Immunotherapy is a cancer treatment available to people with mesothelioma primarily through clinical trials. When combined with other anticancer treatments, such as chemotherapy and surgery, immunotherapy can improve survival rates and reduce symptoms for people with mesothelioma.
Immunotherapy is an experimental treatment for mesothelioma. It is not yet a part of standard, first-line treatment for the cancer, but medical research is getting closer to making it a reality.
Certain immunotherapy drugs, such as Keytruda and Amatuximab, have helped some people live for years with mesothelioma. Immunotherapy drugs are only available through mesothelioma clinical trials or compassionate use programs.
Immunotherapy can enhance the immune system response to mesothelioma cancer, but it has not been able to cure the cancer. Research is integrating immunotherapy as part of a multimodal treatment plan to better manage mesothelioma like a chronic disease.
Several immunotherapy agents, including Keytruda, Opdivo and Yervoy, have shown promising anticancer activity against mesothelioma in recent clinical trials.
Keytruda is an immunotherapy drug used to treat lung cancer, and it’s under investigation to treat mesothelioma. Trials show Keytruda is effective against mesothelioma in certain patients and helps them live longer when the cancer recurs after first-line treatment. One mesothelioma survivor says surgery and Keytruda saved his life, and another survivor says chemotherapy, Keytruda and surgery saved her life.
Opdivo and Yervoy help people live longer after mesothelioma recurs, meaning these drugs might prove more effective as a second-line treatment than chemotherapy. Less than one-third of mesothelioma patients live longer than three months after mesothelioma recurs, but a French clinical trial reported that half of their participants lived longer than three months with the combined treatment of Opdivo and Yervoy.
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Immunotherapy is the hottest topic in cancer research and is widely considered the future of cancer treatment. Aside from the ultimate benefit of potentially keeping cancer in control, the benefits of immunotherapy include:
Different types of immunotherapy have been tested on mesothelioma since the 1970s. Recent breakthroughs in research, such as the development of Keytruda and other immune checkpoint inhibitors, made immunotherapy a more viable treatment option for mesothelioma.
Immune checkpoint inhibitors are drugs that stop cancer cells from hiding from the immune system. Checkpoint inhibitors are made of antibodies that unmask cancer cells and allow the immune system to recognize them and attack.
The most promising checkpoint inhibitors in mesothelioma research currently include Keytruda, Opdivo and Yervoy. Another checkpoint inhibitor called SS1P controlled mesothelioma tumors in certain patients but not enough to warrant further study.
There are two types of cancer vaccines:
Research is underway in Hawaii to develop a preventative mesothelioma vaccine.
Clinical trials have studied some therapeutic vaccines for mesothelioma, and two vaccines in particular, known as CRS-207 and WT1, have shown the most promise.
A 2016 study showed that the combination of chemotherapy and CRS-207 controlled tumor growth longer than chemotherapy alone. Another clinical trial is investigating the combination of CRS-207 and Keytruda.
A phase II clinical trial of the WT1 vaccine reported significantly longer survival and better tumor control among participants who received the vaccine versus those receiving a placebo.
Monoclonal antibody therapy (mAb) is the most commonly used form of cancer immunotherapy, but it’s not necessarily the most common immunotherapy for mesothelioma. It is considered a targeted therapy because it is focused on a single site within the cancer cell, either an antigen on the surface of the cell or an enzyme or protein within the cell.
Amatuximab (known as MORAb-009) is a monoclonal antibody that made it to a phase II clinical trial on mesothelioma patients. Not enough patients responded to the therapy to warrant a phase III trial. Overall survival was 14.8 months, and the average survival for mesothelioma is around one year.
One mesothelioma patient, Andy A., responded abnormally well to Amatuximab during a clinical trial. Andy was allowed to stay on the drug for years after the study technically ended because it continued to keep his mesothelioma in control. When the drug suddenly stopped working, Andy turned to complementary therapies including cannabis oil.
Other types of immunotherapy studied on mesothelioma include adoptive cell transfer, cytokines and Bacillus Calmette-Guerin.
Transferring live, whole immune cells into patients is a practice that researchers use on patients with advanced metastatic melanoma or renal cell carcinoma. Adoptive cell transfer is also being investigated for use in patients with mesothelioma.
Injection of dendritic cells following chemotherapy has been tested in a phase I clinical trial. Ten patients previously treated with cisplatin and pemetrexed tolerated the therapy well, and an immune response was documented in the study’s participants.
Cytokines, such as tumor necrosis factor, interferon and interleukin-2, are used in immunotherapy to kill cancer cells or stop the birth of new cells. They interact directly with the tumor cells and are given individually or in combination to take advantage of the effect of all of them working together, which is more effective than what each can do individually.
Examples of using cytokines to boost the immune response include:
Lymphocytes are white blood cells. The three types include:
During the 1970s, researchers discovered that administering weakened forms of a mycobacterial strain called bacillus Calmette-Guerin (BCG) was effective in treating cancer. BCG is made from a live strain of tuberculosis virus found in oxen and cows.
BCG is approved for treating bladder cancer and as a vaccine for tuberculosis. In the 1970s and ’80s, studies were conducted on its usefulness as a treatment for mesothelioma and pleural effusions. In one study, BCG was injected into mesothelioma patients and repeated monthly. The injections prevented reaccumulation of fluid in the lung cavity.
Another study involved 30 patients with various stages of malignant pleural mesothelioma. Patients first underwent a thoracotomy, in which as much of the cancerous tissue as possible was removed. Following chemotherapy or radiation, BCG injections were administered every three weeks. After six weeks, the treatment interval was lengthened to four, five and then six weeks.
Twenty-eight out of 30 patients continued to receive injections, and they reported the injections made them feel much better and their pain was significantly reduced. The researchers noted the best prognosis was achieved when BCG was used in patients with a relatively light tumor load who had undergone thoracotomy. These patients survived an average of 21.5 months, and one patient was still living six years after treatment.
While BCG showed early promise decades ago, it is not currently being offered as a treatment for mesothelioma. However, current immunotherapy studies have been conducted with other forms of mycobacterium, including SRL 172, which failed to find it effective against mesothelioma and non-small cell lung cancer.
A basic understanding of the immune system helps people understand how immunotherapy works. The immune system has evolved to protect the body from foreign pathogens (like viruses and bacteria) and disease development, and it also removes damaged or dead cells. Your immune system recognizes internal and external causes of illness, including cancerous cells.
At birth, your immune system is preloaded with all sorts of information to protect you in the world. Your immune system develops as you grow, and it learns to recognize foreign pathogens like viruses and bacteria. These two parts of the immune response are called passive and active, respectively.
Passive immunotherapy uses the kind of immune cells you were born with to attack cancer, while active immunotherapy teaches your body to recognize and kill the cancer.
Immunotherapy will likely become an effective treatment option for mesothelioma in the future, especially when combined with other cancer therapies. Some studies have combined immunotherapy with chemotherapy or surgery, and recent results indicate a significant survival benefit in certain patients.
Researchers have discovered a direct correlation between penetrating lymphocytes and mesothelioma prognosis, indicating that enhanced immune response may improve patient outcome. Additionally, laboratory studies of asbestos suggest the mineral compromises immune cells, which could contribute to its carcinogenic effect. Preventative cancer vaccines for people exposed to asbestos could offer chemopreventative benefit in the future, but identifying who could biologically benefit from such therapy is currently challenging.
The exciting news is that immunotherapy is available to people with mesothelioma through clinical trials and compassionate use programs. If your oncologist hasn’t brought up the prospect of immunotherapy, be sure to bring it up and ask if there are any clinical trials near you.
I believe immunotherapy will become the fourth pillar of treatment for mesothelioma [joining surgery, radiation and chemotherapy]. It could help turn mesothelioma into a chronic disease that people can live with for a long time.
— Dr. Dan Sterman
Karen Selby joined Asbestos.com in 2009. She is a registered nurse with a background in oncology and thoracic surgery and was the director of a tissue bank before becoming a Patient Advocate at The Mesothelioma Center. Karen has assisted surgeons with thoracic surgeries such as lung resections, lung transplants, pneumonectomies, pleurectomies and wedge resections. She is also a member of the Academy of Oncology Nurse & Patient Navigators.
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