Allogeneic HSCT Retains Role in Relapsed Myeloma

Sergio A. Giralt, MD

Allogeneic hematopoietic stem cell therapy (HSCT) is a reasonable and often curative option for patients with relapsed multiple myeloma, particularly in those who are younger with high-risk disease, said Sergio A. Giralt, MD.

In the relapsed setting, there are now over 10 FDA-approved agents across different classes, leading to much debate over the optimal standard of care. Giralt, a professor of medicine at Weill Cornell Medical College, the Melvin Berlin Family Chair in Multiple Myeloma, and chief attending of Adult Bone Marrow Transplant Service at Memorial Sloan Kettering Cancer Center, said that allogeneic HSCT is the only therapeutic strategy that has demonstrated curative potential in patients who relapse after primary therapy.

Despite the clinical benefit of allogeneic HSCT and the fact that it has been implemented in clinical practice for over 2 decades, Giralt said that the approach still falls under the radar.

“Most patients actually do not undergo allogeneic HSCT, they opt for a sequential strategy of a variety of treatments,” he said. “But eventually, the disease becomes more and more resistant.”

OncLive: What is the current treatment landscape for patients with multiple myeloma?

In an interview with OncLive, Giralt discussed recent data with allogeneic HSCT and why this long-standing modality remains an integral part of treatment for patients with relapsed myeloma.Giralt: The treatment landscape has changed dramatically over the last 2 decades, but it usually follows a simple pattern. Patients who require treatment will get induction therapy, usually with a combination of an immunomodulatory agent, proteasome inhibitor, and steroids. After 4 to 6 cycles, they will have their stem cells collected and undergo 1 or 2 transplants.

In the United States, the most common approach is 1 transplant with high-dose melphalan. Patients are then placed on maintenance therapy. Usually, patients are segregated into those who are high risk, based on International Staging System [criteria] or cytogenetic risk profiling. Patients who are high risk are generally recommended to participate in clinical trials exploring novel maintenance strategies beyond lenalidomide (Revlimid). Patients with standard risk will receive lenalidomide maintenance, and we usually see good results. The average progression-free survival is about 4 years, although 15% to 20% of patients will relapse within the first 2 years. These patients are then considered high-risk.

For salvage therapy, there are a variety of options; but in general, a patient who has relapsed after primary therapy is not considered curable unless they undergo an allogeneic HSCT. Most patients actually do not undergo an allogeneic HSCT, they opt for a sequential strategy of a variety of treatments. But eventually, the disease becomes more and more resistant.

What are the biggest benefits of allogeneic HSCT in myeloma?

Could you expand on the follow-up data that have used HSCT in patients who have relapsed more than once?

In the last year, we have actually heard interesting results of chimeric antigen receptor (CAR) T-cell therapy in myeloma—[it is associated with] very high response rates. Allogeneic HSCT is when patients receive high doses of chemotherapy and radiation, and then they receive stem cells from a human leukocyte antigen (HLA) compatible donor. This procedure has been done now for more than 2 decades, but it's the only procedure that is associated with long-term disease control and curative strategies for relapsed myeloma. There are novel techniques to make allogeneic HSCT better and faster for patients in the future. We consider it a valid strategy for patients—particularly young patients with relapsed disease.Allogeneic HSCT for relapsed multiple myeloma has a long track record. Next, it is associated with chances for long-term disease control or clinical benefit. The results have also improved dramatically over the last few years, and it should be considered a valid therapeutic option for young patients with relapsed disease [that has relapsed multiple times]. It can even be considered as part of upfront treatment for young patients with high-risk disease.There have been a variety of randomized trials looking at allogeneic HSCT in the upfront setting of multiple myeloma. BMT CTN 0102 was one of the largest studies in which patients who had an HLA compatible donor were assigned to undergo allogeneic HSCT as consolidation of an autologous transplant.

What are your take-home messages?

If an HLA identical donor was not available within the family, these patients received a tandem autologous transplant. In this study, patients with standard-risk myeloma did not benefit from an allogeneic HSCT. There were not enough patients with high-risk myeloma to make a determination; however, at this time, with a follow-up of 8 years, there are more patients who did not relapse in the allogeneic arm with high-risk disease than those who received an autologous transplant. The risk of relapse was reduced in patients who received an allogeneic HSCT. This suggests there is a graft-versus-myeloma effect that is more operative in patients with high-risk cytogenetic abnormalities and that this strategy needs to be pursued further.Allogeneic HSCT is a valid option and it should not be automatically dismissed just because it has been available for 20 years. We are the first to recognize that results are not what we want them to be. However, there are a number of innovative clinical trials exploring allogeneic HSCT that will hopefully improve outcomes for these patients. More importantly, for a young patient with multiple-relapsed disease, allogeneic HSCT offers a chance for disease control.