Abstract A041: Prognostic significance of post-CAR-T macrocytosis in large B-cell lymphoma
Shady I. Tantawy, Mark Hamilton, Dai Chihara, Luis E. Fayad, Chijioke Nze, Ranjit Nair, Swaminathan Iyer, Hun Lee, Luis Malpica, Ayushi Chauhan, Fateeha Furqan, Anath Lionel, Ryan Sun, Iman Sarami, Danielle Hammond, Partow Kebriaei, Elizabeth Shpall, Jason Westin, Christopher Flowers, Sairah Ahmed, Paolo Strati, Sattva NeelapuAbstract
Background:
New onset red blood cell macrocytosis is frequently observed in patients (pts) with large B-cell lymphoma (LBCL) treated with CAR T-cell therapy. We aimed to describe the incidence and temporal trends in mean corpuscular volume (MCV) following CAR-T therapy and evaluate its prognostic significance.
Methods:
We retrospectively analyzed all LBCL pts who received standard-of-care CAR-T therapy between January 2020 and December 2024 and had at least one year of follow-up. Baseline characteristics, longitudinal changes in MCV, incidence of prolonged cytopenias and myeloid disorders, severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), response rates, and progression-free survival (PFS) and overall survival (OS) were compared between pts with and without post–CAR-T macrocytosis. Presence of myeloid disorders was assessed by bone marrow evaluation with or without a customized 81-myeloid gene NGS panel.
Results:
A total of 379 pts with LBCL treated with axi-cel (N=302), liso-cel (N=59), or tisa-cel (N=18) were included. Median MCV increased over time, peaking at 3 months post–CAR-T (median 97 fL, range 76–120) compared to baseline (median 91 fL, range 72–116; p<0.0001), and gradually decreased thereafter. Macrocytosis (MCV >99 fL) developed in 184 pts (48.5%) at a median of 2 months post-CAR-T. It was not associated with baseline characteristics, including age, sex, race, stage, number of prior lines of therapy, or CAR-T product type. Macrocytosis was significantly associated with grade ≥2 anemia (Hb <10 g/dL) and grade 3–4 thrombocytopenia (platelets <50 ×109/L) within 1–6 months post–CAR-T (p=0.0001), but not with neutropenia. At 12 months, macrocytosis remained associated with persistent grade ≥2 anemia compared to pts with normal MCV (p=0.0001). Macrocytosis was not associated with differences in CRS or ICANS severity. Overall and complete response rates, and median PFS (21 vs 20 months) and OS (26 vs 19 months) were not significantly different between the two groups. Myeloid disorders were identified in 20 of 78 (25.6%) pts who underwent post-CAR-T bone marrow evaluation compared with 2 of 126 (1.6%) pts pre-CAR-T. Among those evaluated post-CAR-T, myeloid disorders were more frequent in pts with macrocytosis (32.8%, 19/58) than in those with normal MCV (5%, 1/20; p=0.02). Diagnoses included myelodysplastic syndrome (MDS; n=7, 9%), CHIP/CCUS (n=7, 9%), acute myeloid leukemia (AML; n=4, 5%), chronic myeloid leukemia (CML; n=1, 1.3%), and MDS/MPN overlap (n=1, 1.3%).
Conclusions:
Macrocytosis is common following CAR-T therapy in LBCL and is associated with more severe anemia and thrombocytopenia early after therapy and a higher incidence of myeloid disorders, but not with survival outcomes or treatment-related toxicities. These findings support close monitoring and consideration of bone marrow evaluation in pts who develop macrocytosis after CAR-T. Further studies are needed to elucidate the underlying mechanisms and pathophysiology.
Citation Format:
Shady I. Tantawy, Mark Hamilton, Dai Chihara, Luis E. Fayad, Chijioke Nze, Ranjit Nair, Swaminathan Iyer, Hun Lee, Luis Malpica, Ayushi Chauhan, Fateeha Furqan, Anath Lionel, Ryan Sun, Iman Sarami, Danielle Hammond, Partow Kebriaei, Elizabeth Shpall, Jason Westin, Christopher Flowers, Sairah Ahmed, Paolo Strati, Sattva Neelapu. Prognostic significance of post-CAR-T macrocytosis in large B-cell lymphoma [abstract]. In: Proceedings of the Fifth AACR International Meeting on Advances in Malignant Lymphoma: From Discovery to Clinical Impact; 2026 Jun 24-27; Philadelphia, PA. Philadelphia (PA): AACR; Blood Cancer Discov 2026;7(3_Suppl):Abstract nr A041.