Treatment Protocols for Patients With Multiple Myeloma Who Relapse After Transplant
While most patients with multiple myeloma will achieve disease control with autologous stem cell transplant (ASCT), virtually all of these individuals will relapse or progress and, therefore, will require further treatment. Oncologists have numerous effective treatment combinations at their disposal, and treatment choice depends on each specific clinical scenario.
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“I do not distinguish between post-transplant relapse and other relapses. Relapse is relapse, and we have numerous effective treatment combinations at our disposal, depending on the clinical scenario."
Research shows that most patients with multiple myeloma achieve disease control with ASCT; however, virtually all of these patients subsequently will relapse or progress, requiring additional treatment. In the last 25 years, I have had only one patient achieve long-term remission after ASCT; in fact, she is still in complete remission after 21 years. All of my other patients have ultimately failed with ASCT. Although patients with multiple myeloma have some delay in their time to progression following a transplant, their overall survival is not improved. This lack of survival benefit despite delaying progression of disease may be partially due to the limitations of using conventional serum M-protein and serum free light chains to monitor for progression. That is, our current methods of monitoring do not detect progression when the disease is worsening, but at a level that is undetectable using conventional serum and urine markers.
There is a spectrum of different perspectives on ASCT for multiple myeloma, ranging from the most ardent proponents to those who believe that it should almost never be used, and I would include myself in the latter group. I do not currently recommend ASCT for any of my patients unless they have no other option, as the procedure compromises my ability to effectively treat these individuals in the future. For example, if patients do not recover their functional status from a transplant, one of the limiting factors becomes cytopenias. That, in turn, interferes with their ability to participate in clinical trials because their counts are not in a range that allows their participation. This can also happen in nontransplant patients.
I do not distinguish between post-transplant relapse and other relapses. Relapse is relapse, and we have numerous effective treatment combinations at our disposal, depending on the clinical scenario. These treatments include pomalidomide, carfilzomib, and ixazomib, among others, in addition to histone deacetylase inhibitors and monoclonal antibodies, including elotuzumab and daratumumab. Moreover, the rules of relapse treatment have changed; the fact that a drug stops working in a given patient does not necessarily mean that drug will not work again in the same patient—drugs can, in fact, be reused after a number of years if the multiple myeloma regains sensitivity. In addition, a patient who fails a drug in one combination may respond when that same drug is used in another combination. It is also possible that a patient who fails a drug in a given class will often respond to another drug in the same class. Patients who fail bortezomib often respond to another proteasome inhibitor, such as carfilzomib. Patients who fail lenalidomide may respond to pomalidomide. These findings greatly expand the therapeutic options for the treatment of patients with multiple myeloma.
Hari P, Mateos MV, Abonour R, et al. Efficacy and safety of carfilzomib regimens in multiple myeloma patients relapsing after autologous stem cell transplant: ASPIRE and ENDEAVOR outcomes. Leukemia. 2017;31(12):2630-2641.
Holstein SA, Richardson PG, Laubach JP, McCarthy PL. Management of relapsed multiple myeloma after autologous stem cell transplant. Biol Blood Marrow Transplant. 2015;21(5):793-798.
Lehners N, Becker N, Benner A, et al. Analysis of long-term survival in multiple myeloma after first-line autologous stem cell transplantation: impact of clinical risk factors and sustained response. Cancer Med. 2018;7(2):307-316.