TY - JOUR
T1 - Itacitinib for prevention of graft-versus-host disease and cytokine release syndrome in haploidentical transplantation
AU - Abboud, Ramzi
AU - Schroeder, Mark A.
AU - Rettig, Michael P.
AU - Jayasinghe, Reyka G.
AU - Gao, Feng
AU - Eisele, Jeremy
AU - Gehrs, Leah
AU - Ritchey, Julie
AU - Choi, Jaebok
AU - Abboud, Camille N.
AU - Pusic, Iskra
AU - Jacoby, Meagan
AU - Westervelt, Peter
AU - Christopher, Matthew
AU - Cashen, Amanda
AU - Ghobadi, Armin
AU - Stockerl-Goldstein, Keith
AU - Uy, Geoffrey L.
AU - DiPersio, John F.
N1 - Publisher Copyright:
© 2024 American Society of Hematology
PY - 2024
Y1 - 2024
N2 - Haploidentical hematopoietic cell transplantation (haplo-HCT) is an increasingly used treatment for hematologic malignancies. Although posttransplant cyclophosphamide (PtCy) has improved graft-versus-host disease (GVHD) prophylaxis in haplo-HCT, patients continue to experience life-threatening complications. Interferon gamma and interleukin-6 are central in the pathophysiology of GVHD and cytokine release syndrome (CRS), and both cytokines signal through Janus kinase 1 (JAK-1). We tested the effect of adding the JAK-1 selective inhibitor, itacitinib, to PtCy–haplo-HCT to mitigate these complications and improve overall survival (OS). This open-label, single-arm study evaluated the safety and efficacy of itacitinib combined with standard GVHD prophylaxis after haplo-HCT. A total of 42 patients were treated with itacitinib 200 mg daily from day −3 through +100 or +180, followed by a taper. Itacitinib resulted in low CRS grades, all patients had grade 0 (22%) or grade 1 (78%) CRS and there were no cases of grade 2 to 5 CRS. There were no cases of primary graft failure. No patients developed grade 3 to 4 acute GVHD (aGVHD) through day +180. The cumulative incidence of grade 2 aGVHD at day +100 was 21.9%. The 1-year cumulative incidence of moderate or severe chronic GVHD was 5%. The cumulative incidence of relapse at 2 years was 14%. OS at 1 year was 80%. The cumulative incidence of nonrelapse mortality (NRM) at day 180 was 8%. Itacitinib, when added to standard GVHD prophylaxis, was well tolerated and resulted in low rates of CRS, acute and chronic GVHD, and NRM, and encouraging rates of GVHD-free relapse-free survival and OS after haplo-HCT. This trial was registered at www.ClinicalTrials.gov as #NCT03755414.
AB - Haploidentical hematopoietic cell transplantation (haplo-HCT) is an increasingly used treatment for hematologic malignancies. Although posttransplant cyclophosphamide (PtCy) has improved graft-versus-host disease (GVHD) prophylaxis in haplo-HCT, patients continue to experience life-threatening complications. Interferon gamma and interleukin-6 are central in the pathophysiology of GVHD and cytokine release syndrome (CRS), and both cytokines signal through Janus kinase 1 (JAK-1). We tested the effect of adding the JAK-1 selective inhibitor, itacitinib, to PtCy–haplo-HCT to mitigate these complications and improve overall survival (OS). This open-label, single-arm study evaluated the safety and efficacy of itacitinib combined with standard GVHD prophylaxis after haplo-HCT. A total of 42 patients were treated with itacitinib 200 mg daily from day −3 through +100 or +180, followed by a taper. Itacitinib resulted in low CRS grades, all patients had grade 0 (22%) or grade 1 (78%) CRS and there were no cases of grade 2 to 5 CRS. There were no cases of primary graft failure. No patients developed grade 3 to 4 acute GVHD (aGVHD) through day +180. The cumulative incidence of grade 2 aGVHD at day +100 was 21.9%. The 1-year cumulative incidence of moderate or severe chronic GVHD was 5%. The cumulative incidence of relapse at 2 years was 14%. OS at 1 year was 80%. The cumulative incidence of nonrelapse mortality (NRM) at day 180 was 8%. Itacitinib, when added to standard GVHD prophylaxis, was well tolerated and resulted in low rates of CRS, acute and chronic GVHD, and NRM, and encouraging rates of GVHD-free relapse-free survival and OS after haplo-HCT. This trial was registered at www.ClinicalTrials.gov as #NCT03755414.
UR - http://www.scopus.com/inward/record.url?scp=85212412655&partnerID=8YFLogxK
U2 - 10.1182/blood.2024026497
DO - 10.1182/blood.2024026497
M3 - Article
C2 - 39576962
AN - SCOPUS:85212412655
SN - 0006-4971
JO - Blood
JF - Blood
ER -