For ASCT in Myeloma, Does One Size Fit All?

Over the last decade, drug development for multiple myeloma has reached an unprecedented pace, and has led to the expansion of regimens that now include novel agents like bortezomib and lenalidomide. This rapid development has improved patient survival rates, and there is anticipation that this trend will only continue.

At the 2014 ASH Annual Meeting, Philippe Moreau, MD, of the University Hospital Hotel-Dieu of Nantes, France, and Paul G. Richardson, MD, of the Dana-Farber Cancer Institute in Boston debated one such controversy: should all transplant-eligible myeloma patients receive autologous stem cell treatment (ASCT)?

Dr. Moreau took the supporting position, and began by tracing the history of ASCT to highlight the overwhelming successes of high-dose melphalan/ASCT– especially when compared with conventional chemotherapy. Combining novel agents with early stem cell treatment has also produced favorable results, Dr. Moreau noted.

“Patients with myeloma who are given front-line stem cell transplantation are having the same mortality probability as the general population,” he argued. “We may be able to begin to think in terms of curing some patients with a combination of novel agents and front-line stem cell transplants.”

While recent successes in the use of novel agents alone (without front-line stem cell transplant) have led some physicians to question whether transplants are necessary at all, Dr. Moreau contended that preliminary randomized data favor the role of early ASCT with novel agents – rather than novel agents alone.

Early ASCT, he concluded, is safe (with a very low risk of mortality), highly feasible (90% feasibility vs. 69% feasibility of delayed transplants), broadly implemented and trusted, and cost-effective (compared to novel agents used alone).

Is ASCT Safe for All Multiple Myeloma Patients?

When Dr. Richardson took the podium, he made a point that he kept returning to throughout his argument: “Does one size fit all?” Myeloma is a highly heterogeneous disease that changes within the individual patient, making “the individualization of treatment with the advent of novel therapies the absolute priority as we go forward,” he said.

Myeloma treatment has progressed considerably, to the point that myeloma could conceivably become a chronic illness – or one that is functionally curable – Dr. Richardson said. In this context, management of adverse events and comorbidities becomes extremely important.

“Does stem cell transplant benefit every patient, and what is its contribution to survival?” he asked, pointing out that the next wave of therapies will include targeting mutations, genetic changes, and classic cell biology.

In that era of advanced cellular therapies, whether universal high-dose melphalan combined with autologous stem cell rescue would benefit all myeloma patients “is something that we simply do not know, particularly in 2014,” Dr. Richardson said.

“Tolerability, quality of life, relapse, and long-term toxicity are key questions and considerations that we have to take into account,” he continued. “At the present time we don’t know whether stem cell transplant is needed in all MRD patients – or if there are there features that can divide who needs what and when. Hence participation in trials is essential.”

A Stepwise Approach to Myeloma Therapy

Following the debate, Joseph R. Mikhael, MD, MEd, of the Mayo Clinic in Scottsdale, Arizona, offered a practical approach to help clinicians choose a therapy in relapsed myeloma. Given the improved therapeutic strategies discussed by Dr. Richardson and Dr. Moreau, patients are living significantly longer with myeloma, and because of that, many patients will require multiple lines of therapy.

Dr. Mikhael advised clinicians to employ a stepwise approach, addressing several factors to decide on optimal treatment for each patient. The five questions clinicians should ask themselves as part of this approach are:

  • Do I need to treat this patient now? Rapidity of relapse is important.
  • Should I retreat with a previous therapy? Consider the depth and duration of response.
  • Have I employed the “Big 5” (thalidomide, bortezomib, lenalidomide, carfilzomib, and pomalidomide)?
  • Have I used “add-on” agents?
  • Have I considered an individualized, risk-stratified approach?

Using this stepwise approach, Dr. Mikhael said, can help clinicians better tailor their treatments for relapsing patients, resulting in improved outcomes.