Association of Cyclosporine Exposure Post-Allogeneic Hematopoietic Cell Transplant with Graft Failure and Relapse Risk in Hematological Malignancies.

Background: Allogeneic hematopoietic cell transplantation (HCT) is a cornerstone in the treatment of many high-risk hematological malignancies. Calcineurin inhibitors (CNIs), essential components of GVHD prophylaxis, require careful monitoring of levels to optimize outcomes. This study evaluated the association between cyclosporine (CsA) exposure during the first 90 days post-HCT and key transplant outcomes.

Methods: A retrospective analysis was performed on 373 patients who underwent allogeneic HCT between January 2019 and July 2021 at the Princess Margaret Cancer Centre. CsA trough levels were routinely measured, and area under the curve for the first 90 days post-transplant (AUC90) was calculated. Associations between CsA AUC90 and graft failure (GF), relapse, acute and chronic GVHD (aGVHD, cGVHD), and infections were assessed.

Results: In a cohort predominantly receiving contemporary GVHD prophylaxis with PTCy-based regimens, higher CsA AUC90 was significantly associated with a reduced risk of GF (p<0.001) and lower grades of aGVHD (p<0.001). Univariable analysis confirmed that higher CsA exposure was linked to a lower risk of GF (HR 0.22, p<0.001). CsA AUC90, however, was not associated with relapse risk (p=0.56) or cGVHD severity (p=0.38). Increased CsA exposure was associated with a higher risk of CMV reactivation (p=0.03), though this risk was mitigated in patients receiving letermovir prophylaxis (p=0.44).

Conclusion: This study underscores the importance of CsA monitoring to reduce the risks of GF and aGVHD without increasing relapse in hematological malignancies. However, higher CsA exposure requires careful management due to its association with CMV reactivation. These findings contribute to optimizing immunosuppression strategies in the context of contemporary GVHD prophylaxis.