Cannabis Used With ICIs Appears to Have No Impact on NSCLC Outcomes

The use of medical cannabis does not appear to impair the efficacy of immune checkpoint inhibitors (ICIs) in people with non-small cell lung cancer, according to a new report.

The findings, based on a mouse model and a cohort of human subjects, could help pave the way for more patients to utilize cannabis to ease pain and improve appetite in jurisdictions where medical cannabis is legal. The study was published in the European Journal of Cancer.

Ido Wolf, MD, of the Tel Aviv Medical Center, in Israel, and colleagues, explained that cannabis has quickly become a key part of palliative care for many people with cancer. In Israel, more than 10,000 people with cancer have been granted licenses to use medical cannabis.

“Hence, medical cannabis has become the most prescribed medication for cancer patients and is prescribed for a wide array of symptoms,” the authors said.

Yet, the growth of medical cannabis remains controversial, in part because of concerns that it might negatively impact the efficacy of other treatments.

Wolf and colleagues noted that cannabinoids, including Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), bind do receptors in the endocannabinoid system, including CB1 and CB2, the latter of which is “most abundantly expressed by immune cell leukocytes.” Thus, they said, cannabis may alter the tumor microenvironment by decreasing pro-inflammatory cytokines and dampening the activation of a patient’s immune response.

That’s of particular concern in patients with NSCLC, because many of those patients rely on ICIs to fight their cancer.

“Tumor response to ICIs relies on the tumor microenvironment and its pro-inflammatory components,” Wolf and colleagues wrote. “Therefore, the use of cannabinoids simultaneously with ICIs might jeopardize its efficacy through the modulation of immune cells expressing CB2 receptors.”

To see whether cannabis affected ICI efficacy, the investigators used a murine model treated with an anti-programmed cell death protein-1 (anti-PD-1) antibody and THC to evaluate their interactions. They found that the use of THC did not negatively affect overall survival in the mice.

Next, they compared outcomes in 201 consecutive patients with NSCLC who received pembrolizumab (Keytruda) as first-line monotherapy with or without cannabis. About half of patients (102) were given licenses for medical cannabis. That group was slightly younger (median age of 68 years, versus 74 years in the non-cannabis group). Females were predominant in the cannabis group (60.8%), unlike the non-cannabis group (34.3% female).

However, the cannabis group was also more likely to have brain metastasis (15.7% versus 5%), and have marginally significant liver metastasis (19.6% versus 10.1%).

Time to progression was 6.1 months in the cannabis-naive group, and 5.6 months in the cannabis group (95% C, 0.82-1.38; P = .386). The cannabis-naive group also had a higher longer survival (OS), though the investigators said the difference did not reach statistical significance, and that the gap was likely due to characteristics of the patient groups.

“The differences in OS can be most likely be attributed to higher disease burden and more symptomatic disease in the cannabis-treated group,” Wolf and colleagues said.

The authors concluded that these data suggest that cannabis does not negatively impact the performance of first-line pembrolizumab monotherapy for patients with NSCLC.

“These data provide reassurance regarding the absence of a deleterious effect of cannabis in this clinical setting,” they wrote.

Reference

Waissengrin B, Leshem Y, Taya M, et al. The use of medical cannabis concomitantly with immune-check point inhibitors (ICI) in Non-Small Cell Lung Cancer (NSCLC): A sigh of relief? European Journal of Cancer. 2022. doi:10.1016/j.ejca.2022.11.022