Single agent daratumumab in advanced multiple myeloma possesses significant efficacy even in an unselected "real-world" population

Abstract

Objective. The treatment of relapsed and refractory multiple myeloma (RRMM) remains challenging. The outcomes in highly pretreated populations are unsatisfactory and there is urgent need for novel and safe therapeutic approaches. Recently, daratumumab has been approved for RRMM with promising results even in monotherapy. The aim of this study was to assess the efficacy of single agent daratumumab outside a clinical trial. Patients and Methods. 14 patients with RRMM and significant pretreatment (median 4.5 previous lines) entered a specific healthcare program and received treatment with single agent daratumumab. They were followed for therapeutic response based on IMWG criteria, and incidence of adverse events. The data were collected using the Registry of Monoclonal Gammopathies. Results. The overall response rate was 38.5%. 23.1% of patients reached very good partial response, 15.4% reached partial remission, 15.4% had minimal response, 38.5% had stable disease and 7.7% had progressive disease. The median progression free survival was 4.6 months and median overall survival was not achieved. The toxicities were mostly mild, only infectious complications and hematological toxicity reached grade III. Conclusion. We conclude that daratumumab has significant activity in highly pretreated RRMM even as a single agent, with an acceptable toxicity profile and survival impact.

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

“…As for the drug's safety profile, therapy was well tolerated with less than one third of cohort with grade 3-4 hematological (anemia, platelet reduction) and around one fifth having nonhematological AEs, that were in line with the results of GEN501 and SIRIUS (8,9). Regarding the infectious AEs, compared to other real-life studies, the incidence of grade 3-4 events was lower (31)(32)(33)(34)(35). We can hypothesize that the use of antiviral and antibiotic prophylaxis, together with on demand G-CSF supportive therapy could have been of aid in reducing the incidence of infectious complications, similar to our previous real-life experience with Poma-Dex (44) and KRd regimen (40).…”

“…On the other hand, real-life studies on daratumumab evaluated the efficacy and tolerability in overall population, thus elaborating the drug's every-day use. Even though different population studies had significant variation in patient size, double-refractory status and follow-up (31)(32)(33)(34)(35), ORR and PFS described in the majority of real-life studies were at least equal, if not superior compared to clinical trials ( Table 5, Supplementary Materials) (30).…”

Daratumumab monotherapy for relapsed/refractory multiple myeloma, focussed on clinical trial‐unfit patients and subsequent therapy

“…We believe that the trial‐unfit group significantly contributed to the poor PFS1 and had more cases that required the interruption of DM due to fatal infections. Comparing our present data and other real‐world DM data, using a relatively small and single‐centre patient series, 19–22 our present data included higher proportions of patients who had discontinuation of treatment due to severe AEs. The inclusion of these patients seemed to underlie the relatively poor survival outcomes, despite a higher ORR of 42·1%.…”

The late extramedullary relapse of the multiple myeloma with a predominant lesion of the duodenum and pancreas (clinical observation and mini-review)

“…Перспективным в лечении ЭП у пациентов с ММ может стать применение даратумумаба, антитела против CD38, эффективность и безопасность которого подтверждены в клинических исследованиях у пациентов с рецидивирующей и рефрактерной ММ, в том числе с внекостными поражениями [38][39][40][41]. Другие антитела, такие как анти-CD38-антитело изатуксимаб и анти-SLAMF7 элотузумаб, также продемонстрировали значительную эффективность в терапии резистентной или рефрактерной ММ, в связи с чем можно ожидать их успешного применения и при ЭП [42,43].…”