Al-Ola A Abdallah: Clonal Hematopoiesis and Inflammation in BCMA CAR-T Outcomes
Al-Ola A Abdallah, Associate Professor and Plasma Cell Disorder Program Director of the Division of HMCT at the University of Kansas Medical Center, shared a post on X about a paper by Zachary M. Avigan et al. published in Clinical Cancer Research:
“Clonal Hematopoiesis and Inflammation in BCMA CAR-T Outcomes (MM)
CAR-T for MM has transformed outcomes, but prolonged cytopenias and secondary myeloid disease (MDS/AML) remain major concerns.
This single-center study (n=213) highlights how clonal hematopoiesis (CH) + inflammation shape post-CAR-T toxicity and survival.
Prolonged cytopenias = worse survival
- 19% had persistent grade ≥3 cytopenia at day 100.
- Lack of recovery = shorter PFS (15 vs 29 mo) and worse 24-mo OS (55% vs 87%).
- 64% of these had cytopenias lasting >1 year despite remission.
Inflammation + CH predict recovery
- Elevated ferritin ≥300 ng/mL → slower recovery.
- CH in 39% (DNMT3A 18%, TP53 12%).
- CH + high ferritin = markedly delayed myeloid recovery (HR 0.34, p=.0009).
- Distinct pro-inflammatory cytokine profile seen before infusion.
Secondary myeloid disease
- 9% developed MDS/AML, median 14.5 mo post-CAR-T.
- Nearly all are linked to the expansion of TP53-mutated CH clones.
- TP53 VAF is high from 3.4% – 44% in disease.
- Non-TP53 CH mutations remained stable.
Outcomes of secondary myeloid disease
- Median OS after MDS/AML = 7 mo.
- High-risk features common: complex karyotype, monosomy 7/del7q.
- Highlights CAR-T’s potential role in accelerating TP53-driven clonal evolution.
Translational implications
- Pre-CAR-T screening for CH (esp. TP53) + ferritin may guide risk stratification.
- High-risk patients need closer monitoring for cytopenias and MDS/AML.
- Inflammatory/endothelial signatures = potential therapeutic targets.
Bottom line for clinicians
- Prolonged cytopenias post-CAR-T = poor outcomes.
- TP53 CH + inflammation = red flag for delayed recovery and secondary myeloid disease.
- Careful risk-benefit assessment is essential before CAR-T in these patients.”
Title: Clonal hematopoiesis and inflammation predict hematologic toxicity and secondary myeloid malignancies after BCMA-directed chimeric antigen receptor T cell therapy
Authors: Zachary M. Avigan, Jerrel Catlett, Saoirse Bodnar, Darren Pan, Adolfo Aleman, Tianxiang Sheng, Erin Moshier, Adriana C. Rossi, Shambavi Richard, Gurbakhash Kaur, Joshua Richter, Larysa J. Sanchez, Cesar Rodriguez, Hearn Jay. Cho, Shafinaz Hussein, Christian Salib, Lewis R. Silverman, Sundar Jagannath, Samir Parekh, Santiago Thibaud
You can read the Full Article on Clinical Cancer Research.
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