Romain Palich of
Pitié-Salpêtrière Hospital in Paris presented an analysis of cases of KS in people with sustained viral suppression that were reported
to ONCOVIH, a French national multidisciplinary committee that collects data on
cancer among people living with HIV.
This observational study included all reported cases of either a first
diagnosis of KS or a relapse of KS occurring in people who had been on ART for
at least a year and had undetectable plasma viral load (<50
copies/ml).
The committee registered a total of 72 KS cases between May 2014 and December
2017. It was the second most common cancer after lung cancer (96 cases), and
was followed by another AIDS-defining
cancer, non-Hodgkin lymphoma (NHL; 58 cases). These were followed by a variety
of non-AIDS-defining cancers including anal cancer (32 cases), oral cancer (28 cases),
breast cancer (20 cases) and bladder cancer (16 cases). Liver cancer – associated
with hepatitis B and C – was uncommon (9 cases) and there were no reported cases
of prostate cancer.
Of the people with KS, 21 met the viral suppression criteria. Of the
remainder, just over half had a viral load above 50 copies/ml and the rest were
missing data.
Among the 21 people with new or recurrent KS while virally suppressed, 80%
were men. The median age was 54 years; half were born in Africa. They had been
diagnosed with HIV a median of 14 years prior and the median duration of viral
suppression was 3 years.
Of the KS cases, 40% were first-time diagnoses while 60% were relapses,
sometimes many years after the previous occurrence. All patients had KS skin
lesions and many had additional manifestations including lesions of the lymph
nodes (27%), bronchial tubes (18%), bones (18%), stomach or oesophagus (14%), and
mucous membranes of the mouth (5%). Just under half had received treatment for
the current KS episode.
The median CD4 count at the time of KS diagnosis was 449 cells/mm3,
though it ranged as high as 625 cells/mm3. Nearly half had a CD4 count over 500 cells/mm3 when
diagnosed; only 19% had fewer than 200 cells/mm3, the traditional
threshold for advanced immune suppression. The median CD4 level was a bit lower
for new compared with recurrent cases (375 vs 478 cells/mm3, respectively). The median
CD4 nadir, or lowest-ever level was 196 cells/mm3 (ranging from 84 to
329 cells/mm3). The median CD4/CD8 cell ratio was 0.58.
Palich noted
that a related study by the European CD4/CD8 Ratio and Cancer Working Group of
the Collaboration of Observational
HIV Epidemiological Research in Europe (COHERE) looked at the link between CD4
and CD8 levels and the occurrence of KS and NHL in people with viral
suppression. A persistently
abnormal CD4/CD8 ratio despite treatment reflects ongoing immune dysfunction.
This analysis
included more than 58,000 patients who achieved virological control (here
defined as <500 copies/ml) within 9 months after starting ART. The quarter
of patients who experienced restoration of a normal CD4/CD8 ratio along with
CD4 cell recovery were slightly less likely to develop KS. People with a high
CD8 count at baseline had the greatest risk of developing NHL. Those who
experienced virological treatment failure were at much higher risk for both KS
and NHL.
Returning to the ONCOVIH analysis, 14 people started treatment according
to committee recommendations. Seven received anthracyclines (chemotherapy drugs
such as doxorubicin), four received taxanes (the chemotherapy class that
includes paclitaxel) and three couldn't receive either due to intolerability
and tried other therapies. Seventeen patients continued on their current ART
regimen while four were advised to modify their regimen due to drug
interactions or resistance.
Of the nineteen patients with adequate follow-up, six had partial KS
regression or remission, six had stable disease and four experienced disease
progression. Plaich acknowledged that these patients might not be
representative, as more challenging cases might have been disproportionately
referred to the committee.
KS progression despite treatment and the toxicity of conventional
chemotherapy leads some people to a "therapeutic dead end," Palich
said, suggesting that immunotherapies such as PD-1 checkpoint inhibitors might
warrant a pilot study for people with persistent KS that does not respond to
standard therapy.