Dear Editor,
Pawlyn et al. offer a thoughtful recent commentary in Blood Cancer Journal on progression-free survival (PFS) as a surrogate endpoint for overall survival (OS) in multiple myeloma trials [1]. In the section discussing “the issue of competing risks,” authors discuss trials of autologous stem cell transplantation (ASCT). The authors write, “Prior studies of transplant have shown consistent PFS with ASCT, but OS benefit has been less clear.” In support of this point, the authors write that the EMN02 study, which compared post-induction intensification with autologous stem cell transplant (ASCT) to bortezomib-melphalan-prednisone (VMP), demonstrated PFS benefit with ASCT but “no significant difference in OS.” Authors cite the primary analysis of EMN02, which was published in June 2020 with median follow-up of 60.3 months [2]. Longer follow-up of EMN02, however, did demonstrate a significant OS benefit with early ASCT after median follow-up of 75 months, as reported at the 2020 ASH Annual Meeting, with a hazard ratio of 0.81 (95% CI 0.66–0.98, p = 0.034) [3]. The OS benefit with front-line ASCT in EMN02 is notable considering the substantial (63%) crossover to ASCT in later line therapy. EMN02 results therefore support an OS benefit to ASCT and a relationship between PFS and OS in ASCT trials.
Sincerely,
Alfred L. Garfall, MD
Acknowledgements
The author acknowledges support from a Leukemia & Lymphoma Society Scholar in Clinical Research Award.
Author contributions
ALG wrote the manuscript.
Competing interests
The author discloses the following relationships: Consulting (Abbvie, Regeneron, Johnson & Johnson, Novartis, Smart Immune, Bristol Myers Squibb, Gracell); DSMB service (Johnson & Johnson); research funding (Johnson & Johnson, Novartis, CRISPR Therapeutics).
Footnotes
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References
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