Response-adapted lenalidomide–dexamethasone (LenDex) intensification after CyBorD induction for transplant-eligible multiple myeloma: the PIANO study

PURPOSE: Combination therapy with novel agents is the standard initial treatment for transplant-eligible patients with newly diagnosed multiple myeloma. However, the benefit of additional induction therapy for insufficient response remains unclear. This multicenter prospective study investigated response-adapted intensification with lenalidomide and dexamethasone (LenDex) after cyclophosphamide, bortezomib, and dexamethasone (CyBorD) in patients who did not achieve a very good partial response (VGPR) or better, followed by autologous stem cell transplantation (ASCT) and lenalidomide maintenance. METHODS: Sixty-three patients were enrolled at 10 centers between March 2014 and December 2017. RESULTS: Of the 63 patients, 44 underwent ASCT. Six patients (9.5% [6/63; 95% confidence interval, 3.6%-19.6%]) achieved complete response (CR) or better at 100 days post-ASCT; this rate was not higher than in the previous BD-based TUBA study. Best responses following ASCT and maintenance were stringent CR in 10 patients, CR in one, VGPR in 23, and partial response in eight. Three-year overall survival (OS) and progression-free survival (PFS) from induction were 90.0% and 43.9%, respectively. Thirty-one patients received LenDex before ASCT for insufficient response to CyBorD; 17 showed improved responses. OS and PFS from ASCT were comparable between patients treated with CyBorD alone and those receiving additional LenDex. CONCLUSION: The primary endpoint of CR or better at 100 days after ASCT was not improved compared with the historical BD-based TUBA study. However, response-adapted LenDex intensification was feasible, improved responses pre-ASCT in some patients, and resulted in post-ASCT outcomes comparable to those observed in patients who achieved sufficient responses with CyBorD alone.