Survival Outcome of Salvage Therapy with Second-Generation Novel Agents in Patients with Relapsed and Refractory Multiple Myeloma in Routine Clinical Practice

Survival outcome of patients with multiple myeloma (MM) has been markedly improved by the introduction of novel agents such as bortezomib, thalidomide, and lenalidomide over the past decade. Recent clinical studies have shown further improvement by second-generation agents, namely carfilzomib, ixazomib, pomalidomide, elotuzumab, and daratumumab. However, the prognosis of patients who became refractory to both bortezomib and lenalidomide was extremely poor, and the efficacy of the second-generation agents in such patient remains unclear in routine clinical practice. In this study, we analyzed the outcome of MM patients in terms of overall survival (OS) and survival time after salvage therapy. A total of 174 patients (89 male and 85 female) treated between 2003 and 2017 were enrolled. The median age was 69 years old (range 35-89). The type of M protein was IgG in 93, IgA in 35, IgD in 10, Bence Jones type in 30, and non-secretory type in 5 patients, respectively. The international staging system (ISS) stages I, II, and III were 32, 66, and 63 patients, respectively. There were 100 patients with normal serum LDH and 39 with high LDH. As for initial therapy, 62 patients were treated with conventional chemotherapy, 83 with bortezomib-based regimens, 7 with lenalidomide-based regimens, and 22 with bortezomib + lenalidomide + dexamethasone. Forty-seven patients received autologous stem cell transplantation in the upfront setting. During the observation period 120 patients relapsed and 6 were refractory to initial therapy, and 38 patients were treated with conventional chemotherapy and 58 with the first-generation novel agents such as bortezomib, lenalidomide, or thalidomide as salvage therapy. The remaining 30 patients were further treated with the second-generation novel agents such as carfilzomib in 21, ixazomib in 5, pomalidomide in 6, elotuzumab in 4, or daratumumab in 8 patients after refractory to bortezomib and lenalidomide. The median progression-free survival was 17.7 months and the median OS was 51.0 months from initial therapy. Regarding the outcome according to salvage therapy, the median OS was 22.0 months for conventional chemotherapy group, 46.4 months for first-generation agent group, and 98.7 months for second-generation agent group (p