PB2146 SINGLE AGENT DARATUMUMAB IN VERY ADVANCED RELAPSED/REFRACTORY MULTIPLE MYELOMA PATIENTS: A REAL‐LIFE SINGLE CENTER RETROSPECTIVE STUDY
Authors: Jullien M. , Trudel S. , Tessoulin B. , Mahé B. , Dubruille V. , Blin N. , Gastinne T. , Lok A. , Lebourgeois A. , Peterlin P. , Garnier A. , Chevallier P. , Guillaume T. , Thomaré P. , Le Gouill S. , Moreau P. , Touzeau C. 
Published: June 2019

Background:Daratumumab is approved as a single agent for the treatment of patients (pts) with relapsed and refractory multiple myeloma (RRMM) who have received at least three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent (IMID), or who are double refractory to a PI and an IMID. In this setting, the pooled analysis of the GEN501 and SIRIUS trials showed an overall response rate (ORR) of 31%, a median progression‐free survival (PFS) and overall survival (OS) of 4.0 and 20.1 months, respectively. To date, few real‐life data have reported the efficacy of single agent daratumumab in unselected advanced myeloma patients.Aims:To evaluate efficacy and tolerance of single‐agent daratumumab in advanced RRMM patients outside clinical trials.MethodsAll consecutive patients treated in our institution between April 2016 and April 2018 were included in this retrospective study if they fulfilled all the following criteria: (i) diagnosis of RRMM who have received at least three prior lines of therapy including a PI and an IMID, or who were double refractory to PI and IMID, (ii) treatment with single agent daratumumab (iii) outside clinical trials. The response categories were defined according to the International Myeloma Working Group consensus criteria. OS and PFS were estimated using the Kaplan‐Meier method. Safety was evaluated through the rate of infusion related reactions (IRR) and adverse events (AE).Results:41 consecutive pts were analyzed. The median age was 68 years, including 7 pts (17%) older than 75 years. Eight pts (20%) had ECOG performans status >2. Ten (24%) had high‐risk cytogenetic, and 13 (32%) had extra‐medullary disease. The median number of prior therapies was 4 (range 2‐9). All pts were previously exposed to PI and IMID, 59% were refractory to both PI and IMID and 95% refractory to IMID. All pts were refractory to the last line of therapy. The ORR was 24.4% (10/41), including 4.9% VGPR (2/41). At a median follow‐up time of 6.5 months, all pts had discontinued daratumumab because of disease progression. The median PFS was 1.9 months (CI 1.4‐2.5). For pts achieving partial response or better, the median PFS was 10.1 months (CI 8.3‐11.6). Median time to response for those patients was 1.2 months (CI 1.0‐1.8), and median response duration was 9.0 months (CI 4.6‐10.6). Median OS was 6.5 months (CI 3.1‐10.0). Twelve IRR occurred (29.3%) and mostly (11/12) consisted of grade 1‐2 reaction. Only one grade 4 IRR occurred needing permanent discontinuation of the drug. Others AE mostly (>20%) consisted of infections, anemia and thrombocytopenia, with no new safety signal identified.Summary/Conclusion:This real‐life study demonstrated favorable safety profile but modest clinical efficacy of daratumumab monotherapy in very advanced unselected RRMM patients.