PS1396 RESULTS OF PHASE I/II STUDY OF NIVOLUMAB WITH AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION IN MULTIPLE MYELOMA PATIENTS WITH SUBOPTIMAL RESPONSE TO PRIMARY INDUCTION THERAPY
Authors: O. Pirogova, E. Darskaya, V. Porunova, O. Kudyasheva, E. Babenko, N. Mikhailova, B. Afanasyev
Journal: HemaSphere (2019)

Background: Several treatment options are available for patients with newly-diagnosed multiple myeloma (NDMM) who are transplant ineligible. Most recently, the ongoing ALCYONE and MAIA studies demonstrated significant improvement in progression-free survival (PFS) and overall response rate (ORR) for treatment with daratumumab plus bortezomib, melphalan, and prednisone (D-VMP) vs. VMP alone, and for treatment with daratumumab plus lenalidomide and dexamethasone (D-Rd) vs. Rd continuous alone, respectively (1,2). In the absence of randomized control trials (RCTs) vs. other relevant comparators, a network meta-analysis (NMA) is needed to support evidence-based decision making and ultimately help to optimize treatment and outcomes of patients with NDMM who are transplant ineligible (3). Aims: This NMA compares daratumumab (D)-based regimens with other relevant comparators for the frontline treatment of patients with NDMM who are ineligible for transplantation. Methods: A systematic literature review was conducted based on PubMed, EMBASE, Cochrane, the American Society of Hematology (ASH), American Society of Clinical Oncology (ASCO) and ESMO. Additional meta-analyses/reviews and ClinicalTrials.gov were further searched for potential publications that were not included in the search engines up to Dec 2018. Efficacy outcomes (i.e. the hazard ratio [HR] and 95% confidence interval [CI] for progression-free survival [PFS] and odds ratio [OR] for overall response rate [ORR]) were extracted and synthesized in an NMA. Choice of model was made on lowest deviance information criterion (DIC). Lenalidomide and dexamethasone (Rd) continuous was selected as comparator for this analysis as it was commonly included in the guidelines across regions. For PFS, HR <1 indicates the comparison is not in favor of Rd continuous whereas OR <1 is in favor of Rd continuous for ORR. Results: Random effects results for both PFS and ORR against Rd continuous are presented in Table 1. For PFS, D-based regimens are the most favorable regimens compared to all other relevant treatment options. Compared to Rd continuous, the HR of PFS of D-VMP is 0.62 (0.21–1.84) and the HR of PFS of D-Rd is 0.55 (0.30–0.99). For PFS, in addition to the D-based regimens, VMPT-VT 0.84 (0.28–2.47) and ERd 0.83 (0.22–3.04) are the only other options that are more favorable than Rd continuous, the performance of other treatment options is less favorable than Rd continuous. Similar patterns are observed with ORR.Summary/Conclusion: The NMA demonstrated favorable efficacy outcomes for D-based regimens including D-Rd and D-VMP vs. other relevant front-line options for patients with NDMM who are transplant-ineligible. A limitation of this analysis was that VRd, a regimen recommended by key treatment guidelines (4,5) for patients with NDMM who are transplant-ineligible, was not included as appropriate data on VRd treatment in this patient population was not available to enable inclusion into the current NMA.