When mesothelioma recurs, patients may face limited treatment options. Researchers at Memorial Sloan Kettering Cancer Center (MSK) are currently working to address this issue. The MSK research team investigated a new combination immunotherapy for second-line treatment of pleural mesothelioma.
The treatment involves CAR T-cell therapy followed by immune checkpoint inhibition. Patients undergoing this treatment had a median survival of nearly two years. Compared to earlier second-line pleural mesothelioma treatments, patients receiving this new combination lived more than a year longer than average.
Understanding CAR T-Cell Therapy and Immune Checkpoint Inhibition
CAR T-cell therapy is a medical treatment that uses immune cells to fight cancer. Doctors create CAR T cells using the patient’s own T cells, a type of immune cell.
The patient’s cells learn how to make a chimeric antigen receptor (CAR). The CAR helps the T cells recognize and attack the patient’s specific form of cancer.
The cells multiply in the lab, creating an abundant supply of cancer-targeting T cells. Then, doctors give the cancer-attacking T cells back to the patient.
Immune cells have checkpoints designed to keep them from attacking a person’s own cells. Cancer cells can exploit this checkpoint to keep immune cells from attacking cancer.
Immune checkpoint inhibitors are drugs that shut down immune checkpoints, allowing immune cells to attack cancer cells.
In this study, doctors used a checkpoint inhibitor called pembrolizumab. Pembrolizumab blocks the PD-L1 immune checkpoint.
Doctors Combined Immunotherapies to Overcome CAR T Cell Shortcomings
CAR T-cell therapy has successfully treated a number of blood-related cancers. However, it has not proven as effective in treating solid tumors, such as mesothelioma. Researchers have suggested several explanations for CAR T-cell therapy’s ineffectiveness against solid tumors. These explanations include:
- CAR T cells do not recognize all solid tumor cells. CAR T cells may not be able to attack a portion of tumor cells.
- CAR T cells may not migrate past the outer layers of the tumor. CAR T cells may entirely miss cancer cells further inside the tumor.
- Solid tumors may create an environment that stops the CAR T cells from doing their job. Researchers call this T cell exhaustion. The tumors effectively “tire out” the CAR T cells. In some cases, they may stop attacking cancer altogether.
In the MSK study, researchers attempted to address the issue of T cell exhaustion. They did so by treating patients with a checkpoint inhibitor after CAR T-cell therapy. Doctors administered pembrolizumab (Keytruda®) about six weeks after CAR T-cell treatment.
The researchers found evidence that pembrolizumab improved the function of CAR T cells. Pembrolizumab may have also helped other immune cells attack mesothelioma tumors. Together, these effects may have contributed to the efficacy of this immunotherapy combination.
CAR T-Cell Therapy Followed by Pembrolizumab (Keytruda®) Achieved 23.9 Month Median Survival
All study participants were pleural mesothelioma patients that had previously undergone at least one form of anti-cancer treatment. More than 70% of these patients had late-stage disease.
- Number of Patients: 18
- Median Age: 70 years
- Gender: 15 male, 3 female
- Epithelioid Cell Type: 94%
- Stage III-IV: 72%
- Prior Lines of Treatment: 1 to 6
First, doctors treated the participants with CAR T-cell therapy. About six weeks later, patients received pembrolizumab.
Median survival for patients receiving the immunotherapy combination was 23.9 months. In prior studies, median survival for second-line treatment of pleural mesothelioma reached 7.9 months.
This means CAR T-cell therapy with pembrolizumab extended survival by more than a year versus other therapies.
CAR T Cell and Pembrolizumab (Keytruda®) Combination Still Under Investigation
Although the results of this MSK study are promising, this therapy is not yet widely available. Researchers will likely perform several more studies before this combination can be approved by the United States Food and Drug Administration (FDA).
In the meantime, patients interested in this treatment may be able to access it through clinical trials. Any patient interested in this immunotherapy combination should discuss treatment options with their mesothelioma doctor. They can help the patient make an informed decision for their unique situation.