Treatment with an immune checkpoint inhibitor appears to be well tolerated and may work as well for HIV-positive people who have cancer as it does for those without HIV, researchers reported at the European Society for Medical Oncology (ESMO) 2018 Congress this week in Munich.
"Although the response data is fairly consistent with results obtained with the same drug among other [HIV-negative] cancer patients, the size of our sample and the length of follow-up do not allow us to draw any conclusions regarding efficacy," Aurélien Gobert of Groupe Hospitalier Pitié Salpêtrière in Paris said in an ESMO press release.
Immunotherapy – treatment that help the immune system fight cancer – is ushering in a new era in cancer treatment, but current therapies do not work for all individuals or for all types of cancer.
Gobert and colleagues assessed the efficacy and tolerability of the immune checkpoint inhibitor nivolumab (Opdivo) among 470 people in the French national CANCERVIH database. These cases were presented to ONCOVIH, a national multidisciplinary committee that consults on cancer in people living with HIV.
As HIV-positive people live longer thanks to effective antiretroviral therapy, non-AIDS cancers have become a growing cause of morbidity and mortality. There has been little research to date on immunotherapy for cancer in people with HIV – and HIV-positive people have typically been excluded from clinical trials of new cancer therapies – but case reports are starting to accumulate.
Nivolumab is a monoclonal antibody that blocks the PD-1 receptor, an immune 'checkpoint' on cytotoxic T-cells. (CD8 killer T-cells are the immune system's main cancer fighters, while CD4 helper T-cells are the primary target of HIV.) The drug is currently approved for several types of cancer including metastatic melanoma, Hodgkin lymphoma, non-small cell lung cancer, and advanced bladder, kidney and liver cancer.
PD-1 plays a role in regulating immune function, dampening down overactive immune responses that could harm healthy issue. Some tumours can exploit the PD-1 mechanism to turn off immune responses against them. Drugs that block the interaction between PD-1 on immune cells and its binding partner, known as PD-L1, on cancer cells can release the brakes and restore T-cell activity – both against the cancer and sometimes against normal tissue, resulting in immune-mediated side-effects. The PD-1 system and anti-PD1 agents are also being explored in HIV cure research.
Checkpoint inhibitors work best against 'hot' tumours that attract many immune cells. If T-cells are not present in the tumour, the drugs cannot boost their activity. It is unclear whether changes in immune function in people with HIV could reduce the effectiveness of these drugs, or conversely, lower the risk of immune-mediated side-effects.
Gobert's team looked at outcomes among 35 HIV-positive individuals for whom immunotherapy had been considered since 2014. Of these, 19 people with metastatic non-small cell lung cancer and one person with metastatic melanoma were treated with nivolumab. Most were men and their median age was 60 years.
At the time of their cancer diagnosis, 17 of the 20 treated people had undetectable HIV viral load and the median CD4 T-cell count was 338 cells/mm3. They received a median of six nivolumab infusions, with the longest treatment involving more than 50 injections. Follow-up continued for a median of about 11 months (ranging from one to 28 months).
No deaths due to drug toxicities or immune-related adverse events were observed, according to the report. Viral load and CD4 count generally remained stable, although one person did have a rise in HIV RNA and a falling CD4 count after stopping antiretroviral therapy.
During the follow-up period, four people (20%) achieved partial tumour shrinkage, two (10%) had stable disease and 11 (55%) experienced disease progression. There were no complete responses (i.e. individuals with no remaining evidence of disease). Three people (15%) could not be evaluated for treatment response. These response rates were similar to those for HIV-negative people with this cancer observed in the CheckMate-057 trial.
Based on these preliminary data, the researchers concluded, "treatment with anti-PD-1 inhibitors seems to be feasible in people with HIV." They recommended that antiretroviral therapy should not be interrupted and viral load and CD4 count should be monitored during treatment with checkpoint inhibitors.
"We know that few patients respond to immunotherapy, but those who do respond for long periods of time and thus have significantly improved survival," Gobert said. "This seems to have been the case for the melanoma patient in our cohort, but the study is too recent for us to quantify survival rates at this time."
Gobert A et al. Tolerance and efficacy of immune-checkpoint inhibitors for cancer in people living with HIV (PWHIV). ESMO Congress, abstract 1213_PR, 2018.