive melphalan, in my opinion,” he said.
Investigational agents
Various investigational agents are being evaluated in trials in myeloma. They include, for example, daratumumab, an anti-CD38 antibody that achieved a 36% response rate in patients with relapsed or relapsed, refractory disease (N Engl J Med. 2015;24;373[13]:1207-19), and elotuzumab, an anti-SLAM F7 antibody that when combined with lenalidomide and dexamethasone improved progression-free survival in patients with relapsed or refractory disease, both overall and among those with high-risk features (N Engl J Med. 2015;373[7]:621-31).
Chimeric antigen receptor (CAR) T cells also have been tested in myeloma (N Engl J Med. 2015;373[11]:1040-7). “I don’t think that this is going to be the home-run approach, but I do think it’s an interesting proof of principle,” Dr. Green said.
Taken together, data suggest that today, cure is within reach for at least a subset of patients with myeloma. For example, more than a third of those undergoing stem cell transplantation who have a complete response are still alive at 12 years, with some having long-term survival (Blood 2011;118:529-34).
“I’m betting that those are the patients who, if we were able to look back in time, we would have seen they had no evidence of minimal residual disease by looking with more of those technologies we now have available for depth of response,” proposed Dr. Green, who disclosed that he had no relevant conflicts of interest.