John Theurer Cancer Center Investigators Advance Understanding of Autologous Stem Cell Transplantation (ASCT) in Multiple Myeloma (MM)

Recently published research letter, consensus guidelines, and review article examine role of ASCT as part of continually evolving treatment landscape in MM

Researchers from Hackensack University Medical Center’s John Theurer Cancer Center, a part of Georgetown Lombardi Comprehensive Cancer Center, are advancing understanding of the evolving role of autologous stem cell transplantation (ASCT) in the treatment of multiple myeloma (MM), as reported in three recent publications. The publications, which include a clinical research letter, a consensus guidelines document, and a review article, underscore the continuing importance of ASCT even as the advent of several novel therapies has dramatically transformed the MM treatment landscape.

For the past two decades, high-dose chemotherapy followed by ASCT has been the standard of care for eligible individuals with MM, a disease with an estimated 34,470 newly diagnosed cases in the United States in 2022.1 In recent years the introduction of proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and monoclonal antibodies (MAbs) has improved long-term survival for many patients with standard-risk MM, although the prognosis for patients with high-risk disease has remained poor. Moreover, relapse after ASCT is inevitable with or without lenalidomide maintenance therapy. Nevertheless, ASCT retains a key role in MM treatment.

“The importance of transplant in multiple myeloma cannot be overemphasized. There is not a single study that shows patients who receive autologous stem cell transplant do worse than those who do not,” said Noa Biran, M.D., associate professor of medicine at Hackensack Meridian School of Medicine and a practicing oncologist/hematologist in the Multiple Myeloma Division of John Theurer Cancer Center. “With the treatment landscape changing so quickly, and with increasing use of novel therapies, it is not only important to clarify the role of transplantation itself, but also to identify therapies that may improve outcomes in the post-transplant setting.”

Research letter shows promise of checkpoint inhibition in combination with IMiDs post-ASCT in high-risk patients

“In a high-risk population with a risk of early relapse after transplant, the median progression-free survival was double the expected time,” observed co-author David H. Vesole, M.D., Ph.D., co-director of the Myeloma Division and director of myeloma research at John Theurer Cancer Center. “Moreover, the combination was well-tolerated, with no serious treatment-related adverse events, and the few grade 3 adverse events were manageable. Overall, the results highlight the importance of immune-boosting therapy in the post-transplant setting, while also demonstrating the safety and clinical benefit of checkpoint inhibition – a treatment modality that merits further study in patients with multiple myeloma.”

Consensus guidelines clarify role of transplantation in MM

Dr. Biran participated in an expert panel convened by the American Society for Transplantation and Cellular Therapy (ASTCT) to formulate clinical practice recommendations for the role, timing, and sequencing of ASCT, allogeneic stem cell therapy, and chimeric antigen receptor (CAR) T-cell therapy for patients with newly diagnosed (NDMM) and relapsed/refractory MM (RRMM). The consensus guidelines, published in Transplantation and Cellular Therapy, endorse continued use of ASCT consolidation for patients with NDMM as a standard-of-care option, though the guidelines do not recommend front-line allogeneic transplantation and CAR-T therapy outside the setting of a clinical trial. In the RRMM setting, the panel recommends use of CAR-T therapy in patients with four or more previous lines of therapy and encourages allogeneic stem cell transplantation only in the context of a clinical trial.3

“We hope the guidelines expand the appropriate use of autologous stem cell transplantation for patients with multiple myeloma,” commented Dr. Biran. “Currently, only a small subset of transplant-eligible patients actually undergo transplant, which is a shame. Transplantation can improve survival and quality of life, but not enough patients are taking advantage of it. We also need to counter the perception among some physicians that the availability of novel therapies eliminates the need for transplantation. The reality is we still need it.”

Review supports upfront use of ASCT in MM

Drs. Vesole and Biran are co-authors of an article in The Cancer Journal that reviews the role of front-line ASCT in the management of patients with MM, focusing particularly on NDMM.4 They note that despite the availability of several novel therapies, as well as the induction regimens VAD (vincristine, doxorubicin, dexamethasone), VRD (bortezomib, lenalidomide, dexamethasone), KRD (carfilzomib, lenalidomide, dexamethasone), and various quadruple regimens such as daraVRD (daratumumab plus VRD), ASCT remains superior to continued chemotherapy. Nevertheless, when patients achieve MRD on high-dose chemotherapy, it raises questions about whether to move forward with ASCT.

“If you view all the data across the different induction regimens, the benefit of transplant still holds,” noted Andre Goy, M.D., M.S., chairman and executive director of John Theurer Cancer Center. “Naturally, because of the depth of responses seen with the current biological agents combinations, the question arises of whether we can defer transplantation in patients who achieve MRD negativity post induction, however the answer remains, ‘No, not yet’.”