A Case Report of the Benefit of Cannabidiol (Cannabidiol (CBD)-Predominant Medical Cannabis Preparation) in the Management of Refractory Skin Graft Vshost Disease (GVHD)

Abstract

Cannabis sativa contains numerous cannabinoids, with D9-tetrahydrocannabinol (THC) and cannabidiol (CBD), the primary cannabinoids. Both possess potent anti-inflammatory and immunosuppressive properties, but THC has significant psychoactive properties. Yeshuron's phase 2 study of CBD plus standard GVHD prophylaxis found low rates of grade 2-4 acute(A-) GVHD, and compared with 101 historical controls given standard GVHD prophylaxis, the hazard ratio of developing grades 2-4 A-GVHD was .3 (P =.0002). Kalytera Therapeutics announced a Phase 2a study of CBD for treatment of Grade 3 - 4 A-GVHD, including 9/ 10 responses, of which 7 were complete remission (CR). We report a case of steroid refractory eczematous GVHD successfully treated with a CBD predominant medical cannabis product. A 35 year old woman with T-cell Acute Lymphoblastic Leukemia with CNS involvement in complete remission underwent matched related donor stem cell transplant (SCT) conditioned with Etoposide, TBI 1200 cGy. GvHD prophylaxis was Alemtuzumab, Tacrolimus. A rash developed on day 126 post transplant involving face and scalp and within 1 week involved 100% BSA with itching, facial and orbital swelling, ankle/feet swelling. Skin biopsy revealed an eczematous variant of GvHD known to be very aggressive, difficult to control with immunosuppression , and carries a poor prognosis. Phototherapy and steroid ointment provided initial benefit and regression of rash but it recurred within 6 months. Ruxolitinib provided no benefit. Systemic steroids were restarted at 1mg/kg/ day with minimal benefit. Photopheresis offered only minimal response. Ibrutinib was added. With steroids, photopheresis and ibrutinib she had only marginal response . Numerous infectious complications including soft tissue skin infections required multiple admissions. At 16 months post SCT, she began a medical cannabis product manufactured by VIREO HEALTH, consisting of a high CBD:THC ratio (19:1) oral solution containing CBD 47.5mg/ml and THC 2.5mg/ml. A daily dose of 6 ml provided 285 mg CBD and 15mg THC daily comparable to the 300 mg CBD Kalytera product. Toxicity was sleepiness; thus it was dosed in the evening. There was a definite response within 3 months, allowing discontinuation of ibrutinib and photopheresis. By 2 years post SCT, her GVHD had resolved with only mild itching and flakiness. Her response is sustained 1 year after starting CBD. She remains on 6 ml daily. This adds to the evidence of the anti- inflammatory and immunosuppressive effects of medical cannabis and its activity for the treatment of active GVHD. THC and CBD are anti-inflammatory via CB2 receptors. THC inhibits T-lymphocyte expansion in a murine BMT model. The THC component may have both therapeutic benefit and dose limiting toxicity. Further studies are warranted to explore the role, optimal dose of medical cannabis, in the management of GVHD.