Loading ...

TOPLINE:

Prophylactic itacitinib twice daily significantly reduced the incidence of grade ≥ 2 cytokine release syndrome (CRS) compared with placebo (17.4% vs 56.5%) in patients receiving immune effector cell therapy. The JAK1 inhibitor also demonstrated a favorable safety profile without impacting treatment efficacy.

METHODOLOGY:

• A total of 111 patients were enrolled across 10 US study sites in this two-part phase 2 trial, with 63 patients in part 1 and 48 patients in part 2.
• Part 1 participants received 200 mg itacitinib once daily for 3 days before immune effector cell infusion through day 26, while part 2 participants were randomized 1:1 to receive either 200 mg itacitinib twice daily or placebo.
• The primary endpoint measured the proportion of patients with grade ≥ 2 CRS by day 14 using the American Society for Transplantation and Cellular Therapy consensus grading system.
• Secondary endpoints included incidence of any grade or grade ≥ 2 CRS by day 28, incidence and severity of immune effector cell-associated neurotoxicity syndrome (ICANS) by day 28, time to onset and duration of CRS and ICANS, therapeutic intervention requirements, and safety.

TAKEAWAY:

• Prophylactic administration of 200 mg itacitinib twice daily significantly reduced grade ≥ 2 CRS incidence by day 14 compared with placebo (17.4% vs 56.5%; P = .003).
• Grade ≥ 2 ICANS occurred in fewer patients receiving itacitinib twice daily compared with those receiving placebo (8.7% vs 21.7%).
• Best overall response rate was comparable between itacitinib twice daily and placebo groups (78.3% vs 73.9%), with complete metabolic response rates of 60.9% and 47.8%, respectively.
• Molecular analysis revealed significant reductions in TNF-alpha, interleukin 6, and interleukin 2 receptor A levels in patients receiving itacitinib compared to placebo.

IN PRACTICE:

“Taken together, these data suggest that prophylaxis with 200 mg itacitinib twice daily is generally well tolerated and shows promising activity for reducing the incidence and severity of CRS and ICANS following IEC [immune effector cell] therapy, which may potentially shift the standard of care for these patients,” the authors of the study wrote.

SOURCE:

This study was led by Matthew J. Frigault, MD, Hematopoietic Cell Transplant and Cell Therapy Program, Cancer Center, Massachusetts General Hospital in Boston. It was published online in Blood.

LIMITATIONS:

According to the authors, most findings were derived from patients with diffuse large B-cell lymphoma as the underlying hematologic malignancy. Further studies with larger sample sizes are needed to determine if the effects of itacitinib are consistent for other indications.

DISCLOSURES:

This study was funded by Incyte Corporation. Frigault disclosed having ties with Arcellx, Bristol Myers Squibb, Editas, Iovance, Kite, and Novartis. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.