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. 2023 Jul 25;7(14):3604-3611.
doi: 10.1182/bloodadvances.2023010545.

PTCy, abatacept, and a short course of tacrolimus for GVHD prevention after haploidentical transplantation

A Samer Al-Homsi  1 , Frank Cirrone  1 , Stephanie Wo  1 , Kelli Cole  1 , J Andres Suarez-Londono  1 , Sharon L Gardner  1 , Jingmei Hsu  1 , Kelsey Stocker  1 , Benedetto Bruno  2 , Judith D Goldberg  3 , Benjamin A Levinson  3 , Maher Abdul-Hay  1
Affiliations

PTCy, abatacept, and a short course of tacrolimus for GVHD prevention after haploidentical transplantation

A Samer Al-Homsi et al. Blood Adv. .

Abstract

Reducing the incidence of graft-versus-host disease (GVHD) after haploidentical hematopoietic stem cell transplantation (HSCT) is warranted. Posttransplant cyclophosphamide (PTCy) is the main agent used for GVHD prevention in this setting. It remains unknown whether costimulation blockade can be safely combined with PTCy and enhance its efficacy. We performed a phase 1b-2 clinical trial to examine the combination of PTCy, abatacept, and a short course of tacrolimus (CAST) after peripheral blood haploidentical HSCT. The primary end point was the incidence of grades 2-4 acute GVHD by day +120. The study enrolled 46 patients with a median age of 60 years (range, 18-74 years). The cumulative incidences of grades 2-4 and 3 or 4 acute GVHD were 17.4% (95% confidence interval [CI], 9.2-32.9) and 4.4% (95% CI, 1.1-17.1), respectively. With a median follow-up of 15.3 months, the cumulative incidence of 1-year treatment-related mortality was 4.4% (95% CI, 1.1-17.1). The estimated 1-year moderate-to-severe chronic GVHD rate, relapse rate, progression-free survival, overall survival, and GVHD- and relapse-free survival were 15.9% (95% CI, 8-31.7), 11.7% (95% CI, 5-27.2), 84.1% (95% CI, 73.8-95.7), 85.9% (95% CI, 75.9-97.2), and 66.1% (95% CI, 53.4-81.8), respectively. Toxicities were similar to those expected in patients receiving haploidentical HSCT. This clinical trial showed that the CAST regimen is safe and effective in reducing the rate of grades 2-4 acute GVHD after haploidentical peripheral blood HSCT. This trial was registered at www.clinicaltrials.gov as #NCT04503616.

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Conflict of interest statement

Conflict-of-interest disclosure: A.S.A.-H. has received an educational grant from Bristol Myers Squibb and served as scientific advisory board member for Incyte. M.A.-H. has served as consultant for Jazz; a scientific advisory board member for Kite, Daiichi, Rigel, and Incyte; and speaker for Jazz, Takeda, and Servier. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Study scheme.
Figure 2.
Figure 2.
Engraftment. Cumulative incidence of neutrophil engraftment on day +30 and platelet engraftment on day +100.
Figure 3.
Figure 3.
Cumulative incidence of acute and chronic GVHD. Cumulative incidence of GVHD with death as a competing risk. (A) Acute GVHD grade 2-4 and (B) chronic GVHD, moderate-to-severe.
Figure 4.
Figure 4.
Outcomes. (A) One-year cumulative incidence of relapse. (B) Kaplan-Meier survival curves.
Figure 5.
Figure 5.
Immune reconstitution. Violin plot constructed using https://www.bioinformatics.com.cn/en.
See this image and copyright information in PMC

References

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