Daratumumab as Single Agent in Relapsed/Refractory Myeloma Patients: A Retrospective Real-Life Survey

Abstract

BackgroundThe anti-CD38 monoclonal antibody daratumumab is approved as a single agent for the treatment of patients with relapsed/refractory multiple myeloma (RRMM) who received at least three prior lines of therapy, including proteasome inhibitor and immunomodulatory agent. A retrospective multicentric study was designed to evaluate feasibility, tolerability, and efficacy of daratumumab in monotherapy in RRMM.MethodsThis study included 44 consecutive RRMM patients that underwent daratumumab monotherapy after a median number of four prior therapies (range 2–9). Patients were treated in seven Sicilian centers, as part of Sicilian Myeloma Network and three Calabrian centers outside of controlled clinical trials from August 2016 through July 2020.ResultsThe regimen was well tolerated with few grade 3–4 haematological and rare non-haematological adverse events, such as pneumonia. Definitive discontinuation was due to disease progression in 25 (57%) patients. Since three patients did not complete at least one full cycle, a total of 41 patients was evaluated for response. Overall response rate was 37%, and the disease control rate (stable disease or better) was high (73%). The best achieved responses within 6 months were very good partial remission or better (27%), partial remission (10%), minimal response (14%) and stable disease (22%). After a median follow up of 7.8 months, median progression free survival (PFS) was 7.2 months and overall survival (OS) 7.8 months. Univariate analysis showed that patients with PR or better after 6 months of therapy had longer median PFS and OS (respectively 29.5 vs 3.6 months, p=0.0001 and 30.6 vs 3.9 months p=0.0001), confirmed by multivariate analysis. Furthermore, standard cytogenetic risk and biochemical relapse type had prolonged median PFS, but not OS (respectively unreached vs 2.6, p=0.03 and 23.9 vs 6.2, p=0.05) in both univariate and multivariate analysis. Additionally, univariate analysis showed that patients treated with carfilzomib-lenalidomide-dexamethasone prior to daratumumab had significantly shorter PFS compared to pomalidomide-dexamethasone (3.4 months vs 9.3 months, p=0.03), that multivariate analysis failed to confirm.ConclusionsOur findings indicate that daratumumab as single agent is safe and well-tolerated regimen in real-life, associated to prolonged PFS and OS in responding patients. No new safety signals were identified.

Lenalidomide-based triplet regimens in first relapsed multiple myeloma patients: real-world evidence from a propensity score matched analysis

“…(18,19,38) Collection of data regarding anti-CD38 MoAb Daratumumab are more limited, often focusing on its use as single agent in more advance RRMM patients. (39,40) The few RWD on DaraRd found gaps in terms of response rate and PFS with respect to POLLUX trial, largely attributed to higher rate of baseline adverse prognostic factors like multiple comorbidities, advanced disease phases, lenalidomide refractoriness. (16,41) The population of our study had some homogeneous baseline characteristics (all patients were treated in first relapse, they were not primary refractory, and were mostly lenalidomide naïve), that could represent the clinical setting for better evaluating the real-life performances of DaraRd as well as KRd, and partly helps in limiting the well-known persistent bias of a retrospective analysis.…”

“…Collection of data regarding anti-CD38 MoAb daratumumab are more limited, often focusing on its use as a single agent in more advance RRMM patients. 39 , 40 …”

Novel Therapies in BCMA-exposed Relapsed/Refractory Multiple Myeloma: The Anti-BCMA Therapy-refractory Patient

“…Daratumumab is a human monoclonal antibody that binds CD38-expressing PCs, thus inducing tumour cell death through antibody-dependent cell-mediated cytotoxicity, antibody-dependent phagocytosis, apoptosis and complement-dependent cytotoxicity. 27…”

“…GPRC5D is a therapeutically targeted type-C7 transmembrane protein expressed on the surface of CD138+ malignant PCs. 27,28 Levels of GPRC5D mRNA are elevated in patients with myeloma phenotypes and are correlated with high-risk PC malignancies, making this a promising target for T-cell-mediated killing. 29 Though both BCMA and GPRC5D surface receptors are present in a majority of MM cell lines, GPRC5D expression is heterogeneous and independent of BCMA expression.…”

Spotlight on Melphalan Flufenamide: An Up-and-Coming Therapy for the Treatment of Myeloma

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] In this respect, the first and subsequent treatment lines are enriched with a suitable combination of these novel agents in doublets, triplets, and quadruplets, with proper class shift scheduling. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] Novel chimeric antigen receptor (CAR) T cell-based therapies, 17 along with anti-B-cell maturation antigen (BCMA) antibody-drug conjugates, bispecific antibodies, and bispecific T cell engagers (BiTEs), 18 produce renewed expectation for MM patients. Novel antibody constructs, such as belantamab mafodotin, 19 can be considered after repeated relapses.…”