Introduction: Advances in relapse and GVHD prevention have led to improved effectiveness and safety of allogeneic hematopoietic cell transplantation (HCT) over the decades, thus making allogeneic HCT a potentially curative possibility for more patients. Unfortunately, despite improved long-term survival, both relapse and GVHD impact long-term outcomes, and QoL is reduced in HCT recipients (Beer et al., Bone Marrow Transplant, 2025). Given limitations of current treatment and prophylaxis regimens in terms of efficacy, adverse effects, and need for close laboratory monitoring, there is a need for therapies that promote better long-term outcomes after HCT.

We report an updated analysis of long-term outcomes and new QoL data on patients who received novel calcineurin inhibitor-free GVHD prophylaxis with PTCy + aba compared to patients who received methotrexate and tacrolimus (Control) in a prospective randomized controlled clinical trial previously described (Koura et al., Blood Advances, 2025: ID IM101-701; protocol #180383).

Methods: In this institutional review board approved follow-up, original study participants were contacted 2-5 years post-HCT to complete the validated QoL assessment, Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale (FACT-BMT) (McQuellon, Bone Marrow Transplantation, 1997). Additional long-term outcomes data were obtained from electronic medical record review, including overall survival (OS), relapse, chronic (c)GVHD, cGVHD-relapse free survival (cGRFS), and systemic treatment for cGVHD. Fisher's exact test was utilized for categorical endpoint analyses. FACT-BMT QoL scores were analyzed with the independent two-sample T-test. In this analysis, patients who experienced a catastrophic event, including death or relapse, and those who did not complete the FACT-BMT for other reasons were excluded from QoL analysis. P < 0.05 was considered significant for analyses.

Results: 24 patients were randomized to PTCy + aba and 14 to the Control arm and were included in subsequent analyses. Patient characteristics have been previously published. Notably, disease risk was not evenly balanced in the initial trial, with more patients transplanted in complete remission (CR)2 versus CR1 in the PTCy + aba arm [PTCy + aba in CR2 = 8/24 (33%) vs. Control in CR2 = 2/14 (14%)]. At 2-5-year follow-up, there was no difference in cGRFS (p = 0.294) or OS (p = 0.472) between arms. Moderate-severe cGVHD was significantly different, with higher incidence of cGVHD in the Control arm (PTCy + Aba N = 1; Control N = 9; p = 0.0001*). Freedom from relapse was also significantly different, with increased relapse observed in the PTCy + aba arm (PTCy + Aba N = 13; Control N = 2; p = 0.02*). Of the patients who relapsed in the PTCy + aba arm, the majority went on to receive subsequent therapy, including 9 who received donor lymphocyte infusion (DLI) and 1 who received CAR-T therapy. Two patients developed moderate-severe cGVHD following DLI.

6 patients in the PTCy + Aba arm completed a FACT-BMT assessment and had not experienced a catastrophic event at long-term follow-up (M = 91.18, SD = 24.71) versus 8 patients in the Control arm (M = 111.3, SD = 14.11). Between arms, there was no difference between FACT-BMT QoL scores, p = 0.078. Additionally, there was no difference in FACT-BMT scores between arms for those achieving cGRFS (PTCy + Aba N = 5, M = 98.62, SD = 18.66; Control N = 3, M = 118, SD = 17.78; p = 0.20). Non-response rates were greater among patients on the PTCy + aba arm who achieved cGRFS (5/11) versus the control arm (0/3). In the PTCy + aba arm 4 patients required systemic cGVHD therapy > 1-year post-HCT versus 11 in the control arm.

Conclusions: This exploratory analysis found the intervention, PTCy + aba GVHD prophylaxis, at 2-5 year long-term follow-up was associated with sustained decreased cGHVD, with no difference in cGRFS and OS compared to the Control arm. There was a trend for more relapses on the PTCy + aba arm. This was confounded by small sample size and the fact that patients were stratified based on GVHD and not relapse risk, resulting in more patients with high-risk disease on the intervention arm.QoL at long-term follow-up was not different between arms, with results also limited by small sample size and confounded by non-response bias. Long-term outcomes, including QoL, are important endpoints to evaluate GVHD prophylaxis regimens and warrant investigation in future prospective studies.

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2025
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