Session: 722. Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution: Poster II
Hematology Disease Topics & Pathways:
Clinical Practice (Health Services and Quality), Diversity, Equity, and Inclusion (DEI) , Therapies
Methods: We enrolled 46 adult patients with hematological malignancies receiving haploidentical transplantation from a relative in a prospective single center pilot phase Ib-II clinical trial. Patients received non-myeloablative, reduced-intensity or myeloablative preparative regimens followed by G-CSF mobilized peripheral blood transplants and a combination of PTCy (50mg/kg on days +3 and +4), Aba (10mg/kg on days +5, +14 and +28) and Tac at a dose adjusted based on blood level. Tac taper was initiated on day +60 and completed by day +90. After treating 30 patients, the study was amended to administer an additional dose of Aba on day +56 based on the noted timing of acute GvHD development and Aba terminal ½ life. Patients received standard supportive care by institutional practice including G-CSF and anti-microbial prophylaxis. Serologically CMV positive patients also received letermovir prophylaxis.
Results: Patient characteristics are summarized in table 1. Importantly, 19 out of 46 (41.3%) patients were from racial or ethnic minorities. The data cutoff date was July 29th, 2022. Three patients were excluded from this analysis due to short follow-up. For the remaining patients, median follow-up was 8.9 months. Median time to neutrophil engraftment was 18 days (13-30). One patient died before achieving platelet (plt) engraftment and 2 patients have not yet achieved plt engraftment. For the remaining 40 patients, median time to plt engraftment was 29 days (16-52). All patients achieved full donor chimerism at the time of count recovery. Tac was successfully tapered off as planned in all but 5 patients. Cumulative incidence of acute GvHD grades II-IV, III-IV and IV with death as competing event was 12.8%, 5.1% and 0%, respectively. One-year (y) cumulative incidence of moderate to severe chronic GvHD was 17.1%. All cases of acute GvHD except 1 grade II acute GvHD were observed in the first 30 patients. Cases of chronic GvHD included 2 cases of overlap syndrome. There was no case of steroid-refractory acute GvHD or GvHD-related death. One-y cumulative incidence of relapse (non-relapse mortality as competing event) was 8.3% (95% CI 0%-17.1%). KM estimates of 1-year relapse-free survival (RFS), overall survival (OS) and GRFS (composite end point of grade III-IV acute GvHD-, chronic GvHD requiring systemic therapy- and relapse-free survival) were 91.7% (95% CI 83%-100%), 90.6% (95% CI 80.9%-100%) and 71.8% (95% CI 57.2%-90%), respectively. None of the safety stopping rules was triggered. There was 1 case of thrombotic microangiopathy due to Tac and 2 cases of sinusoidal occlusive disease, 1 requiring treatment with defibrotide; all 3 patients recovered. There were 2 cases of respiratory failure of undetermined etiology. One-y cumulative incidence of non-relapse mortality (relapse as competing event) was 2.6% (95% CI 0%-7.8%). The incidence of CMV and EBV reactivation was 39.5% and 2.3%, respectively. There was no case of adenovirus or HHV-6 virus reactivation. BK viruria occurred in 27.9% of patients with limited symptomatology (1 patient required treatment with cidofovir). Immune reconstitution results are summarized in figure 1.
Conclusion: CAST is a new GvHD prevention regimen that seems safe and effective, yielding excellent outcomes. CAST also allows early discontinuation of Tac. Outcomes with longer follow-up will be presented at the meeting. If the results are confirmed, CAST might be a step forward toward closing an important health disparity gap in BMT, equalizing the outcomes of haploidentical transplantation and MUD transplants.
Disclosures: Al-Homsi: BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees. Abdul-Hay: Jazz: Consultancy, Speakers Bureau; Servier: Speakers Bureau; Takeda: Speakers Bureau.
OffLabel Disclosure: Cyclophosphamide for GvHD prevention Abatacept for GvHD prevention in haploidentical transplantation Tacrolimus for GvHD prevention
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