Previous research offers some fairly strong evidence that cannabis use has the potential to suppress immune system functioning (Eur J Immunol 2010;40:3358-3371). That could be a problem if the increasingly commonly used drug is being taken by cancer patients on immunotherapies. And that's why Gil Bar-Sela, MD, Head of Supportive and Palliative Care at Rambam Health Care Campus in Haifa, Israel, and his colleagues decided to investigate potential interactions between cannabis and the immunotherapy nivolumab. They presented their data at the ESMO 2017 Congress in Madrid in September (Abstract 1545PD).
The researchers led a retrospective, observational study that analyzed records of 140 patients treated with nivolumab at Rambam Health Care Campus between 2015 and 2016. Eighty-nine patients reported only taking the cancer drug, and 51 patients reported taking the cancer drug, as well as using cannabis. The patients in the trial were taking nivolumab to treat either advanced melanoma, non-small cell lung cancer, or renal clear cell carcinoma.
The analysis showed that cannabis use was the only significant factor that reduced the patients' response to nivolumab for the group: 37.5 percent of the patients not using cannabis had a response to the drug, while 15.9 percent of the patients having reported using cannabis had a response to taking nivolumab. Though, cannabis use did not significantly affect progression-free survival or overall survival among the patients.
Bar-Sela said the results, while not conclusive, are noteworthy for patients taking immunotherapies-and warrant further prospective clinical study.
1 What were the key findings from this research-and which, if any, of the findings were surprising?
"The key finding was the lower response rate to immunotherapy in the group of patients that had taken cannabis [at] the same time. The only parameter that influenced the response rate to immunotherapy was cannabis. Other parameters [including smoking, hypertension, brain metastases, and more] influenced survival and that was not surprising.
"In retrospective data, we collect all available data from the files and run them in the multivariate regression model. Of course, not all of [the results] have meaning. For example, smoking is higher in the lung cancer patients, resulting in lower progression-free survival compared [to patients with] renal cell carcinoma, and so on. These other parameters are related directly to the patients' illnesses and general situations.
"This topic [has not been] reported before. It is the first time. However, some concern was raised in the '90s when some patients with AIDS took cannabis for symptom relief.
"The finding [supports] the hypothesis that such interaction is possible. Cannabis depressed the immune response, according to several basic [studies]."
2 How conclusive were these findings and what implications do these findings have for how cannabis use might affect the effectiveness of other immunotherapies besides nivolumab?
"The data is retrospective, and results should be taken with caution. [Currently], we are prospectively collecting blood samples from patients undergoing immunotherapy [who are either cannabis users or not] to better understand the specific influence on the immune system.
"The prospective trial is collecting data from all patients using immunotherapy drugs, [either] as single medications or in combination. The main difficulty of such a study is the heterogeneous population of the study and the unknown differences in the immune system we are looking for. So, [this research] probably will serve as a search for differences that will lead to proper laboratory study of the interaction.
"An interaction [with cannabis] is possible for all immunotherapy drugs and is not specific to nivolumab. As far as I know, there is no negative interaction with chemotherapy."
3 What should all practicing oncologists and cancer care providers know about your research and how cannabis use among their patients might be affecting treatments?
"According to basic studies, cannabis probably is immunosuppressed-and in this one study of retrospective data, there was a negative interaction with immunotherapy drugs. Personally, I give this information for patients who are on cannabis and starting immunotherapy or vise versa. I think it is important information for the patients to make the right decisions regarding their treatment.
"This information should be studied more. However, I think it is important for the patients now, not just in a year or two when the data from the prospective trial will be available."