Yan Leyfman, Medical Correspondent at OncLive, Freelance, Co-Founder and Executive Director of MedNews Week, shared on LinkedIn:
“Could a Commonly Prescribed Medication Affect Outcomes After CAR-T Therapy Through Changes in the Gut Microbiome?
Proton pump inhibitors (PPIs) can disrupt gut microbial diversity, including reducing Bifidobacteriaceae, a bacterial family implicated in antitumor immune responses. Given the growing evidence linking the gut microbiome to CAR-T efficacy and toxicity, investigators examined whether PPI exposure before axicabtagene ciloleucel (axi-cel) infusion was associated with clinical outcomes.
In this multicenter retrospective study of 255 patients with relapsed or refractory B-cell lymphoma, PPI exposure within 28 days before infusion was associated with a higher incidence of ICANS:
- ICANS: 66% with PPI exposure vs 49% without (p=0.016)
- CRS: 88% vs 85%, with no significant difference
- Complete response at 3 months: 53% vs 66% (p=0.20)
- Progression-free survival: 379 vs 372 days (HR 0.99; p=0.94)
- Overall survival: no significant difference
The association with ICANS persisted in the overall analysis, although it was not clearly dose-dependent and lost significance in dose-stratified analyses. Importantly, PPI exposure did not appear to compromise response, relapse outcomes, or survival.
These findings raise an interesting question about how concomitant medications and microbiome modulation may influence immune effector cell toxicity. However, the retrospective design, potential confounding, and lack of documented PPI indications prevent conclusions about causality.
The practical takeaway is not to routinely discontinue PPIs, but to reassess their indication before CAR-T when clinically appropriate.
Medication optimization may be another component of supportive care as we continue to refine CAR-T safety.”
Title: Proton pump inhibitors and outcome after axicabtagene ciloleucel for the treatment of non-Hodgkin B-cell lymphoma, a retrospective study with the DESCAR-T registry
Authors: Eva Desbrousses, Roch Houot, Thierry Lamy de La Chapelle, Benoit Tessoulin, Thomas Gastinne, Stéphanie Guidez, Niels Moya, Aline Tanguy-Schmidt, Jérôme Paillassa, Vivien Dupont, Elodie Gat, Martin Eloit, Emmanuel Gyan, Nicolas Vallet.
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