The effect of cannabis use on tumor response to nivolumab in patients with advanced malignancies

Abstract

Background: In recent years, immunotherapy, which enhances the immune system's response to tumors, has come into clinical use. At the same time, the use of cannabis, which has potential immune-suppressive effects, is increasing in oncology patients, mainly for palliative indications. A large number of patients is being treated with these two modalities and interaction is possible. The aim of this study was to evaluate the influence of cannabis use during immunotherapy treatment on response rate (RR), progression-free survival (PFS) and overall survival (OS). Method(s): In this retrospective, observational study, data was collected from the files of patients treated with Nivolumab in the years 2015-2016 at Rambam Health Care Campus in Haifa, Israel. Nivolumab was given to 140 patients (89 Nivolumab alone, 51 Nivolumab plus cannabis) with advanced melanoma, non-small-cell lung cancer, and renal clear cell carcinoma. The groups were homogenous regarding demographic and disease characteristics. A comparison of patients treated with Nivolumab plus cannabis to Nivolumab alone was made. Result(s): In a multi-variant model, cannabis was the only significant factor which reduced RR to immunotherapy (37.5% RR in Nivolumab alone compared to 15.9% in the Nivolumab plus cannabis group (p=0.016, OR=3.13, CI95% 1.24-8.13). Cannabis use was not a significant factor for PFS or OS. Factors affecting PFS were smoking (adj HR=2.41), brain metastases (adj HR=2.04), and response to therapy (adj HR=4.89). Factors that reduced OS were smoking (adj HR=2.41), brain metastases (adj HR=2.83), hypertension (adj HR=2.28), low performance status and disease progression (adj HR=2.83). Conclusion(s): In this retrospective analysis, the use of cannabis in combination with immunotherapy decreased RR to treatment, without affecting PFS or OS. This information can be critical for a large group of patients, and requires caution when starting immunotherapy. Considering the limitations of the study, further prospective clinical study is needed to investigate possible interaction.