S130 EXABS-242-CT The Continued and Often Underappreciated Benefits of Autologous Stem Cell Transplantation for Newly Diagnosed Multiple Myeloma (NDMM) Natalie S Callander, MD1,* 1University of Wisconsin, Madison, USA *Corresponding author: nsc@medicine.wisc.edu Keywords Autologous stem cell transplantation, melphalan, newly diagnosed myeloma Forty years ago, McElwain and colleagues proposed the use of high dose melphalan to treat newly diagnosed multiple myeloma, based on the results of a small 9 patient study, and ushered in a revolution in MM treatment.1 High dose melphalan with hematopoietic stem cell rescue was developed in an era where choices were few and survival of myeloma patients short, with less than 50% of patients surviving 3 years (SEER data). At the time of the first randomized phase III trial showing both a progression free and overall survival benefit for autologous bone marrow transplantation,2 considerable criticism emerged questioning the accuracy of the results.3 Since 1996, numerous other phase III trials have confirmed the value of autologous stem cell transplantation (ASCT) in improving progression free survival and in many cases overall survival.4,5 Yet it is logical to continue to assess the value of a procedure that is associated with considerable morbidity and occasional mortality, and with the continued development of the myeloma arsenal. The recently published DETERMINATION trial6 is the latest trial to exceed its predetermined endpoint of improved progression free survival, demonstrating a 53% reduction in progression or death, and a median PFS of 67.5 months versus 46.2 months among newly diagnosed transplant eligible multiple myeloma patients receiving bortezomib, lenalidomide and dexamethasone (RVD) with or without high dose melphalan and stem cell rescue. Moreover, the benefits of early ASCT were even more striking among standard risk patients, with a median PFS of 82.3 months (the longest ever reported to date in an upfront trial) versus 53.2 months for those receiving RVD only. Despite this unprecedented result, this study has been interpreted by some as proving the irrelevance of ASCT in more modern times. The chief arguments appear to be that the lack of overall survival benefit, and risk of secondary hematologic malignancies justify the abandonment of ASCT. However, this position does not take into account the many benefits that ASCT has delivered to patients for more than 3 decades. Although ASCT is associated with a period of increased morbidity, many patients report significant improvements in health related outcomes following transplantation. A small study from Biran et al noted significant improvements in pain and functioning beginning at 4 months post transplant.7 In DETERMINATION, the patient reported outcome, Global Health Score, showed a mean of 12.7% improvement among transplant recipients compared to only 3.5% improvement at 3 years (supplementary materials) among those treated with RVD. This lower benefit in the nontransplant arm is very much in keeping with what was observed among participants in the non-transplant MAIA trial, which reported only an 8.4% improvement after 1 year of therapy among patients receiving DRd.8 Another potential benefit of ASCT is the ability to keep patients’ MM well controlled and thus allow return to work. A survey conducted among MM patients who received ASCT, followed by either maintenance or observation, showed that 79% of those desiring to return to work were able to do so.9 In addition, a recent meta-analysis suggests that the use of maintenance therapy following ASCT is associated with improvements in QoL, compared to observation only.10 Most providers who treat MM patients regularly can point to the excellent quality of life in patients on maintenance, who require minimal in person follow up. An additional consideration is the impact of ASCT on outcomes in Black patients. It is now well known that MM disproportionately affects Black Americans at twice the incidence of white patients, and historically, Black patients have had lower rates of survival compared to non-Hispanic whites (SEER data, NCI 2019). One recent study conducted in the era of modern treatment found in a multivariate analysis examining risk factors for lower survival among Black MM patients, the only significant cause was lack of access to ASCT.11 Similarly, a retrospective analysis of Black versus White patients treated through the Veterans Administration, which provides equal access to care including ASCT, found improved outcomes among Black veterans compared to non-Hispanic whites,
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