Bortezomib As Induction Before Autologous Transplantation, Followed by Lenalidomide As Consolidation-Maintenance in Untreated Multiple Myeloma Patients

Abstract

PURPOSE To evaluate the effect of bortezomib as induction therapy before autologous transplantation, followed by lenalidomide as consolidation-maintenance in myeloma patients. PATIENTS AND METHODS Newly diagnosed patients age 65 to 75 years were eligible. Induction (bortezomib, doxorubicin, and dexamethasone [PAD]) included four 21-day cycles of bortezomib (1.3 mg/m(2) on days 1, 4, 8, and 11), pegylated liposomal doxorubicin (30 mg/m(2) on day 4), and dexamethasone (40 mg/d; cycle 1: days 1 to 4, 8 to 11, and 15 to 18; cycles 2 to 4: days 1 to 4). Autologous transplantation was tandem melphalan 100 mg/m(2) (MEL100) and stem-cell support. Consolidation included four 28-day cycles of lenalidomide (25 mg/d on days 1 to 21 every 28 days) plus prednisone (50 mg every other day), followed by maintenance with lenalidomide (LP-L; 10 mg/d on days 1 to 21) until relapse. Primary end points were safety (incidence of grade 3 to 4 adverse events [AEs]) and efficacy (response rate). Results A total of 102 patients were enrolled. In a per-protocol analysis, after PAD, 58% of patients had very good partial response (VGPR) or better, including 13% with complete response (CR); after MEL100, 82% of patients had at least VGPR and 38% had CR; and after LP-L, 86% of patients had at least VGPR and 66% had CR. After median follow-up time of 21 months, the 2-year progression-free survival rate was 69%, and the 2-year overall survival rate was 86%. During induction, treatment-related mortality was 3%; grade 3 to 4 AEs included thrombocytopenia (17%), neutropenia (10%), peripheral neuropathy (16%), and pneumonia (10%). During consolidation-maintenance, grade 3 to 4 AEs were neutropenia (16%), thrombocytopenia (6%), pneumonia (5%), and cutaneous rash (4%). CONCLUSION Bortezomib as induction before autologous transplantation, followed by lenalidomide as consolidation-maintenance, is an effective regimen.

Autologous stem cell transplantation in elderly patients with multiple myeloma: evaluation of its safety and efficacy

“…Two phase II trials have consolidated the induction treatment -with four cycles of bortezomib, pegylated liposomal doxorubicin and dexamethasone -with tandem ASCT (each 100mg/m2 of melphalan), followed by consolidation therapy with four cycles of lenalidomide and prednisone, and a maintenance therapy with lenalidomide alone in patients aged 65-75 years [35,36]. The median PFS was 48 months, and the 5-year overall survival (OS) was 63%; notably, patients achieving a CR had a 5-year OS of 83%.…”

Management of older adults with multiple myeloma

“…In the first study, conducted in patients aged 65 to 70 years, Mel100 followed by ASCT led to longer median event-free survival (EFS) (28 months vs. 16.4 months; p < 0.001) and OS (58 months vs. 37.2 months; p < 0.001) compared with melphalan-prednisone (MP). 25 The second study compared MP, MP plus thalidomide (MPT) and Mel100 followed by ASCT in patients aged 65-75 years. MPT induced longer PFS and OS in comparison with both MP and Mel100, while no differences were observed between MP and Mel100.…”

Cyclophosphamide, thalidomide, and dexamethasone as induction therapy for newly diagnosed multiple myeloma patients destined for autologous stem-cell transplantation: MRC Myeloma IX randomized trial results

“…The assumption of no treatment interaction for both PFS (P=0.71) and OS end points was valid (P=0.74), and CTD was non-inferior to CVAD for PFS and OS. In the per-protocol analysis, the median PFS [95% CI] was 27 months ( [24][25][26][27][28][29]; range 0-73 months) in the CTD group and 25 months ( [23][24][25][26]; range 0-72 months) in the CVAD group (HR 0.94;]; P=0.56) (Figure 2A (Figure 2B). …”

“…The 33% of patients in the study who did not proceed to HDT/ASCT and who were progression-free after one year had a median PFS of 25 months (95% CI [21][22][23][24][25][26][27][28][29]; those who were alive at one year had a median OS of 50 months (95% CI 46-63). After adjustment for age, these outcomes were identical to those for elderly patients treated in the non-intensive pathway of the MRC Myeloma IX study.…”