Daratumumab in Indian Patients with Relapsed and Refractory Multiple Myeloma: A Prospective, Multicenter, Phase IV Study

Abstract

Aim:

To assess the safety and effectiveness of daratumumab monotherapy in Indian patients with relapsed/refractory multiple myeloma.

Methods:

In this prospective, multicenter, phase IV study, patients (aged ≥18 years) received intravenous daratumumab (16 mg/kg) in six cycles. Safety was the primary end point.

Results:

Of the 139 patients included, 121 (87.1%) experienced ≥1 treatment-emergent adverse events (TEAEs; 53 [38.1%] drug-related), 32 (23%) had ≥1 serious TEAEs (five [3.6%] drug-related) and 16 (11.5%) deaths were reported (one death [0.7%] was drug-related). Overall response rate was 26.3%; 62.7% of patients had stable disease. Median time to first response and median progression-free survival were 5.2 and 5.9 months, respectively. Functional status and well-being were improved.

Conclusion:

Daratumumab showed an acceptable and expected safety profile with consistent efficacy, providing a novel therapeutic option for relapsed/refractory multiple myeloma management in India.

Plain language summary

Daratumumab is a monoclonal antibody approved for the treatment of patients with relapsed/refractory multiple myeloma (RRMM). This study evaluated the outcome of daratumumab single therapy in Indian patients who were not cured with other drugs used for the same disease. 139 adult patients were included in this study from 15 institutes across India. Daratumumab (16 mg/kg) was diluted with 500 or 1000 ml of saline solution and given slowly through the intravenous route 16-times within 6 months. The study examined whether the safety profile and benefits of daratumumab reported in Indian patients were similar to those reported in the RRMM populations of other countries. The study found that most of the adverse events were not severe and could be easily treated by the study physician. 16 patients died (one might have been due to daratumumab treatment). Daratumumab treatment provided life support and recovery benefits to many patients. Daratumumab single therapy provides an appropriate and acceptable safety profile with no new adverse events and consistent benefits in RRMM patients.

Clinical Trial Registration: NCT03768960 (ClinicalTrials.gov), CTRI/2019/06/019546.

Tweetable abstract

This study demonstrated an acceptable and expected safety profile with consistent efficacy for daratumumab monotherapy in patients with relapsed/refractory multiple myeloma, providing a novel therapeutic option for myeloma management in India.

Keywords::

• adverse event
• clinical response
• daratumumab
• multiple myeloma
• overall response rate

Author contributions

All authors contributed to data analysis, drafting or revising of the article; provided final approval for the version to be published; and agreed to be accountable for all aspects of the work.

Acknowledgments

The authors thank Dr Pankaj Malhotra (PGIMER, Chandigarh, India), one of the investigators of this study.

Financial disclosure

This study was funded by Johnson & Johnson Pvt. Ltd, India. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

T Korde, M Rege, U Deb and J Dixit are employees of Johnson & Johnson Pvt. Ltd, India. The authors have no other competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing disclosure

Rabi Panigrahy, PhD provided writing assistance and The manuscript writing assistance was funded by Johnson & Johnson Pvt. Ltd, India. Sangita Patil, PhD, CMPP provided additional editorial support (both from SIRO Clinpharm Pvt. Ltd, India) for development of the manuscript.

Ethical conduct of research

The authors state that the study protocol and the informed consent form were approved by local institutional review boards or ethics committees, and the study was conducted in compliance with the Declaration of Helsinki and the International Committee on Harmonisation Good Clinical Practices and as per Schedule Y of the Drugs and Cosmetics Act in India. In addition, all patients provided a written informed consent form for participation in the study.

Data sharing statement

The authors certify that this manuscript reports original clinical trial data: NCT03768960, CTRI/2019/06/019546. The individual, de-identified participant data, including patient-level data, supporting documents and clinical study report will be available. The data will be available between 16 August 2022 and 31 December 2024. The data sharing policy of Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. The data will be available to qualified external researchers. Requests will be reviewed and approved by an independent review panel based on scientific merit. All data provided are anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. Requests for access to the study data can be submitted through the Yale Open Data Access (YODA) Project site at http://yoda.yale.edu.