A Prospective Phase 2 Study to Assess Immunophenotypic Remission after Lenalidomide-Based Induction Followed By ASCT and Lenalidomide Maintenance in Patients with Newly Diagnosed Multiple Myeloma

Introduction ASCT is the standard treatment in MM for eligible patients Patients and methods 69 out of 80 included patients proceeded to mobilization after induction with 3 cycles of RVD. Eleven patients (14%) were dropped out due to early toxicity (n=9) or early progression (n=2). The RVD cycle consisted of lenalidomide 25 mg/d po. on days 1-14, bortezomib 1.3 mg/m 2 sc. on days 1,4,8 and 11 and dexamethasone 20 mg po. on days 1-2, 4-5, 8-9 and 11-12. Additional nine patients were withdrawn before ASCT due to progression, so actually 60 patients received MEL200+ASCT and lenalidomide maintenance was planned to start three months after ASCT, 10 mg/d on days 1-21 in a 28-day cycle. The multiparameter flow cytometry (MFC) was analyzed from all patients with at least PR response. 53/60 patients have achieved the time-point of three months after ASCT and can be analyzed here. Median follow-up time is 52 (1−115) weeks. Results Forty-five gr 3-4 SAEs were documented in 39 patients during induction; most common were infections (pneumonia, bronchitis) and gastrointestinal disorders. The nine patients with early drop out due to toxicities had following adverse events: severe liver toxicity, amaurosis fugax, neutropenia, severe sepsis-syndrome with rash, simultaneous diagnosis of adenocarcinoma pulmonum, history of prostate cancer, two patients not eligible to ASCT due to infections and one patient died of hepatorenal syndrome. The overall response rate for RVD induction was 86% in intention-to-treat. The primary endpoint, IR, measured by 6-10 color MFC, was achieved at ASCT in 22/69 (32%) of patients who actually received the planned RVD induction and in 22/80 (28%) by intention-to-treat (ITT). The median sensitivity of MFC-MRD-negativity was Three months post-ASCT 24/53 (45%) of evaluable patients had IR with the median sensitivity of MFC-MRD-negativity The achievement of at least VGPR response or IR at ASCT predicts better outcome with estimated PFS of 23.8 months compared to 15.2 months of patients response worse than VGPR (p=0.001) and the respective figures for IR and non-IR are 24.7 and 17.2 months (p=0.016). Patients with t(4;14), t(14;16), n=9, had shorter median PFS (shorter than patients with del 17p), 12.8 months, compared to estimated 20.8 months of other patients (p=0.053). Conclusion One third (28%) of patients achieved an IR after RVD induction, which contrasts with only 14% of serological CR/sCR. This discrepancy most probably results from the rather slow kinetics of paraprotein disappearance. Thus, subsequential samples and sufficient follow-up time are mandatory in evaluation of paraprotein responses. The IR was still predicting favorable outcome and only one of these MFC-MRD negative but paraproteinpositive patients has so far relapsed. In spite of quite high initial IR rate the patients with high-risk cytogenetics relapse quite soon. RVD regimen seems not to overcome their poor prognosis, and these patients clearly need more individual treatment choices. Disclosures Silvennoinen: Amgen: Consultancy, Honoraria; Celgene: Research Funding; Janssen: Research Funding; Genzyme: Honoraria; Sanofi: Honoraria; Research Committee of the Kuopio University Hospital Catchment Area for State Research Funding, project 5101424, Kuopio, Finland: Research Funding. Siitonen: Novartis: Other: charges of EHA congress 2015; Pzizer: Other: charges of EAHAD congress 2015. Putkonen: Celgene: Honoraria; Amgen: Honoraria. Porkka: Celgene: Research Funding. Remes: Roche: Honoraria; Celgene: Honoraria; Janssen: Honoraria. Jantunen: Genzyme: Honoraria; Sanofi: Honoraria; Genzyme: Consultancy.