Response to Novel Drugs before and after Allogeneic Stem Cell Transplantation in Patients with Relapsed Multiple Myeloma.
Multiple myeloma (MM) remains as an incurable disease and, although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative approach, most patients ultimately relapse, and their treatment remains challenging. Because allo-HSCT can modify not only the biology of the disease, but also the immune system and the microenvironment, it can potentially enhance the response to rescue therapies. Information on the efficacy and safety of novel drugs in patients relapsing after allo-HSCT is lacking, however. The objectives of this study were to evaluate the efficacy and toxicity of rescue therapies in patients with MM who relapsed after allo-HSCT, as well as to compare their efficacy before and after allo-HSCT. This retrospective multicenter study included 126 consecutive patients with MM who underwent allo-HSCT between 2000 and 2013 at 8 Spanish centers. All patients engrafted. The incidence of grade II-IV acute graft-versus-host disease (GVHD) was 47%, and nonrelapse mortality within the first 100 days post-transplantation was 13%. After a median follow-up of 92 months, overall survival (OS) was 51% at 2 years and 43% at 5 years. The median progression-free survival after allo-HSCT was 7 months, whereas the median OS after relapse was 33 months. Patients relapsing in the first 6 months after transplantation had a dismal prognosis compared with those who relapsed later (median OS, 11 months versus 120 months; P < .001). The absence of chronic GVHD was associated with reduced OS after relapse (hazard ratio, 3.44; P < .001). Most patients responded to rescue therapies, including proteasome inhibitors (PIs; 62%) and immunomodulatory drugs (IMiDs; 77%), with a good toxicity profile. An in-depth evaluation, including the type and intensity of PI- and IMiD-based combinations used before and after allo-HSCT, showed that the overall response rate and duration of response after allo-HSCT were similar to those seen in the pretransplantation period. Patients with MM who relapse after allo-HSCT should be considered candidates for therapy with new drugs, which can achieve similar response rates with similar durability as seen in the pretransplantation period. This pattern does not follow the usual course of the disease outside the transplantation setting, where response rates and time to progression decreases with each consecutive line of treatment.
['López-Corral|Lucia|L|', 'Caballero-Velázquez|Teresa|T|', 'López-Godino|Oriana|O|', 'Rosiñol|Laura|L|', 'Pérez-Vicente|Sabina|S|', 'Fernandez-Avilés|Francesc|F|', 'Krsnik|Isabel|I|', 'Morillo|Daniel|D|', 'Heras|Inmaculada|I|', 'Morgades|Mireia|M|', 'Rifon|Jose J|JJ|', 'Sampol|Antonia|A|', 'Iniesta|Francisca|F|', 'Ocio|Enrique-María|EM|', 'Martin|Jesús|J|', 'Rovira|Montserrat|M|', 'Cabero|Martín|M|', 'Castilla-Llorente|Cristina|C|', 'Ribera|Josep-María|JM|', 'Torres-Juan|Marta|M|', 'Moraleda|Jose María|JM|', 'Martinez|Carmen|C|', 'Vázquez|Alejandro|A|', 'Gutierrez|Gonzalo|G|', 'Caballero|Dolores|D|', 'San Miguel|Jesús F|JF|', 'Mateos|María-Victoria|MV|', 'Pérez-Simón|Jose Antonio|JA|']
D000328:Adult D000368:Aged D064591:Allografts D018572:Disease-Free Survival D005260:Female D005500:Follow-Up Studies D006086:Graft vs Host Disease D018380:Hematopoietic Stem Cell Transplantation D006801:Humans D007155:Immunologic Factors D015994:Incidence D008297:Male D008875:Middle Aged D009101:Multiple Myeloma D061988:Proteasome Inhibitors D012008:Recurrence D012189:Retrospective Studies D013030:Spain D015996:Survival Rate
Multiple myeloma Allogeneic hematopoietic stem cell transplantation Allo-HSCT Proteasome inhibitor Immunomodulatory drug