The real-world outcomes of multiple myeloma patients treated with daratumumab

Abstract

Most patients cannot be included in randomized clinical trials. We report real-world outcomes of all Danish patients with multiple myeloma (MM) treated with daratumumab-based regimens until 1 January 2019. Methods Information of 635 patients treated with daratumumab was collected retrospectively and included lines of therapy (LOT), hematologic responses according to the International Myeloma Working Group recommendations, time to next treatment (TNT) and the cause of discontinuation of treatment. Baseline characteristics were acquired from the validated Danish Multiple Myeloma Registry (DMMR). Results Daratumumab was administrated as monotherapy (Da-mono) in 27.7%, in combination with immunomodulatory drugs (Da-IMiD) in 57.3%, in combination with proteasome inhibitors (Da-PI) in 11.2% and in other combinations (Da-other) in 3.8% of patients. The median number of lines of therapy given before daratumumab was 5 for Da-mono, 3 for Da-IMiD, 4 for Da-PI, and 2 for Da-other. In Da-mono, overall response rate (ORR) was 44.9% and median time to next treatment (mTNT) was 4.9 months. In Da-IMiD, ORR was 80.5%, and mTNT was 16.1 months. In Da-PI, OOR was 60.6% and mTNT was 5.3 months. In patients treated with Da-other, OOR was 54,2% and mTNT was 5.6 months. The use of daratumumab in early LOT was associated with longer TNT (p<0.0001). Patients with amplification 1q had outcome comparable to standard risk patients, while patients with t(4;14), t(14;16) or del17p had worse outcome (p = 0.0001). Multivariate analysis indicated that timing of treatment (timing of daratumumab in the sequence of all LOT that the patients received throughout the course of their disease) was the most important factor for outcome (p<0.0001). Conclusion The real-world outcomes of multiple myeloma patients treated with daratumumab are worse than the results of clinical trials. Outcomes achieved with daratumumab were best when daratumumab was used in combination with IMIDs and in early LOT. Patients with high-risk CA had worse outcomes, but patients with amp1q had similar outcomes to standard-risk patients.

Outcomes of daratumumab in the treatment of multiple myeloma: A retrospective cohort study from the Canadian Myeloma Research Group Database

“…While clinical trials demonstrate impressive benefit of darabased therapies, possible discordance with real-world practice might exist, as many patients in the real world are known to be ineligible for clinical trials. 22,23 A few small real-world multicentre studies specifically focusing on dara have been published, confirming the promising activity noted in clinical trials [23][24][25][26][27] [28][29][30][31] There remains a paucity of studies evaluating the outcomes of dara-containing regimens in larger realworld cohorts. Our study aimed to evaluate the impact of these regimens and to benchmark outcomes that may identify gaps that can be targeted for future optimization.…”

“…While clinical trials demonstrate impressive benefit of dara‐based therapies, possible discordance with real‐world practice might exist, as many patients in the real world are known to be ineligible for clinical trials 22,23 . A few small real‐world multicentre studies specifically focusing on dara have been published, confirming the promising activity noted in clinical trials 23‐27 (Atrash et al, 2021; Harvanová et al, 2021; Maouche et al, 2021; Szabo et al, 2021) 28‐31 . There remains a paucity of studies evaluating the outcomes of dara‐containing regimens in larger real‐world cohorts.…”

“…(Atrash et al, 2021;Harvanová et al, 2021;Maouche et al, 2021;Szabo et al, 2021). Additionally, many of these studies focused on patients receiving dara monotherapy[24][25][26][27] (Atrash et al, 2021; Maouche et al, 2021; Szabo et al, 2021…”

Putting the best foot forward when treating newly diagnosed multiple myeloma

“…treated fewer patients who had received more than three prior LOTs compared with SIRIUS and GEN501, likely accounting for the superior ORR, 44.9% and 42% respectively. Szabo reported, at second or third line, rates ≥very good partial response (VGPR) were 65.8% and 43.4% compared with 25% and 23.7%, at fifth and sixth LOTs respectively 8 . Lovas et al 10 .…”

High Expression of the Costimulatory Checkpoint Factor DNAM-1 by CD4+ T-Cells from Multiple Myeloma Patients Refractory to Daratumumab-Containing Regimens

“…Despite the multiple modes of action of DARA, the majority of patients receiving this antibody eventually relapse [ 16 ]. The mechanisms of resistance are poorly understood.…”