Pomalidomide helps clear lesions caused by HPV infection
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Low-dose pomalidomide was well-tolerated and helped clear high-grade squamous intraepithelial lesions caused by HPV in patients with and without HIV, according to research from the Conference on Retroviruses and Opportunistic Infections.
“Anal cancer continues to be a significant problem in people living with HIV, despite the availability of effective antiretroviral therapy,” Mark Polizzotto, MD, associate professor and program head of the therapeutic and vaccine research program at the Kirby Institute at the University of New South Wales, said during a virtual presentation.
He explained that anal cancer is typically preceded by high-grade squamous intraepithelial lesions (HSILs), and that there is a “high prevalence of both HPV infection and these high-grade lesions in key risk groups, particularly HIV-positive gay men,” and in other groups, including HIV-negative men who have sex with men and in women who previously had cervical disease.
Polizzotto noted that findings from previous studies suggested regression of HSILs is associated with T-cell response to HPV oncogene E6. Another study found that pomalidomide — an immunomodulatory agent with antineoplastic activity — demonstrated immune activation in Kaposi sarcoma, another type of viral tumor.
To determine if low-dose pomalidomide could enhance immune response to HPV and treat HSILs, Polizzotto and colleagues recruited people who had persistent anal HSILs in the last year. People of any HIV status were eligible, and those with HIV were eligible if they were taking ART and had a controlled viral load. Those included in the study received 2 mg of pomalidomide for 21 days of each 28-day cycle for 6 months.
Researchers assessed the prevalence of histological clearance at the end of therapy — more than 50% clearance in the involved area — along with response after another 6 months of observation. They used flow cytometry to assess immune activation, and 0X40 assay to evaluate antigen-specific CD4+ T-cell response to HPV16 E6 and E7.
Among the 24 participants evaluated in the study, the median age was 54 years, all were men and 38% were living with HIV.
Polizzotto and colleagues found that the overall response was 52% (95% CI, 31-73) at the end of therapy and 63% (95% CI, 40-81) after another 6 months of observation.
They determined that systemic CD4+ T-cell responses did not increase with therapy in HPV E7; responses to HPV E6 did increase during therapy and peaked at day 14; the baseline was 0.06% (IQR; 0.01-0.12) and the median increase at day 14 was 0.13% (IQR, 0.02-0.26; P = .001). Researchers noted that the responses were comparable among those living with HIV.
During the study, adverse events were typically mild and self-limited, including constipation, fatigue and rash.
Polizzotto said that the findings suggest “low-dose pomalidomide was feasible and well-tolerated in people with HSIL and induced durable and continual clearance in people with and without HIV.”
He noted that additional research is needed to assess immunological mechanisms of action in HPV-associated premalignancies. – by Erin Michael
Reference:
Polizzotto M, et al. Abstract 70. Presented at: Conference on Retroviruses and Opportunistic Infections; March 8-11, 2020; Boston.
Disclosures: Polizzotto reports receiving a patent from the Celgene Corporation, research grants/pending grants from the Celgene Corporation and Janssen Therapeutics and consulting/advising fees from Gilead Sciences. Through his institution, he reports receiving research grants/pending grants from ViiV Healthcare.