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Response to Novel Drugs before and after Allogeneic Stem Cell Transplantation in Patients with Relapsed Multiple Myeloma

2019; Elsevier BV; Volume: 25; Issue: 9 Linguagem: Inglês

10.1016/j.bbmt.2019.04.026

1523-6536

Lucía López‐Corral, Teresa Caballero‐Velázquez, Oriana López‐Godino, Laura Rosiñol, Sabina Pérez-Vicente, Francesc Fernández‐Avilés, Isabel Krsnik, Daniel Morillo, Inmaculada Heras, Mireia Morgades, J. Rifón, Antònia Sampol, Francisca Iniesta, Enrique M. Ocio, Jesús Martín, Montserrat Rovira, Martín Cabero, Cristina Castilla‐Llorente, Josep‐María Ribera, Marta Torres-Juan, José M. Moraleda, Carmen Martı́nez, Alejandro Vázquez, Gonzalo Gutiérrez, Dolores Caballero, Jesús F. San Miguel, María‐Victoria Mateos, José Antonio Pérez‐Simón,

Hematopoietic Stem Cell Transplantation

Highlights•Treatment regimens based on proteasome inhibitors and immunomodulatory drugs are effective and safe after allogeneic hematopoietic stem cell transplantation (HSCT).•Similar responses to these regimens are achieved in the pre-HSCT and post-HSCT settings.•Chronic graft-versus-host disease is associated with improved overall survival after relapse.•Time to relapse after allogeneic HSCT discriminates patients with very different outcomes.ABSTRACTMultiple 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.