Panobinostat with standard prophylaxis may reduce incidence of acute graft vs host disease (aGVHD) following stem cell transplant with matched donors, according to research published in Blood Advances.

GVHD remains a challenging complication of allogeneic hematopoietic stem cell transplantation (HCT). Nonselective panhistone deacetylase inhibitors (HDACis) show promise in preventing acute GVHD.

Panobinostat is an HDACi approved to treat relapsed and relapsed/refractory multiple myeloma. In this phase 2 prospective trial, the authors tested PANO plus tacrolimus and sirolimus to reduce aGVHD.

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Patients received varying conditioning regimens, but all received panobinostat on day -5 or -6, tacrolimus on day -3, and sirolimus on day -1. Panobinostat was used for 6 months to provide extended benefit and minimize relapse after HCT.

A total of 38 participants were evaluated for the primary endpoint. Patients had acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), acute lymphoblastic leukemia (ALL), or another hematologic malignancy. 

All patients underwent HCT with a matched sibling or matched unrelated donor. A total of 9 patients (23%) completed 26 weeks of uninterrupted treatment with panobinostat.

At day 100, the cumulative incidence of aGVHD grade II to IV was 18.4% (7 patients), and the cumulative incidence of any grade aGVHD was 31.6%. The authors noted that this incidence is lower than previously reported rates in other studies that used a standard immune prophylaxis.

The 12-month overall survival (OS) was 89.5%, with a relapse-free survival of 78.9% and a GVHD relapse-free survival of 60.5%. The 36-month OS was 69.7% and relapse-free survival was 72.1%.

The most common adverse events related to panobinostat were thrombocytopenia, leukopenia, gastrointestinal toxicity, rash, renal failure/peripheral edema, and periorbital edema. All of these events were expected and consistent with previous studies.

Overall, panobinostat with tacrolimus and sirolimus is tolerable and improved incidence of aGVHD for patients undergoing matched HCT. Further testing is still needed with larger trial populations.

Disclosure: A study author declared affiliations with biotech, pharmaceutical and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Perez L, Fernandez H, Kharfan-Dabaja M, et al. A phase 2 trial of the histone deacetylase inhibitor panobinostat for graft-versus-host disease prevention. Blood Adv. 2021;5(13):2740-2750. doi:10.1182/bloodadvances.2021004225