A month after the FDA approved a new drug combination for pleural mesothelioma, scientists are discovering more about who might benefit the most from this treatment.
A new report in EBioMedicine suggests that the success of the new drug combination for mesothelioma depends on the presence and activation of special immune system cells.
Researchers in the Netherlands found that patients with enough of the right kind of T-cells had the best results. The findings could help doctors screen out mesothelioma patients who are less likely to benefit.
The Long-Awaited New Drug Combination for Mesothelioma
The two medicines in the new drug combination for mesothelioma are nivolumab (Opdivo) and ipilimumab (Yervoy).
The FDA approved a mix of the two immunotherapy drugs in October. They are the first new drugs to win approval for mesothelioma since Alimta came out in 2004. The new drug combination is for pleural mesothelioma patients who are not eligible for surgery.
Opdivo and Yervoy are monoclonal antibodies. Yervoy helps activate and proliferate cancer-killing T-cells. Opdivo makes it easier for existing T-cells to discover the tumor. Together, the two medicines appear to slow down the growth of mesothelioma tumors.
In a study of the two drugs, mesothelioma patients who received the new drug combination lived a median of 18 months. At one year, almost 70 percent of the patients on this protocol were still alive. Only 58 percent of the chemotherapy patients in the study lived that long.
Predicting Response to Opdivo/Yervoy Therapy
The key to using the new drug combination most effectively is to choose mesothelioma patients who are most likely to respond. At this point, doctors are still not sure how to do that.
But the new study appears to shed some light. Researchers at the Erasmus Medical Center Rotterdam performed immune cell profiling on mesothelioma patients. The goal was to understand the characteristics of their T-cells.
Then they gave the new drug combination to some of the mesothelioma patients. Others received only nivolumab.
“Patients that responded to combination treatment had low frequencies of naive CD8 T cells and high frequencies of effector memory CD8 T cells that re-expressed RA (TEMRA) at screening,” writes Joanne Mankor, a lead author on the study.
These special “TEMRA” T-cells are more prevalent in cord blood than they are in adult blood. In adults, they have been linked to protective immunity against certain diseases and pathogens. The researchers say testing for TEMRA levels could help doctors know which cases of mesothelioma are most likely to respond to the Opdivo/Yervoy protocol.
“TEMRAs can play a key role in explaining and predicting clinical benefit upon aPD-1/aCTLA-4 combination treatment,” writes Dr. Mankor.
The study was funded by Bristol-Myers Squibb, which makes the new drug combination for mesothelioma.
Mankor, J, et al, “Efficacy of nivolumab and ipilimumab in patients with malignant pleural mesothelioma is related to a subtype of effector memory cytotoxic T cells: Translational evidence from two clinical trials”, November 6, 2020, EBioMedicine, Epub ahead of print, https://www.sciencedirect.com/science/article/pii/S2352396420304163
Seddiki, N, et al, “Persistence of naive CD45RA+ regulatory T cells in adult life”, April 1, 2006, https://ashpublications.org/blood/article/107/7/2830/132078/Persistence-of-naive-CD45RA-regulatory-T-cells-in
“FDA Approves Drug Combination for Treating Mesothelioma”, FDA Press Announcement, October 2, 2020