Cannabis May Impact Tumor Response to Immune Checkpoint Inhibitors

Immunotherapy with immune checkpoint inhibitors targeting PD-1 and PD-L1 is now a standard of care for many solid tumors. These agents are highly effective at stimulating anticancer immune responses, resulting in durable responses. Recently, many cancer patients have begun to use medical cannabis as an adjunct to treatment in order to manage disease symptoms, including pain, nausea, vomiting, sleep disturbances, loss of appetite, and mood swings. Cannabis has a known immunomodulatory effect, including suppression of proinflammatory responses, similar to glucocorticosteroids, meaning it has the potential to impact the efficacy of immunotherapy treatment. However, no studies have evaluated the efficacy of PD-1 or PD-L1 inhibitors in patients receiving cannabis.

A retrospective, observational study from a single center in Israel analyzed data from medical charts of 140 patients with advanced melanoma, non-small cell lung cancer (NSCLC), or renal cell carcinoma who were treated with nivolumab. While 89 patients received nivolumab alone, 51 patients also received medical cannabis. Patients who received both nivolumab and cannabis had lower response rates (RR) to nivolumab compared to patients who received nivolumab alone (15.9% vs 37.5%; odds ratio [OR] 3.13, P = .016). The biggest impact was seen in patients with RCC and melanoma, where 40.6% of patients who were not receiving cannabis responded to nivolumab, while only 10.0% of patients receiving cannabis responded to treatment. Among patients with NSCLC, the RR was 24.6% without cannabis and 14.6% with cannabis. The dose, formula, and route of cannabis administration did not impact RR. In multivariate analysis, cannabis use was found to be the only factor affecting the response to treatment. Patients who did not receive cannabis were 3.17 times more likely to respond to immunotherapy.

There were no significant differences in either progression-free survival (PFS; P = .27) or overall survival (OS; P = .045) between patients who received cannabis and those who did not. A multivariate analysis identified smoking, brain metastases, and low performance status as factors significantly impacting PFS and OS. There were no significant differences in adverse events (AEs) between the two groups of patients.

The investigators highlighted that despite the limitations of this small, retrospective study with short follow-up, both physicians and patients should be aware of potential interaction and possible negative impact of cannabis on response to immunotherapy.

Oncologist. 2019 Jan 22. [Epub ahead of print].
cannabis-immunotherapy

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