NEWS

Anti-PD-1, Anti-PD-L1 Drugs Rarely Associated with Serious Immune-Related Adverse Events

March 28, 2018

By Will Boggs MD

NEW YORK (Reuters Health) - The checkpoint inhibitors anti-PD-1 and anti-PD-L1 are rarely associated with serious organ-specific immune-related adverse events, according to a new systematic review and meta-analysis.

"There are obvious serious things like pneumonitis to which people are likely alerted already, and endocrine problems are important to look out for as well,” Dr. Deborah Korenstein from Memorial Sloan Kettering Cancer Center, in New York, told Reuters Health by email. “Beyond the serious problems, we found that non-specific symptoms were just as likely as with control therapies (mostly chemotherapy), which may surprise some clinicians, and will need to be managed in these patients.”

By boosting the body's natural defense against cancer, anti-PD-1 and anti-PD-L1 can generate adverse immune effects on normal tissue, though they appear to be less toxic overall than standard chemotherapy.

Dr. Korenstein and colleagues evaluated the rates of serious organ-specific immune-related adverse events, general adverse events related to immune activation and adverse events consistent with musculoskeletal problems for anti-PD-1 drugs overall and compared with other treatments in their quantitative synthesis and meta-analysis of 13 studies.

Organ-specific immune-related adverse events included hypothyroidism in 5.6% of patients, pneumonitis in 2.2%, colitis in 0.7%, hepatitis in 0.2% and hypophysitis in 0.3%.

Serious events included pneumonitis in 1.4%, colitis in 0.5%, hypothyroidism in 0.2%, hepatitis in 0.1% and hypophysitis in 0.2%, the researchers report in The BMJ, online March 14.

Compared with patients treated in control arms, those treated with anti-PD-1 drugs were 2.88-fold more likely to develop colitis, 5.37-fold more likely to develop pneumonitis, 6.92-fold more likely to develop hypothyroidism and 3.38-fold more likely to develop hypophysitis. These results were all statistically significant.

Patients treated with anti-PD-1 drugs were also more likely than controls to experience rash, fatigue and diarrhea.

Musculoskeletal problems ranged in frequency from 10% to 26% for arthralgia, 6% to 22% for back pain, 6% to 14% for musculoskeletal pain and 2% to 12% for myalgia - rates that were similar to those among controls.

“For clinicians our study points out the breadth of potential toxicities from activating the immune system, which I think is somewhat humbling,” Dr. Korenstein said. “In terms of the big picture, our study emphasizes the fact that drug toxicities emerge over time in general when new drugs are introduced and are important to consider even for life-saving drugs in order to optimally manage patients.”

“There is still tremendous uncertainty regarding longer-term adverse events from immunotherapy,” she concluded. “It’s important for the research community to focus on clarifying what happens longer term, though it will likely take a while for that evidence to emerge. In the meantime, clinicians need to be aware of the large knowledge gap.”

The study had no commercial funding, and the researchers reported no conflicts of interest.

SOURCE: https://bit.ly/2pN6PrF

BMJ 2018.

(c) Copyright Thomson Reuters 2018. Click For Restrictions - http://about.reuters.com/fulllegal.asp


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