The effects of different schedules of bortezomib, melphalan, and prednisone for patients with newly diagnosed multiple myeloma who are transplant ineligible: a matching-adjusted indirect comparison

Abstract

For patients with newly diagnosed multiple myeloma (NDMM) who are transplant ineligible, bortezomib-melphalan-prednisone (VMP) demonstrated superior efficacy based on the VISTA trial. In subsequent trials, twice-weekly bortezomib was limited to the first cycle or completely replaced with once-weekly bortezomib to reduce toxicity. Following a systematic literature review, the efficacy and safety of modified VMP schedules (pooled data from the once-weekly bortezomib VMP arm of the GIMEMA trial and the VMP arm of the ALCYONE trial) were compared to the VISTA schedule using naïve and unanchored matching-adjusted indirect comparison (MAIC). Median progression-free survival was similar between VISTA and modified VMP (20.7 months [95% CI, 18.4–24.3] vs 19.6 months [95% CI, 18.8–21.0]). Peripheral neuropathy was significantly reduced with modified VMP versus VISTA VMP (all grades: naïve, 32.1% vs 46.8% and MAIC, 32.1% vs 46.7%; both p < .0001). These findings support a modified VMP dosing schedule for patients with NDMM who are transplant ineligible.

Keywords:

• VMP
• multiple myeloma
• matching-adjusted indirect comparison

Author contributions

MAD and JH contributed to conception of study design, data acquisition and analysis/interpretation; MH, BH, and AL contributed to conception of study design and data analysis/interpretation; HG contributed to data acquisition and analysis/interpretation; WD contributed to conception of study design and data acquisition; PS contributed to data acquisition; JSM contributed to conception of study design; PH and M-VM contributed to data analysis/interpretation. All authors drafted and reviewed the manuscript, approved the final version, decided to publish this report, and vouch for data accuracy and completeness.

Disclosure statement

M-VM served as a consultant and on the board of directors or advisory committees for Amgen, GlaxoSmithKline, Celgene, Janssen, Takeda, and AbbVie; and received honoraria from Amgen, Celgene, Janssen, and Takeda. JS-M received honoraria from Janssen, Celgene, Amgen, Bristol-Myers Squibb, Novartis, Sanofi, and Roche. HG served as a consultant for Adaptive Biotechnology, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Sanofi, and Takeda; received research funding from Amgen, Bristol-Myers Squibb, Celgene, Janssen, Sanofi, Takeda, Chugai, Mundipharma, and Novartis; and received honoraria from Bristol-Myers Squibb, Celgene, Janssen, Chugai, Novartis, and ArtTempi. PS received honoraria and research funding from Amgen, Celgene, Janssen, Karyopharm, and Bristol-Myers Squibb. MAD received honoraria from Janssen, Celgene, Takeda, Amgen, and Bristol-Myers Squibb. BH received equity ownership and research funding from and is an employee of Ingress Health Nederland BV. MH is an employee of Ingress Health. WD, PH, AL, and JH are employees of Janssen.

Data availability statement

The data sharing policy of Janssen Pharmaceutical Companies of Johnson & Johnson is available at https://www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through the Yale Open Data Access (YODA) project site at http://yoda.yale.edu.

Additional information

Funding

This analysis was sponsored by Janssen Global Services, LLC. Medical writing and editorial support were provided by Tara Abraham, PhD, of MedErgy, and Victoria Atess, PhD, of Ashfield, part of UDG Healthcare, and were funded by Janssen Global Services, LLC.