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

Jiri Minarik,Tomas Jelinek,Vladimir Maisnar,Lucie Brozova,Petra Krhovska,Petra Krhovska,Vlastimil Scudla,Vlastimil Scudla,Ludek Pour,Ivan Spicka,Roman Hajek,Alexandra Jungova

doi:10.5507/bp.2018.064

Abstract

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. 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. 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. We conclude that daratumumab has significant activity in highly pretreated RRMM even as a single agent, with an acceptable toxicity profile and survival impact.

Highlights

Daratumumab (DARA) is an anti-CD38 monoclonal antibody recently introduced in the treatment of relapsed or relapsed and refractory multiple myeloma (MM)
DARA was approved based on a phase II clinical trial (SIRIUS) as a breakthrough therapy, which is quite rare as most drugs have to confirm their efficacy in phase III trials
The unique mechanism of action via immune-mediated mechanisms provides a novel therapeutic approach with effect in highly pre-treated refractory populations with myeloma clone resistant to other therapies

Summary

Introduction

Daratumumab (DARA) is an anti-CD38 monoclonal antibody (mAb) recently introduced in the treatment of relapsed or relapsed and refractory multiple myeloma (MM). DARA targets myeloma cells via a variety of immune-mediated mechanisms including complementdependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity, antibody-dependent cellular phagocytosis and direct apoptosis with crosslinking[1,2]. DARA was originally chosen from a large panel of anti-CD38 mAbs because of its ability to trigger complement-dependent cytotoxicity[3]. Another mechanism of action – immunomodulatory – has recently been discovered. This though still not fully understood, is probably based on depletion of CD38+ immune suppressive cells such as Tregs, Bregs or myeloid derived suppressor cells[1].

Results

Discussion

Conclusion