Nivolumab demonstrates antitumor activity for HIV-positive Kaposi sarcoma

Nivolumab induced antitumor activity with low toxicity among a small cohort of patients with HIV-positive Kaposi sarcoma, according to preliminary study results presented at the ASCO-SITC Clinical Immuno-Oncology Symposium.

Perspective from Seth M. Pollack, MD

Kaposi sarcoma is a virally mediated, incurable malignancy developed from cells that line lymph or blood vessels that is associated with HIV.

Natalie Galanina, MD, assistant professor of medicine at UC San Diego Health, and colleagues sought to determine the safety and efficacy of checkpoint blockade with nivolumab (Opdivo, Bristol-Myers Squibb) among a cohort of eight patients with HIV-positive Kaposi sarcoma.

All patients (median age, 45.5 years; range, 38-63) were male and were receiving anti-retroviral therapy. Fifty percent of patients had early-stage disease, and patients had received a median of one prior therapy.

Patients received at least one IV dose of 3 mg/kg nivolumab on days 1 and 14 of a 28-day cycle.

Researchers monitored patients for treatment efficacy, toxicity and for any effects on immune function. They also measured PD-L1 expression retrospectively.

The median follow-up at the time of analysis was 3.5 months.

Five patients (62.5%) achieved a response, which included one complete remission and four partial remissions. The other three patients had stable disease.

Researchers observed low PD-L1 expression in three of four patients with available data.

Seventy-five percent of patients had preserved CD4 count — CD4 count was a median of 297.5 (range, 83-755) at baseline and 378 (range, 142-603) after therapy initiation — and undetectable HIV viral load. Median HIV viral load was 20.5 copies/mL (range, 0-116,706) at baseline and 64 copies/mL (range, 0-1,390,000) posttherapy.

Commonly observed adverse events included fatigue, gastrointestinal discomfort, pruritis and onycholysis. No grade 2 or higher toxicities occurred, and no patients discontinued treatment.

Researchers observed overall improvement in CD4 counts (median, 297.5 vs. 378).

Reference:

Galanina N, et al. Abstract 63. Presented at: ASCO-SITC Clinical Immuno-Oncology Symposium; Jan. 25-27, 2018; San Francisco.

Disclosures: Galanina reports no relevant financial disclosures. One author reports consultant/advisory roles with Actuate Therapeutics, Loxo and Sequenom; stock and other ownership interest in CureMatch; and research funding from Foundation Medicine, Genentech, Guardant Health, Incyte, Merck Serono, Pfizer and Sequenom.

Perspective

Seth M. Pollack, MD

This is an important study because it demonstrates PD-1 blockade can be an option for patients with refractory Kaposi sarcoma, even for patients with low CD4 counts. This will have rapid clinical impact. Kaposi sarcoma is a very rare disease and can be very difficult to treat, and this will give us a new therapeutic option for these patients.

Although the treatment was well tolerated, this remains a strategy for refractory patients. The most important aspect in managing Kaposi sarcoma remains controlling a patient’s underlying HIV when appropriate. Standard chemotherapy options like liposomal doxorubicin remain the first choice. However, for refractory patients, or for patients unable to tolerate chemotherapy, PD-1 blockade is a good choice.

In the future, it will be important to look at PD-1 blockade in the context of other treatment strategies. Because PD-1 blockade is generally very well tolerated, it may ultimately make sense to move it up into the front lines of treatments for Kaposi sarcoma.

Seth M. Pollack, MD

Fred Hutchinson Cancer Research Center

Seattle Cancer Care Alliance

Disclosures: Pollack reports consultant roles with Amgen, Eli Lilly and Nectar, and research support from EMD Serono, Epizyme, Immune Design, Karyopharm, Merck and Presage.