Transplant at Relapse: Is It Valuable?
More than two dozen experts from around the world gathered in Minneapolis, Minn. Oct. 27, 2014, to assess the current landscape for autologous stem cell transplant (ASCT) as an option for myeloma patients who have relapsed. “Salvage” transplant—despite its rather gruesome-sounding name—offers an effective treatment choice for patients who have had a positive prior response to transplant.
During this era of novel therapies, salvage transplant has become an overlooked option. Presentations at the recent meeting, held under the auspices of the American Society of Blood and Marrow Transplantation (ASBMT), the Blood and Marrow Transplant Clinical Trials Network> (BMT CTN) Workshop, the National Marrow Donor Program, and the International Myeloma Foundation, suggest that it is time to take a second look at the uses and recommendations for salvage transplant—both the name, perhaps, and the process.
We know that transplant has clear benefits as a high dose consolidation therapy for patients in the frontline setting, as described in the 2011 publication in the journal Blood, International Myeloma Working Group (IMWG) consensus approach to the treatment of multiple myeloma patients who are candidates for autologous stem cell transplantation. The Minnesota workshop provided a wonderful opportunity to re-examine the merits of second transplants as well.
The workshop was co-chaired by Dr. Sergio Giralt (Memorial Sloan Kettering Cancer Center) and Dr. Ed Stadtmauer (University of Pennsylvania School of Medicine, Abramson Cancer Center) representing the Center for International Blood & Marrow Transplant Research (CIBMTR) and the BMT CTN, and myself, representing the IMF and the IMWG. Other organizing committee members were Drs. Hari Parameswaran, Phillip McCarthy, and Marcelo Pasquini.
Two of the key presentations during the workshop were:
Dr. Stadtmauer’s excellent overview of the role of salvage ASCT. The data from the International Bone Marrow Transplant Registry (IBMTR) were compared with other reported studies. Outcomes correlated with the length of the first remission with ASCT, as well as the depth of response with both the first and second (salvage) transplants. To put the results in perspective with regard to other potential therapies for relapsed patients, average remissions were about 1 year and subsequent overall survival for approximately 2-4 years.
Prof. Gordon Cook’s (University of Leeds, UK) presentation of the results of his Myeloma X Trial. Salvage transplant with melphalan 200mg/m2 (ASCT) was compared with simply Cytoxan by mouth (400 mg/m2 once/week for 3 months). Starting in 2008, 174 patients were randomized. The full results were published recently in Lancet Oncology. It was very helpful to see the benefit of salvage ASCT in this randomized setting. The data also confirmed the importance of the length of prior remission and depth of response.
After breaking into four workgroups, workshop participants presented their ideas and recommendations, which included:
- A need to summarize current knowledge
- Risk stratification of patients at relapse
- Assessment of the role of minimal residual disease (MRD) measurement after ASCT in the relapse setting
- Studies of ASCT at different time points
- A need for comparative effectiveness research (ASCT at relapse versus other options)
With priorities agreed upon by all of the workshop participants, the meeting concluded with a commitment to prepare guidelines promptly under the auspices of the IMWG and also to set up several planned studies. The IMF team of Lisa Paik, Diana Wang and myself were very pleased to be in attendance and will be working closely with the transplant team members to ensure rapid progress to achieve the planned outcomes. In addition, follow up meetings will occur as feasible at the Annual Meeting of the American Society of Hematology (ASH), the IMWG Summit and other venues.
So, as always, stay tuned.
Dr. Brian G.M. Durie serves as Chairman of the International Myeloma Foundation and serves on its Scientific Advisory Board. Additionally, he is Chairman of the IMF's International Myeloma Working Group, a consortium of nearly 200 myeloma experts from around the world. Dr. Durie also leads the IMF’s Black Swan Research Initiative®.