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Expert Point of View: Sergio A. Giralt, MD



We see that transplant and maintenance alone benefits a lot of patients. It is also probably the most cost-effective treatment for myeloma at this time.
— Sergio A. Giralt, MD

Sergio A. Giralt, MD, Chief of the Adult Bone Marrow Transplant Service at Memorial Sloan Kettering Cancer Center, New York, and the Melvin Berlin Family Chair in Multiple Myeloma, commented on the findings of the StaMINA trial for The ASCO Post. He said the results of the largest randomized U.S. trial of transplant in myeloma, at least for the time being, support single autologous transplant followed by lenalidomide (Revlimid) as the standard of care.1

“We see that transplant and maintenance alone benefits a lot of patients. It is also probably the most cost-effective treatment for myeloma at this time,” Dr. Giralt said.

Dr. Giralt, a co-investigator in the study, noted the difficulty of designing trials “that you know will read out 7 years afterward, yet you want the results to still be relevant.” Fortunately, he said, the inclusion of lenalidomide maintenance in all arms was a good bet. “We made an assumption based on [Cancer and Leukemia Group B (CALGB)] 1001042 that turned out to be right—that lenalidomide maintenance would become the standard of care. That’s what happened, and to our surprise, it also turned out to be very good,” he said.

“But the thing the StaMINA investigators did not anticipate was that lenalidomide would provide at least a 4-year remission duration. That makes the bar for the other two arms in the study very high,” he pointed out.

Other Perspectives

Two other myeloma experts pointed out that StaMINA’s results were different from those of a large European trial, EMN02/HO95, which were also presented at the 2016 ASH meeting.3` In that study, 614 patients were randomly assigned to bortezomib (Velcade), melphalan, and prednisone (VMP); single transplant; or tandem transplant. The study found that upfront double transplant after bortezomib-based induction was superior to single transplant in prolonging progression-free survival (median = 45 months vs not reached). The 3-year progression-free survival rates were 60% and 73%, respectively (hazard ratio = 0.66, P = .030), Cavo et al reported.


We can look forward to a few years of follow-up for both trials [StaMINA and EMN02] to determine the best approach and management of the transplant-eligible patient.
— Philip McCarthy, MD

“The BMT CTN 0702 [StaMINA] study results are definitely different from the results of the EMN02 study,” noted Philip McCarthy, MD, Director of the Bone and Marrow Transplant Program and Professor of Oncology and Internal Medicine at Roswell Park Cancer Institute, Buffalo, New York.

“The EMN02 study found that tandem transplant followed by maintenance generates a superior progression-free survival when compared to single transplant followed by maintenance. There are several possible reasons for differences in the two studies. We can look forward to a few years of follow-up for both trials to determine the best approach and management of the transplant-eligible patient,” he said.

Shaji K. Kumar, MD, Professor of Medicine at the Mayo Clinic, Rochester, Minnesota, explored these possible explanations in an interview with The ASCO Post. He expressed concern that about one-third of patients randomized to tandem transplant in StaMINA did not receive the treatment. “We don’t know why, but it certainly could decrease the ability to answer the question,” he suggested.

He also noted that specific induction regimens were not mandated, “so there was no control over what patients received…. One could argue that ­StaMINA picked up the patients once they have successfully completed the induction and likely with good responses and hence includes a very selected group of patients,” he added.


I still believe tandem transplant may have a role in high-risk myeloma, and I would have this discussion with these patients.
— Shaji K. Kumar, MD

“EMN02, on the other hand, started from diagnosis, prescribing the induction and what the patient got for transplant and at each stage. It’s probably a more well-defined population. I think the EMN02 trial clearly showed that two transplants are better than one and that consolidation does add something, but we need more details,” he concluded. “I still believe tandem transplant may have a role in high-risk myeloma, and I would have this discussion with these patients.”

Transplant Underutilized

A risk-adapted approach may help select which patients need more intensive therapy, and this will optimize treatment, Dr. Giralt said. “I don’t think tandem transplant and RVD consolidation will fit every patient. Our goal should be to achieve minimal residual disease in them all, and patients who are not [minimal residual disease]–negative after transplant could be considered for these additional interventions.”

Unfortunately, he said, most patients are not even benefiting from the current standard of care—single transplant and maintenance. In another study presented at this year’s ASH meeting, D’Souza et al examined trends in transplant and found that only 30% of patients are receiving autologous transplant with lenalidomide maintenance.4

“Maintenance is still not standard, and that was very surprising,” Dr. ­Giralt said “StaMINA had very good results—more than 80% survival at 3 years is dramatic—yet we have a severe underutilization of transplant in the United States.” ■

Disclosures: Dr. Kumar has received honoraria from Slyline Diagnostics; consulted for Celgene, Abbvie, Takeda, Amgen, Merck, and Janssen with no personal compensation; and received institutional funding from Takeda, Janssen, Celgene, Sanofi, Novartis, and Merck. Dr. Giralt reported no potential conflicts of interest.

References

1. Stadtmauer EA, et al: LBA-1 Comparison of autologous hematopoietic cell transplant (autoHCT), bortezomib, lenalidomide and dexamethasone consolidation with lenalidomide maintenance, tandem autoHCT with lenalidomide maintenance and autoHCT with lenalidomide maintenance for up-front treatment of patients with multiple myeloma. 2016 ASH Annual Meeting. Abstract LBA-1. Presented December 6, 2016.

2. McCarthy PL, et al: Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med 366:1770-1781, 2012.

3. Cavo M, et al: Upfront single versus double autologous stem cell transplantation for newly diagnosed multiple myeloma. 2016 ASH Annual Meeting. Abstract 991. Presented December 5, 2016.

4. D’Souza A, et al: Tends in pre- and post-transplant therapies prior to first autologous hematopoietic cell transplantation among patients with multiple myeloma in the United States, 2004-2016. 2016 ASH Annual Meeting. Abstract 677. Presented December 5, 2016.


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