Golidocitinib, a selective JAK1 kinase inhibitor, in treatment of late thrombocytopenia after CAR-T cell therapy: Case report

Abstract BackgroundDespite its remarkable success, CAR-T therapy is accompanied by common adverse events, including cytokine release syndrome (CRS), neurotoxicity (ICANS), and hematologic toxicity. Acute adverse events are now well-recognized, but little information is available on late toxicities, especially the hematologic toxicities represented by thrombocytopenia. A recent study (NCT06408324) enrolled 85 patients with prolonged thrombocytopenia induced by CAR-T and found that, thrombopoietin receptor agonists (TPO-RAs) did not increase the rate of thrombocytopenia resolution relative to supportive care (https://pubmed.ncbi.nlm.nih.gov/39880098/). Here, we reported two cases of successfully treated late thrombocytopenia in relapsed/refractory (R/R) lymphoma with golidocitinib, a highly selective kinase inhibitor of JAK1. Potential mechanisms were explored by single-cell RNA sequencing (scRNA-seq) of residual CAR-T cells during golidocitinib treatment.Case PresentationsCase 1A 69-year-old man was diagnosed with grade 3, stage IVB high-risk follicular lymphoma in 2020. From 2020 to 2024, he received multiple lines of treatment, including R-DHAP, R-GemOx, and RB-CHOP, but none achieved a durable remission. The patient pinned his hope on CAR-T cell therapy, and received CD19-directed CAR-T therapy (dosage=3 × 106/kg) in January 2025. The patient achieved partial remission (PR) and grade 2 CRS was the only acute adverse event noted. Five months after CAR-T infusion, the patient was assessed as disease progression and received radiotherapy. On day 17 after radiotherapy, the platelet count was decreased to 15 ×10⁹/L. Given his history of CAR-T therapy and persistent thrombocytopenia, quantitative CAR transgene testing was performed, showing increased CAR-T activity (from 70 on the day radiotherapy started to 280 copies/ug PBMC DNA). The patient was subsequently treated with romiplostim (250 μg, once weekly) for 2 weeks, but this did not lead to a significant improvement in platelet counts. One month after the onset of thrombocytopenia, golidocitinib was administered orally at a dose of 150 mg once daily, resulting in a gradual recovery of platelet levels. On day 7 of golidocitinib treatment, the patient's platelet count increased to 68 × 10⁹/L. Through scRNA-seq, we found golidocitinib could halt the secretion of Granzyme K (GZMK) from residual CAR-T cells.Case 2A 57-year-old man was diagnosed with Epstein-Barr virus (EBV)-positive angioimmunoblastic T-cell lymphoma (AITL) in 2017. Despite receiving 15 lines of therapy over the subsequent seven years—including chemotherapy, immunotherapy, epigenetic agents, radiotherapy, and targeted therapies—he failed to achieve a durable remission. A re-biopsy in December of 2024 revealed the transformation from AITL to EBV-positive diffuse large B-cell lymphoma (DLBCL). The patient elected to undergo CAR-T therapy. In April 2025, he received an infusion of 2 × 106/kg autologous T cells (1.2 × 108 in total) engineered to express a CAR targeting CD19. On day 16 post-infusion, he developed neurological symptoms, including resting tremor and gait instability. Acute adverse events included grade 1 ICANS and grade 2 CRS. The patient responded to corticosteroids, anti-IL-6 therapy, and antimicrobial agents. On day 40 after CAR-T therapy, a complete metabolic response (CMR) was confirmed by PET-CT. However, thrombocytopenia developed three months after CAR-T cell infusion. Eltrombopag (2.5 mg orally, once daily) was administered for 2 weeks to manage thrombocytopenia. Unfortunately, severe thrombocytopenia persisted, with a platelet count of 19 × 10⁹/L at the end. As there was no response to eltrombopag, golidocitinib (150 mg orally, once daily) was initiated on July 16. On day 8 of golidocitinib treatment, the patient's platelet count increased to 47 × 10⁹/L. Through scRNA-seq, we also found the proportion of GZMK+ CAR-T cells was decreased significantly during golidocitinib treatment.ConclusionsThe biology of late thrombocytopenia following CAR-T therapy is unique, including the specific GZMK+phenotype of residual CAR-T cells. Golidocitinib, a highly selective JAK1 inhibitor, has shown promising activity in treating this adverse event. However, more clinical cases and further studies are needed to confirm this hypothesis.