A study opens the door to treat cancer with immunotherapy in people living with HIV
50% of the patients obtained a clinical benefit from the treatment and any of them presented severe toxicities. Until now, people living with HIV were excluded from clinical trials with new cancer immunotherapies because it was thought that, since the virus affected their immune system, the therapy could not be appropriate for them.
The JAMA Oncology journal publishes the results of a clinical study that confirms the safety of oncological immunotherapy treatments in people living with HIV, opening the door to the use of these drugs in this group of patients. Until now, people with HIV were excluded from immunotherapy clinical trials because it was considered that the therapy was not appropriate for them as the virus was affecting their immune system.
The work has been promoted by the Spanish Lung Cancer Group (GECP) and has been developed at the IrsiCaixa AIDS Research Institute, the Panoncology Laboratory of the Dr. Rosell Oncology Institute at the Hospital Universitari Dexeus and the Pompeu Fabra University in Barcelona. Eight hospitals in Spain belonging to GECP have participated: the Catalan Institute of Oncology at the Germans Trias i Pujol Hospital in Badalona, the Hospital Clínic in Barcelona, the Virgen del Rocío in Seville, the Hospital La Fe in Valencia, the Hospital La Paz in Madrid, the Hospital Mutua Terrassa in Barcelona, the Hospital General Universitario in Alicante and the Puerta de Hierro in Madrid.
People infected with HIV have a life expectancy similar to that of the general population, as antiretroviral treatments are able to control the virus for life. However, they live in a situation of chronic inflammation that favours the development of tumours at earlier ages. In high-income countries, where access to antiretrovirals is guaranteed, lung cancer is the leading cause of cancer death in people with HIV.
" So far, people with HIV were systematically excluded from trials with new immunotherapies against cancer, so this research is the first in this field in Europe," explains Dr. María González Cao, a member of GECP and a specialist at the Dr. Rosell Oncology Institute at the Hospital Universitari Dexeus. The exclusion was based on the fear that the immunotherapy would reactivate HIV, would have a higher toxicity than in other cases or would further damage the patients' immune system.
González Cao proposed the study when she realized that people with HIV suffering from cancer were in a situation of inferiority in accessing oncological treatments. "Immunotherapies based on the use of antibodies against PD-1 or PD-L1 proteins have revolutionized cancer treatment in the last few years, achieving long-lasting survivors, in some cases even cures, in 20-50% of patients affected by advanced and metastatic tumors", she explains. "We started the study because we wanted to offer the same opportunities to all patients," she adds.
Clinical benefit to patients
The work included 20 patients with cancer and HIV infection receiving antiretroviral medication. Fifteen of them had lung cancer, 2 melanoma, 2 anal carcinoma and 1 bladder cancer.
The trial shows that Durvalumab, an antibody against the PD-L1 protein, is safe and active in people with HIV infection. Fifty percent of the patients treated, 75% with lung cancer, had a clear clinical benefit, suggesting at least the same proportion of success cases as in patients without HIV. Some of the study participants are long-term survivors who are now maintaining their response to treatment and are free of macroscopic tumor disease. None had serious drug-related toxicities.
According to Dr. Rafael Rosell, the study's principal investigator: "Initial data suggest that there may be even better activity and tolerance of immunotherapy than in other patient populations. This is something we need to continue exploring, as it may have implications for the development of new treatments for the general population.
Effects on HIV
For HIV, the results indicate that Durvalumab administration did not increase viral load in the blood of any of the patients, and that CD4 and CD8 immune cell levels remained stable.
The work is also studying the drug's effect on HIV. "We want to study whether immunotherapy has been able to have a beneficial effect on patients' viral loads. Anti-PD-1/PD-L1 therapies, by strengthening the immune system, can theoretically be effective in a multitude of processes where immunity plays a key role, such as viral infections. But we are still in an early stage of study", explains Dr. Javier Martínez-Picado, ICREA researcher at the IrsiCaixa AIDS Research Institute.
For Dr. Mariano Provencio, president of the GECP and head of Oncology at the Puerta de Hierro Hospital in Madrid, "from the GECP it is an honor to promote independent studies that improve the life expectancy of lung cancer patients".