Itacitinib for the prevention of IEC therapy–associated CRS: results from the 2-part phase 2 INCB 39110-211 study Journal Article
| Authors: | Frigault, M. J.; Maziarz, R. T.; Park, J. H.; Lazaryan, A.; Shah, N. N.; Svoboda, J.; Lekakis, L.; Reshef, R.; Phillips, C. L.; Burke, L.; Lei, J.; Pratta, M.; Morariu-Zamfir, R.; DiPersio, J. F. |
| Article Title: | Itacitinib for the prevention of IEC therapy–associated CRS: results from the 2-part phase 2 INCB 39110-211 study |
| Abstract: | Cytokine release syndrome (CRS) and immune effector cell (IEC)–associated neurotoxicity syndrome (ICANS) are common complications after IEC therapy for hematologic malignancies. This 2-part phase 2 study (INCB 39110-211) investigated the safety and efficacy of itacitinib, a potent, highly selective Janus kinase 1 inhibitor with broad anti-inflammatory activity, for the prevention of CRS and ICANS in patients who received commercial CD19-directed IEC therapy. Patients in part 1 received 200 mg itacitinib once daily 3 days before IEC therapy (axicabtagene ciloleucel [axi-cel], brexucabtagene autoleucel, or tisagenlecleucel) through day 26 with guidelines for use of other CRS/ICANS interventions. In part 2 (double-blind), patients were randomized to receive 200 mg itacitinib twice daily or placebo 3 days before IEC therapy with axi-cel. The primary end point was the proportion of patients with CRS grade ≥2 by day 14 using the American Society for Transplantation and Cellular Therapy consensus grading system. Overall, 111 patients were enrolled (63 in part 1; 48 in part 2); 109 patients were analyzed for efficacy and 110 for safety. By day 14, grade ≥2 CRS occurred in fewer patients on 200 mg twice daily itacitinib (17.4%) than on placebo (56.5%; P = .003). The proportion of patients with grade ≥2 ICANS by day 28 was lower than with placebo (8.7% vs 21.7%). Itacitinib was well tolerated, with pyrexia being the most common treatment-emergent adverse event (200 mg itacitinib twice daily, 43.5%; placebo, 50.0%), and itacitinib-related cytopenias were manageable. Itacitinib did not affect IEC therapy efficacy (objective response rate at 6 months, 39.1% [200 mg itacitinib twice daily] vs 26.1% [placebo]). This study was registered at www.clinicaltrials.gov as #NCT04071366. © 2025 American Society of Hematology |
| Journal Title: | Blood |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Publication status: | Online ahead of print |
| Date Published: | 2025-01-01 |
| Online Publication Date: | 2025-01-01 |
| Language: | English |
| DOI: | 10.1182/blood.2024026586 |
| PUBMED: | 40090005 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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