Cannabidiol for the Prevention of Graft-Versus-Host-Disease after Allogeneic Stem Cell Transplantation: Results of a Phase I/II Study

Purpose: Graft-versus-host-disease (GVHD) affects more than 50% of transplanted patients and is a major obstacle to successful allogeneic stem cell transplantation (alloSCT). Cannabidiol (CBD), a non-psychotropic ingredient of Cannabis has been shown to exhibit potent anti-inflammatory properties in animal models of various autoimmune diseases like multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease and diabetes mellitus. We hypothesized that the addition of CBD to standard GVHD prophylaxis may decrease GVHD incidence and severity.

Patients and methods: We conducted a prospective phase I/II study (NCT01385124). Patients were given oral CBD 300 mg/day from day -7 through day +30 plus standard GVHD immunoprophylaxis consisting of cyclosporine and methotrexate.

Results: Forty-eight consecutive adult patients undergoing alloSCT were enrolled. Thirty-eight patients (79%) had acute leukemia or MDS and 13 patients (27%) had progressive disease. Thirty-five patients (73%) were given a myeloablative conditioning.  The donor was either an HLA identical sibling (n=28), a 10/10 matched unrelated donor (n=16) or a 1-antigen mismatched unrelated donor (n=4). Median follow-up was 16 (range, 7-23) months. There were no grade 3-4 toxicities attributed to CBD. The cumulative incidences of grade 2-4 and grade 3-4 acute GVHD by day 100 were 12% and 5%, respectively. None of the patients developed acute GVHD while consuming CBD. Compared to 101 historical control subjects given standard GVHD prophylaxis, the hazard ratio of developing grade 2-4 acute GVHD among subjects treated with CBD plus standard GVHD prophylaxis was 0.3 (95% CI: 0.2-0.6; p=0.0002). The cumulative incidence of moderate-to-severe chronic GVHD at 1 year was 20%. Relapse rate, non-relapse mortality and overall survival at 1 year were 41%, 11.1% and 68%, respectively.

Conclusions: The combination of CBD with standard GVHD prophylaxis is a safe and promising strategy to reduce the incidence of acute GVHD. A randomized double blind controlled study is warranted.