Σάββατο, 5 Αυγούστου 2017

IMMUNOTHERAPY FOR HIV PATIENTS WITH CANCER

In a small cohort of HIV-positive patients with cancers not related to HIV, immunotherapy drugs that block the PD-1 cancer pathway yielded mixed results. But the treatment was safe.
"This immunotherapy could have a great impact for people with cancer and HIV," said Amelie Guihot-Thevenin, MD, from Hôpital Pitié-Salpêtrière in Paris.
Because people with HIV are often excluded from studies, the safety of immunotherapy in this population has been unclear. But that's changing.
This was one of a handful of small-cohort studies presented during the HIV Cancer and Cure Forum at the International AIDS Society 2017 Conference in Paris, and all showed that immunotherapy drugs for some of the most aggressive and common cancers can be tolerated by people with HIV.
However, whether it is effective and whether this research will eventually lead to immunotherapy for HIV itself is unclear, Dr Guihot-Thevenin told Medscape Medical News.
In this prospective 120-day study, 12 patients with undetectable viral loads and cancer — 11 with non-small-cell lung cancer and one with melanoma — received the PD-1 checkpoint blocker nivolumab (Opdivo, Bristol-Myers Squibb) after traditional chemotherapy had failed.
Because immunotherapies can lead to reactivated immune systems, which can, on occasion, attack organs or cause other immune-related effects, researchers monitored viral loads, CD4 and CD8 cell counts, and immune mediators, such as interleukin-6 and functional T-cells. Blood was drawn at baseline and then on days 14, 30, 60, and 120.
There was one severe infection and one grade 1 adverse event.
'No Immune Syndromes'
"We were afraid of side effects, immune reconstitution inflammatory syndrome, and immune syndromes," said Dr Guihot-Thevenin. "But we had no immune syndromes," she told Medscape Medical News. "We were glad to see that we had no particular side effects in these patients."
The study is small. "We are not 100% sure of the safety of this immunotherapy in these immunocompromised patients," she acknowledged. "We need more patients, but the results of the immunovirological study are really encouraging."
Another study of 30 patients with HIV and non-small-cell lung cancer is in the works, she reported.
Mixed Efficacy
Efficacy results were encouraging as well, she said. Three of the 12 patients had a partial response, four were stable, and five experienced disease progression.
"This is in line with what we observe in immunocompetent patients," she explained.
Although the treatment had little effect on HIV reservoirs in most of the patients — viral loads continued to be undetectable in all patients — one patient saw his reservoir reduced by 90%.
This was "one surprise in the study," said Dr Guihot-Thevenin, although she did not discuss the mechanism of this reduction.
The key, she explained, is that physicians should not try to manage cancer immunotherapy for HIV-positive patients alone. She said she works collaboratively with other infectious disease doctors, oncologists, immunologists, virologists, and pharmacologists to study each patient's case and determine the appropriate therapy.
"Physicians should set up working groups so they can coordinate together and monitor the patients carefully," she said.
Thomas Uldrick, MD, clinical director of HIV and AIDS Malignancies at the National Cancer Institute, said he occasionally hears from physicians with tough cases. They ask him if cancer immunotherapy might be the right option.
It depends on the patient, he said, but the principles of patient selection for any cancer treatment remain the same.
In particular, Dr Uldrick said he watches the functioning of the thyroid and other endocrine organs, which can deteriorate with PD-1 treatment. Other than that, he recommends following the protocol laid out for any patient using checkpoint inhibitors.
In this study, he said, he was left "without a good understanding" of the safety of the agents, although it is clear that there were no profound adverse effects. And there are no predictable drug–drug interactions between checkpoint inhibitors and HIV medications, he added.
"There are a lot of limits in small studies in terms of questions that remain in the field," he told Medscape Medical News. "How effective will it be in the overall population, and do CD4 counts or other immune factors matter?"
Dr Uldrick said he is working on his own PD-1 immunotherapy study, in which people with HIV and cancer are stratified by CD4 count.
"My overall take-away is that we're beginning to get real-life evidence of at least a proof of concept that patients with lung cancer or melanoma and HIV can take these medications safely. And that's important to show," he said.
Dr Guihot-Thevenin and Dr Uldrick have disclosed no relevant financial relationships.
International AIDS Society (IAS) 2017 Conference: Abstract MOPEB0362. Presented July 24, 2017.

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