Novel Agents and Autologous Stem Cell Transplantation Improve Survival of Multiple Myeloma Patients with Ages 65–70 Years: A Multicenter Retrospective Collaborative Study Between Japanese Society of Myeloma and European Myeloma Network

Abstract 5030

With the emergence of novel agents, the treatment paradigm of multiple myeloma (MM) has changed dramatically in the last decade. Although there have been many attempts to improve the outcome by using novel agents as first-line and/or salvage therapies, it is not clear whether the combined use of novel agents with autologous stem cell transplantation (SCT) has translated into better outcome for elderly patients with MM. To clarify this issue, we retrospectively analyzed the clinical features and treatment outcome of patients with ages 65–70 (median 67) years. From January 2004 to December 2009, a total of 318 patients (167 male and 151 female) were treated in 38 centers in Japan and Italy. The monoclonal immunoglobulin (Ig) was IgG in 169 patients, IgA in 80, light chain in 56, IgD in 7, and others in 6, respectively. Twenty-two patients were classified as Durie & Salmon stage I, 77 were stage II, and 212 were stage III, respectively. As for the International Staging System (ISS), 86 patients were in ISS stage I, 107 were in ISS stage II, and 102 were in ISS stage III, respectively. Treatment for each patient was determined by a physician-in-charge. As initial therapy, 192 patients were treated with conventional chemotherapy; melphalan and prednisone (MP) in 78, vincristine, adriamycin, and dexamethasone (VAD) in 56, and other regimens in 58, respectively. Eighty-eight patients were treated with novel agent-containing regimens composed of bortezomib in 62, lenalidomide in 17, and thalidomide in 9, respectively. Twenty-one patients were treated with conventional chemotherapy (VAD) plus SCT, and 17 were with novel agents (bortezomib and dexamethasone) plus SCT. The median progression-free survivals (PFS) of the 4 different treatment groups were 19. 1 months, 24. 5 months, 26. 8 months, and 35. 2 months, respectively, and there was a significant improvement in the groups with novel agents (p=0. 006) and novel agents plus SCT (p=0. 032) compared with the conventional chemotherapy group. The median overall survival (OS) of the conventional chemotherapy group was 46. 0 months, while those of other groups were not reached. When compared with the outcome of the conventional chemotherapy group, there was a significant improvement in OS in the groups with novel agents (p=0. 001), chemotherapy plus SCT (p=0. 02), and novel agents plus SCT (p=0. 02), and novel agents plus SCT resulted in the best OS (88% at 6 years). Best responses to treatment of 318 patients were as follows: complete response (CR) in 26 patients (8. 2%), very good partial response (VGPR) in 56 (17. 6%), partial response (PR) in 127 (39. 9%), stable disease (SD) in 92 (28. 9%), and disease progression (PD) in 17 (5. 3%), respectively. Significant differences in OS were found between CR and PR groups (p=0. 002) and between VGPR and PR groups (p=0. 045). In 168 relapsed patients after initial treatment, 148 patients were treated with novel agent-containing regimens and the median OS from the time of relapse was 45. 5 months compared with 15. 0 months for 20 patients treated with conventional chemotherapy alone (p=0. 03). In a multivariate analysis using stepwise selection, IgG or IgA type (p=0. 013), normal serum albumin (p<0. 0003), ISS 1–2 (p=0. 004), and the use of novel agents (p=0. 002) were independent prognostic factors significantly associated with better OS. These results indicate that first-line autologous SCT prolongs OS compared with conventional chemotherapy alone and induction therapy with novel agents has a major impact on OS with or without autologous SCT. Thus, combination with novel agents and autologous SCT may improve outcome even in this subgroup of patients with MM.