Daratumumab in Relapse/Refratory Multiple Myeloma: Real World Evidence from a Tertiary Center

Introduction: Daratumumab is an anti-CD38 monoclonal antibody, firstly approved in the relapsed/refractory multiple myeloma (R/R MM) setting, both in monotherapy and combination.

Several phase 3 trials have demonstrated the efficacy of Daratumumab in association with proteasome inhibitors (PI) or immunomodulator (IMiD) in this setting.

The aim of this study was to evaluate the efficacy and safety profiles of Daratumumab in patients (pts) with R/R MM diagnosed followed in a tertiary center.

Methods: Retrospective, single-center study, including pts with R/R MM treated with Daratumumab in monotherapy or in combination between 2017 and 2021 on a real life basis.

The diagnosis variables, response according to IMWG criteria and therapy safety profile according to CTCAE v5.0 were evaluated. High risk cytogenetic was defined as the presence of t(4;14), t(14;16), and/or del17p, assessed by fluorescence in situ hybridization (FISH).

The Kaplan-Meier method was used to estimate survival curves and the Cox proportional hazards model for univariate and multivare analysis (variables with p<0.15 in univariate analysis were included in the multivariate model).

Results: 74 pts, 50 male, were included, with a median age of 58 years (75.7% were younger than 65 years) and 86.5% had ECOG-PS 0-1. In the 39 pts with available cytogenetics, 17 (23.0%) presented with high risk features. Most pts (97.7%) were treated with a triplet, 53.7% with Lenalidomide (VRd), 19% with Pomalidomide (DPd), 3% with Carfilzomib (DKd) 2% with Bortezomib (DVd) and 1% with cyclophosphamide (DCyd). The median number of previous treatment lines was 1 (1-2).

The overall response rate was 82.4%, with 75.7% (n=56) achieving ≥VGPR and 20 (27.0%) pts undergoing autologous stem-cell transplant (ASCT),16 pts with first ASCT e four with second ASCT.

At a median follow-up of 30.5 months, the median progression-free survival (PFS) was 23.9 months and the median overall survival (OS) was 30.0 months. At 4 years, PFS and OS were 35.4% and 43.8%, respectively.

Pts with <65 years old had higher median PFS (30.5 vs 11.1 months, HR 0.5 [95%CI 0.3-1.1]; p=0.089) and OS (42.1 vs 16.0 months, HR 0.6 [95%CI 0.3-1.3]; p=0.221) compared with 65-74 years pts.

The median PFS and OS were not achieved in pts with standard cytogenetic risk and in high risk group were 12.1 and 28.3 months, respectively.

In the multivariate model, high risk cytogenetic was the only characteristic that retained prognostic significance for OS (HR 5.2 [95%CI1.3-19.9]; p=0.017).

The most common adverse effects were neutropenia (56.8%) and anemia (50.0%), and 37 (50%) pts had a grade 3/4 adverse event. In 6 (8.1%) pts, discontinuation of therapy was required due to unacceptable toxicity and 11 (14.9%) pts died during therapy with Daratumumab, one with progressive disease, three with infectious complications and in seven pts we were unable to access the cause of death.

Discussion: In our cohort, treatment with Daratumumab was an effective therapy in R/R MM, with most pts attaining ≥VGPR, with a quarter of them being able to undergo ASCT consolidation. PFS and OS were inferior comparing to the phase 3 trials CASTOR, CANDOR and POLLUX, but superior to that described in real-life studies of the Hungarian, Danish and Canadian groups. The main toxicities were hematological, but Daratumumab presented a reasonable safety profile, with a minority of pts needing to stop therapy due to toxicity

Geraldes:Celgene/BMS: Other: speaker fees; Pfizer: Other: Advisory boards; Sanofi: Other: Speaker fees, advisory boards; Takeda: Other: Speaker fees, advisory boards; Amgen: Other: Speaker fees, advisory boards; Janssen: Other: Speaker fees, advisory boards; Gilead: Other: Speaker fees, advisory boards.