Phase II clinical and correlative study of carfilzomib, lenalidomide, and dexamethasone (CRd) in newly diagnosed multiple myeloma (MM) patients.

e18568 Background: Carfilzomib (Cz) is an irreversible proteasome inhibitor with potent anti-MM effects and decreased peripheral neuropathy rates compared to bortezomib. In this two-stage phase II trial of 45 planned patients, we treat newly diagnosed MM patients with Cz, lenalidomide(Ln), and dexamethasone (Dx). Methods: Eight 28-day cycles of induction comprises of Cz IV 20/36 mg/m2 on days 1, 2, 8, 9, 15, 16; Ln oral 25 mg days 1-21; and Dx IV/oral 20/10 mg on days 1, 2, 8, 9, 15, 16, 22, 23. Transplant eligible patients undergo stem cell collection after 4 cycles of CRd and continue with induction. After 8 cycles of induction, patients with SD or better receive 12 cycles of Ln maintenance 10 mg days 1-21. Primary endpoint is ≥ grade 3 neuropathy. Bone marrow samples are collected at baseline, C1D2 (single agent Cz exposed), CR/end of cycle 8 (cycles 1-8), and CR/end of cycle 21 (cycles 9-21). Patients are evaluated for clinical biomarkers and MRD studies (flow cytometry, PCR, and FDG PET-CT) at regula...