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(ACTRIMS/ECTRIMS) New test to identify PML risk w/Tysabri in MS
By: agate Date: September 29, 2014, 6:24 pm
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From Medscape, September 29, 2014:
[quote]New Test to Identify PML Risk With Natalizumab in MS
Sue Hughes
BOSTON — A new test seems to be able to stratify patients at
risk for progressive multifocal leukoencephalopathy (PML) while
receiving the multiple sclerosis (MS) drug natalizumab more
effectively than anything available at present.
The test is based on observations that patients who develop PML
appear to have very low levels of L-selectin (CD62L) on CD4+ T
cells in the months or years before they develop the condition.
"We believe that very low levels of L-selectin is a predictive
test for the future risk of PML on natalizumab," stated Dr.
Heinz Wiendl, University of Münster, Germany.
He presented the data at the recent MS Boston 2014, the 2014
Joint Americas and European Committees for Treatment and
Research in Multiple Sclerosis (ACTRIMS/ECTRIMS) meeting.
Dr. Wiendl explained that he and his colleagues noticed that
some patients receiving long-term natalizumab had reductions in
levels of L-selectin. "In particular[,] patients who developed
PML tended to have very low levels of L-selectin, so we thought
it might be a good biomarker," he said.
They therefore went back and analyzed blood samples from a
larger group of natalizumab recipients. "We now have data on
1000 patients treated with the drug, of whom 15 have developed
PML," he reported.
"Of these 15 patients, 14 showed very low levels of L-selectin
(less than 21.6) in samples of peripheral blood taken months or
years before PML developed."
Asked for comment on these findings, Robert J. Fox, MD, Mellen
Center for Multiple Sclerosis at Cleveland Clinic in Ohio, said
he thought this was one of the "most exciting developments"
presented during the meeting.
Dr. Wiendl told Medscape Medical News that he is now testing all
patients after 18 months of natalizumab and then every 6 months
thereafter. "If one value is low then the patient is at
significant risk of PML and we stop the drug."
Dr. Wiendl believes that L-selectin is far more selective than
JC virus V (JCV) antibodies for identifying patients at risk for
PML.
"About half of patients test positive for JCV antibodies, but
only about 10% of patients have low levels of L-selectin," he
noted. "JCV positivity puts patients at a risk of about 1 in 100
of developing PML, but with low L-selectin levels the risk is
more like 1 in 10," he estimated.
The L-selectin test is also more reliable in patients who have
had previous immunosuppression, he added.
Synergistic With JCV Antibody Status
Dr. Wiendl is not advocating that L-selectin replace the JCV
antibody test but rather that they be used together. "I see it
as a combined effort, as the 2 markers appear to be
synergistic," he said.
The problem, however, is that the L-selectin test is not easy to
perform. It involves purifying and isolating mononuclear cells
and then performing multicolor flow cytometry. "At the moment
our L-selectin test is just at the transition from academic to
clinical," he noted. It is now undergoing validation in
different cohorts in France and Spain.
Dr. Wiendl's team is offering the test to centers in Germany,
Austria, Switzerland, and Benelux (Belgium, the Netherlands, and
Luxembourg) at present and is open to the idea of expanding the
service to other countries. However, there is a logistical issue
in that the blood has to be processed within 24 to 36 hours so
the mononuclear cells are still viable, which limits long travel
distances to the laboratory. Dr. Wiendl is looking at ways to
commercialize the test to enable more widespread use.
Dr. Fox emphasized the importance of risk stratification for
complications such as PML. "With these complications what we try
to do is risk-stratify and risk-mitigate," he told Medscape
Medical News. "We want to stratify patients to understand their
risk, and then mitigate that risk as best we can. This test
promises to help us do just that."
He said the sensitivity and specificity of the L-selectin test
were reported to be about 90%, "which is very encouraging."
"I would be eager to have the test available for general
clinical use so that we can use that to help guide patients
regarding their risk, and not just predicting the risk but also
perhaps identifying those that are in the early stages of having
developed PML," he added.
More information about the tests can be obtained from contacting
Dr. Wiendl through the hospital's Web site.
______________________________
Dr. Wiendl reports honoraria and consultation fees from Bayer
HealthCare, Biogen Idec, Fresenius Medical Care,
GlaxoSmithKline, GW Pharmaceuticals, Merck Serono, Novartis,
Sanofi-Genzyme BioVentures, and Teva Pharmaceutical Industries;
grants and contracts with Bayer HealthCare, Biogen Idec, the
German Ministry for Education and Research, Deutsche
Forschungsgesellschaft, the Else Kröner Fresenius Foundation,
the Fresenius Foundation, the Hertie Foundation, Merck Serono,
Novartis, the NRW Ministry of Education and Research, the
Interdisciplinary Center for Clinical Studies in Münster,
Germany, the RE Children's Foundation, sanofi-aventis/Genzyme,
and Teva Pharmaceutical Industries. Dr. Fox reports he has
received personal consulting fees from Novartis, Biogen Idec,
GlaxoSmithKline, MedDay, Questcor, Teva, and XenoPort; has
served on advisory committees for Biogen Idec and Novartis; and
received research grant funding from Novartis.[/quote]
This article can be seen here
HTML http://www.medscape.com/viewarticle/832504.
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