INTRODUCTION

Chimeric antigen receptor T-cell (CAR-T) therapy has

transformed outcomes for relapsed/refractory B-cell

malignancies. Among hematologic toxicities,

thrombocytopenia is common after CAR-T and may be

prolonged, creating clinically important risks such as bleeding

and delays to subsequent therapies or trial enrolment

AIM

To systematically review prospective

clinical trial data on the incidence,

severity, duration, risk factors, and

management of thrombocytopenia

after FDA-approved CAR-T therapies.

METHOD

We searched PubMed, Embase, and the Cochrane Library for prospective

interventional clinical trials of axicabtagene ciloleucel, tisagenlecleucel, and

lisocabtagene maraleucel published between January 2016 and January 2026.

We identified 790 records. After removal of 210 duplicates, 580 unique records

were screened by title and abstract, 520 were excluded (preclinical studies, non

FDA approved therapies, case reports, reviews, non-CAR-T immunotherapies,

pediatric-only cohorts, or clearly irrelevant outcomes). 60 full-text articles were

assessed for eligibility, 51 were excluded for reasons including non-prospective

design, absence of thrombocytopenia outcomes, or being reviews/editorials.

Nine prospective interventional trials met inclusion criteria and were included in

the qualitative synthesis.

RESULTS

Across nine pivotal CAR-T trials (ZUMA-1, JULIET,

TRANSCEND NHL-001, ZUMA-7, ZUMA-5, ELARA,

TRANSCEND CLL-004, ZUMA-2, BELINDA), a total

of 1,254 patients were infused. Thrombocytopenia

incidence varied widely: ZUMA-1: 38/101 (38% grade

≥3, 7% persistent at 3 months); JULIET: ~46/115 (40%

any-grade, ~35/115 [30%] grade ≥3); TRANSCEND

NHL-001: 85/270 (31% any-grade), 73/270 (27% grade

≥3), 81/270 (30%) prolonged at day 29; ZUMA-7: 51/170

(30% any-grade), 34/170 (20% grade ≥3); ZUMA-5:

37/148 (25% any-grade), 27/148 (18% grade ≥3);

ELARA: 5/97 (5% any-grade and grade ≥3); TRANSCEND

CLL-004: 59/117 (50% any-grade), 35/117 (30% grade

≥3), with 27/37 recovering by day 90; ZUMA-2: 18/74

(25% any-grade), 12/74 (16% grade ≥3); BELINDA:

53/162 (33% any-grade), 41/162 (25% grade

≥3). Overall, thrombocytopenia ranged from 5%

(ELARA) to 50% (CLL-004), with grade ≥3 events in 16–

38% of patients, highlighting its frequency and clinical

relevance across CAR-T therapies.

CONCLUSIONS

Prospective trial data confirm that thrombocytopenia is a

common and sometimes prolonged toxicity after CAR-T

therapy. Standardized cytopenia reporting and

prospective evaluation of mitigation strategies (including

TPO-RAs and hematopoietic support) are needed.