Immunotherapy For Small Cell Lung Cancer
Interest in immunotherapy for small cell lung cancer was driven by the incidence of paraneoplastic syndromes (autoimmune phenomena) that occur with high frequency in this disease. Vaccines have been tried but without clinical benefit.
CTLA-4 blockade with ipilimumab, which is very effective in melanoma, was not effective in phase three trials for small cell lung cancer.
PD1 blockade has been the first immunotherapy to prove efficacy in small cell lung cancer.
Pembrolizumab in second line setting has shown a response rate of 35% much improved compared to 10% response rate with second line chemotherapy. Progression-free survival was 10.3 months with pembrolizumab compared with six months with chemotherapy. This also translated in improved overall survival. The drug is well tolerated in general. The most common side effects are fatigue, cough, shortness of breath, nausea, rash, vitiligo and decreased appetite.
Nivolumab is another monoclonal antibody used to treat small cell lung cancer either as single agent with a response rate of 10% or in combination with ipilimumab increasing the response rate to 23%. Nivolumab is a human IgG4 anti-PD-1 monoclonal antibody that stimulates the immune system to attack cancer cells.
Nivolumab is tolerated very well. Rarely, it can cause the immune system to attack normal tissues causing pneumonitis, colitis, hepatitis, and hormone gland problems, rash, nephritis and encephalitis.
Infusion reactions can occur as well pay attention to chills, shortness of breath, itching, fever, and/or dizziness. The infusion needs to be stopped immediately in the event of an allergic reaction.
In addition to being effective and well tolerated these new monoclonal antibodies caused some durable responses.
Currently combining natural killer cells with cytokine-induced killer cell is being investigated, and the results have been encouraging compared to chemotherapy with promising duration of response.