Refractory Multiple Myeloma – A Systematic Literature Review and Network Meta-analysis

Abstracts free light chain (iFLC) was 9080 mg/l (range 119-201000 mg/l). Treatment was bortezomib-based in 41 (82%): 22% received bortezomib+dexamethasone (VD), 42% VD+cyclophosphamide (VCD), 16% VD+thalidomide (VTD), 2% VD+doxorubicin (PAD); 9(18%) patients received non-bortezomib containing regimens. Twenty five (50%) patients became HD independent at a median of 158 days from start of therapy (range 4-336); age
65 years was associated with higher probability (75% vs 38%) and shorter time to dialysis independence (51 vs 336 days) (p¼0.027). Bortezomib-based triplets vs VD alone were associated with higher probability of HD independence (57% vs 27%; p¼0.06). Median survival is 29 months; early mortality (<2 months from start of therapy) was 16%, mostly due to infectious complications. On intent to treat, 64% of the patients achieved PR (CR:6%, VGPR: 32%, PR: 26%). At landmark analysis, patients who with PR within the first 2 months had higher HD independence rates (68% vs 27%, p¼0.004). At landmark analysis, discontinuation of HD was associated with a significant improvement in survival (median OS 63 vs 22 months for patients who remained on HD, p¼0.002) and was similar to that of the rest of MM patients (57 months). High dose therapy (HDT) followed by ASCT was performed in five patients while on dialysis; 4/5 became dialysis independent approximately one month after HDT. In conclusion, about 6% of NDMM present severe RF requiring HD but half of them can become HD independent and this chance increases with bortezomib-based triplet therapy, without the use of special filters, and independence from HD is associated with a significant improvement in prognosis.

PS-113 Efficacy and Safety of DaratumumabBased Regimens in Patients with Relapsed/Refractory Multiple Myeloma e A Systematic Literature Review and Network Meta-analysis Meletios Dimopoulos,1 Katja Weisel,2 Jonathan L. Kaufman,3 Pieter Sonneveld,4 Maria Rizzo,5 Yingxin Xu,5 Kyle Fahrbach,5 Maren Gaudig,6 Mary Slavcev,7 Annette Lam7 1

National and Kapodistrian University of Athens, Athens, Athens;

2

3

University Hospital of Tuebingen, Tuebingen, Germany; Winship

Cancer Institute of Emory University, Atlanta, GA; 4Erasmus MC Cancer Institute, Rotterdam, Netherlands; 5Evidera; 6Janssen-Cilag; 7

Johnson & Johnson

Introduction: Multiple myeloma (MM) is an incurable, lifelimiting disease that accounts for approximately 1% of all cancers and 13% of haematological malignancies. Daratumumab is a new monoclonal antibody aimed to improve outcomes in relapsed/refractory MM (RRMM), and has been investigated in combination with lenalidomide plus dexamethasone (DRd), POLLUX, and with bortezomib plus dexamethasone (DVd), CASTOR, in randomized controlled trials (RCTs). Although DRd and DVd have been compared against current standard of care (SOC), namely Rd, and Vd, it is not known how daratumumab plus SOC compares with other key treatment options available on the market. A systematic literature review (SLR) and

network meta-analysis (NMA) was therefore conducted to determine the comparative effectiveness of daratumumab plus SOC with other relevant options. Methods: An SLR based on searches of Medline, Embase, and the Cochrane Library was conducted to identify and then assess RCTs of treatments for RRMM. The specific studies of interest were those that had investigated the efficacy and safety of other treatment options considered to be comparators to DRd or DVd. Data from trials that met the SLR’s inclusion criteria and the most recent data from POLLUX and CASTOR were extracted and then included in a Bayesian NMA to allow for indirect comparison. Results: RCT data from the SLR, POLLUX (DRd vs. Rd) and CASTOR (DVd vs. Vd) allowed formulation of two evidence networks. Network 1 included DRd and other Rd-based treatment, and Network 2, contained DVd and other Vd-based treatments. Analysis using a fixedeffects model found that DRd had a high probability of improving progression free survival (PFS; 99.9% to 100%) and overall survival (OS; 80.0% to 91.9%) versus the following treatments:  Carfilzomib+Rd e PFS: hazard ratio (HR) 0.54, 95% credible interval (CrI) 0.37e0.78 and OS: HR 0.80, 95% Crl 0.50e1.28  Elotuzumab+Rd e PFS: HR 0.54, 95% CrI 0.37e0.80; and OS: HR 0.82, 95% Crl 0.51e1.30  Ixazomib+Rd e PFS: HR 0.50, 95% Crl 0.33 to 0.74; and OS: HR 0.70, 95% Crl 0.42 to 1.15. Also, DVd had a high probability of improving PFS (94.7% to 100%) and OS (80.2% to 95.7%) versus the following treatments:  Panobinostat+Vd e PFS: HR 0.57, 95% CrI to 0.39e0.81; and OS: HR 0.67, 95% Crl 0.42e1.06  Carfilzomib+dexamethasone e PFS: HR 0.74, 95% Crl 0.51e1.07; and OS 0.80, 95% Crl 0.48e1.34  Cyclophosphamide+Vd e PFS data not reported; OS HR 0.53, 95% Crl 0.23e1.23. Of note, OS data for daratumumab are not yet mature and are still being collected. Conclusion: Evidence suggests that the combinations of DRd and DVd are effective in improving PFS in patients with RRMM with similar trends found for OS when compared with other established and new regimens. The results indicate that daratumumab in combination with SOC may be considered an effective treatment option in this indication.

PS-114 (d) Final Survival Analysis From the FIRST Trial: Lenalidomide Plus Low-Dose Dexamethasone Until Progression (Rd Cont) v Melphalan, Prednisone and Thalidomide (MPT), and Rd for 18 Cycles (Rd18) for TransplantIneligible (TNE) Patients (Pts) With Newly Diagnosed Multiple Myeloma Thierry Facon,1 Meletios Athanasios Dimopoulos,2 Angela Dispenzieri,3 John Catalano,4 Andrew R. Belch,5 Michele Cavo6 1

Service des Maladies du Sang, Hôpital Claude Huriez, Lille, France;

2

National and Kapodistrian University of Athens, School of Medicine,

Athens, Greece; 3Mayo Clinic; 4Frankston Haematology and Oncology Center; 5Cross Cancer Institute; 6Bologna University School of Médicine, Seragnoli Institute of Hematology

16th International Myeloma Workshop March 1-4, 2017

- e63