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Posted by on Jun 28, 2020 in Melanoma | 0 comments

In a nutshell

The study monitored the occurrence of possible immune-related side effects (irSEs) in patients with advanced melanoma under single and combination therapy of ipilimumab (I; Yervoy), nivolumab (N; Opdivo), and pembrolizumab (P; Keytruda). The authors found that combination therapy increases the frequency of irSEs.

Some background

Melanoma is a type of skin cancer. It is currently treated by immunotherapy drugs I, N, and P with success. The drugs work by activating the immune system to find and kill cancer cells. However, they can also negatively affect healthy tissues and organs. As a result, patients face unwanted medical conditions or irSEs. Therefore, patients should be closely monitored and treated with altered therapy. However, the occurrence of irSEs under single or combination therapies of these drugs is unclear for advanced melanoma.

Methods & findings

Results from 35 trials were retrieved from multiple public databases. They involved 6331 patients with advanced melanoma treated by I, N, and P alone (monotherapy) or in different combinations.

Most minor and severe irSEs occurred due to a combination of drugs, compared to monotherapies.

I-N combination caused heart irSEs such as abnormal heart rhythm in 1.1% cases. Whereas, this rate was 0.4% for N alone. The frequency of hormonal irSEs was higher with P-I or N-I combinations. These included abnormal thyroid function and inflammation of the pituitary and thyroid glands.

The frequency of eye disorders was 2.6% with I-P and 2.0% with I-N combinations. Whereas, this rate was less than 1% with monotherapies. A higher risk of low lymphocyte (a type of white blood cells) counts was seen with P and N treatment.

I-N or I-P combinations caused higher frequencies of all or severe digestive tract irSEs, such as – colitis, pancreatitis, and diarrhea. However, I alone led to 29.2% of diarrhea and 8% of colitis cases. Hepatitis occurred in 9.8% cases under P-I, 4.9% cases under N-I, and 4.4% cases under N followed-by I combinations. This rate was 3% under N alone.

Allergic reactions occurred in 2% cases after N alone and 2.9% cases after N-I combinations. The frequency of severe skin rashes was 3.6% after N-I. However, I alone caused a rash in 31.1% of patients.

Other side effects such as serious infections, diabetes, serious kidney problems, and lung inflammation occurred less often. P therapy was associated with joint pain (12.2%), muscle pain (5.9%), and arthritis (1.2%). N-I was also associated with joint pain (14.6%), muscle pain (11.9%), and muscle spasms (2.2%). 

The bottom line

The study concluded that combination therapies of I, N, and P increase the occurrence of irSEs in patients with advanced melanoma. The authors suggest that physicians should carefully monitor patients during these treatments.

The fine print

This study evaluated results from multiple clinical trials. The definition of irSEs may have varies between trials. 

What’s next?

Please discuss with your doctor if you have concerns regarding side effects from immunotherapy.

Published By :

Frontiers in oncology

Date :

Mar 03, 2020

Original Title :

Potential Immune-Related Adverse Events Associated With Monotherapy and Combination Therapy of Ipilimumab, Nivolumab, and Pembrolizumab for Advanced Melanoma: A Systematic Review and Meta-Analysis.

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