Comparative Efficacy of Daratumumab Monotherapy and Pomalidomide Plus Low-Dose Dexamethasone in the Treatment of Multiple Myeloma: A Matching Adjusted Indirect Comparison.

Abstract

BACKGROUND:

Daratumumab (a human CD38-directed monoclonal antibody) and pomalidomide (an immunomodulatory drug) plus dexamethasone are both relatively new treatment options for patients with heavily pretreated multiple myeloma. A matching adjusted indirect comparison (MAIC) was used to compare absolute treatment effects of daratumumab versus pomalidomide + low-dose dexamethasone (LoDex; 40 mg) on overall survival (OS), while adjusting for differences between the trial populations.

MATERIALS AND METHODS:

The MAIC method reduces the risk of bias associated with naïve indirect comparisons. Data from 148 patients receiving daratumumab (16 mg/kg), pooled from the GEN501 and SIRIUS studies, were compared separately with data from patients receiving pomalidomide + LoDex in the MM-003 and STRATUS studies.

RESULTS:

The MAIC-adjusted hazard ratio (HR) for OS of daratumumab versus pomalidomide + LoDex was 0.56 (95% confidence interval [CI], 0.38-0.83; p = .0041) for MM-003 and 0.51 (95% CI, 0.37-0.69; p < .0001) for STRATUS. The treatment benefit was even more pronounced when the daratumumab population was restricted to pomalidomide-naïve patients (MM-003: HR, 0.33; 95% CI, 0.17-0.66; p = .0017; STRATUS: HR, 0.41; 95% CI, 0.21-0.79; p = .0082). An additional analysis indicated a consistent trend of the OS benefit across subgroups based on M-protein level reduction (≥50%, ≥25%, and <25%).

CONCLUSION:

The MAIC results suggest that daratumumab improves OS compared with pomalidomide + LoDex in patients with heavily pretreated multiple myeloma.

IMPLICATIONS FOR PRACTICE:

This matching adjusted indirect comparison of clinical trial data from four studies analyzes the survival outcomes of patients with heavily pretreated, relapsed/refractory multiple myeloma who received either daratumumab monotherapy or pomalidomide plus low-dose dexamethasone. Using this method, daratumumab conferred a significant overall survival benefit compared with pomalidomide plus low-dose dexamethasone. In the absence of head-to-head trials, these indirect comparisons provide useful insights to clinicians and reimbursement authorities around the relative efficacy of treatments.

• Authors: Suzy Van Sanden, Tetsuro Ito, Joris Diels, Martin Vogel, Andrew Belch, Albert Oriol
• Journal: The oncologist (Oncologist) Vol. 23 Issue 3 Pg. 279-287 (03 2018) ISSN: 1549-490X [Electronic] England
• PMID: 29192016 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © AlphaMed Press 2017.

Chemical References

• Antibodies, Monoclonal
• Myeloma Proteins
• multiple myeloma M-proteins
• daratumumab
• Thalidomide
• Bortezomib
• Dexamethasone
• pomalidomide
• Lenalidomide

Topics

• Aged
• Antibodies, Monoclonal (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Bortezomib (therapeutic use)
• Clinical Trials as Topic
• Dexamethasone (therapeutic use)
• Drug Resistance, Neoplasm
• Humans
• Lenalidomide (therapeutic use)
• Middle Aged
• Multiple Myeloma (drug therapy, mortality)
• Myeloma Proteins (metabolism)
• Survival Rate
• Thalidomide (analogs & derivatives, therapeutic use)
• Treatment Outcome