Impact of omitting post-transplant minidose-methotrexate doses in allogeneic hematopoietic cell transplantation

Abstract

Given prophylactic methotrexate (MTX) is often held in the setting of toxicity we investigated the impact of omitting minidose-MTX dose(s). Outcomes were compared between patients who had 1–3 doses omitted and those who received all four planned doses of minidose-MTX. Of 370 consecutive patients, 50 had MTX dose(s) omitted. When MTX was omitted, initial management was mycophenolate mofetil (MMF; 36/50 patients) with or without corticosteroids (14/50 patients). Rates of grade 3–4 acute GVHD were similar between groups. Omission of minidose-MTX resulted in an increased risk of chronic GVHD (cGVHD; HR 2.27; p = .024) and decreased overall survival (HR 1.61; p = .024). However, other transplant-related outcomes were comparable. In summary, omission of minidose-MTX doses was not associated with an increased risk of acute GVHD when an alternative was added (e.g. MMF ± corticosteroids). This did not abrogate the increased risk of cGVHD or decreased overall survival.

Keywords:

• Hematopoietic stem cell transplantation
• graft-versus-host disease
• methotrexate
• mycophenolate mofetil

Disclosure statement

AL reports honoraria from Incyte, EUSA Pharma, and Medexus. CS receives research funding from Juno Therapeutics, Celgene/BMS, Bristol-Myers Squibb, Precision Biosciences, Actinium Pharmaceuticals, and Sanofi-Genzyme. He reports honoraria from Juno Therapeutics, Sanofi-Genzyme, Spectrum Pharmaceuticals, Novartis, Genmab, Precision Biosciences, Kite/Gilead, Celgene/BMS, Gamida Cell, Karyopharm Therapeutics, and GSK. BS receives research funding from Celgene/BMS. He reports honoraria from Gamida Cell, and Hansa Biopharma. MAP receives research funding from Incyte, Kite/Gilead, and Miltenyi. He reports honoraria from Abbvie, Bellicum, Bristol-Meyers Squibb, Celgene, Cidara Theraputics, Incyte, Kite/Gilead, Medigene, Miltenyi, MolMed, Nektar Therapeutics, NexImmune, Novartis, Omeros, Merck, and Servier. He serves on the advisory board for Cidara Therapeutics, Medigene, and Servier. SAG reports honoraria from Amgen, Actinium, Celgene, Janssen, Quintiles, Pfizer, CSL Behring, Sanofi, Adienne, Kite/Gilead, and Jazz Pharmaceuticals. He serves on the advisory board for Amgen, Celgene, Kite/Gilead, Jazz Pharmaceuticals, and Novartis. BG receives research funding from Actinium.

Additional information

Funding

This research was supported in part by National Institutes of Health award P01 CA23766 and NIH/NCI Cancer Center Support Grant P30 CA008748. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.