VICC leading first global study of MDS/MPN overlap syndromeSep. 24, 2020, 8:52 AM
by Tom Wilemon
Overlap syndromes are distinct blood cancers that present with features of both myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN).
The most common of these myeloid overlap syndromes is chronic myelomonocytic leukemia (CMML). MDS/MPNs are difficult to treat and typically have poor prognosis. Vanderbilt-Ingram Cancer Center is leading the first ever cooperative international trial for these rare cancers.
The ABNLMARRO initiative (A Basket study of Novel therapy for untreated MDS/MPN and Relapsed/Refractory Overlap Syndromes — abnlmarro.org) is a study formed by the MDS/MPN International Working Group (IWG) that will test therapies for CMML and other MDS/MPN Overlap syndromes.
“This is the first study for patients with CMML and other MDS/MPNs that involves sites in both Europe and the United States,” said principal investigator Michael Savona, MD, professor of Medicine and Cancer Biology and director of Hematology Research at Vanderbilt-Ingram Cancer Center (VICC). “The goal with ABNLMARRO is to grow a consortium of sites around the world to provide access to novel drugs for these patients with rare diseases. MDS/MPN experts from the US, Europe, Japan, Canada, South America and Central America have joined the MDS/MPN IWG in hopes to build this consortium. Hopefully, this is something we are going to be able to expand as we grow our clinical trial capability.”
Setting up the consortium first required establishing response criteria for potential therapies. The criteria needed to be different than those for MDS, MPN and even CMML, which accounts for about 70% of overlap syndromes. Rarer forms of overlap syndrome required response criteria that had not been quantified.
“When we started with the MDS/MPN IWG in 2012,” Savona said. “One of our first goals was to write response criteria for these diseases because for us to develop drugs for people who have these diseases, we knew no companies would give us the drugs to study for MDS/MPN until we had response criteria, which is reasonable.”
In 2015, the MDS/MPN IWG issued the first proposed response criteria, which established treatment goals for potential therapies for overlap syndromes. It was a complicated task because of the many types of overlap syndromes.
“With the published response criteria, small biotech and pharmaceutical companies are opening up to the options of studying their novel compounds in order to improve outcomes for MDS/MPN overlaps,” Savona said. The first drugs to be studied in ABNLMARRO are the recently approved ASTX727+cedazuridine (oral DNA methyltransferase inhibitor) together with the JAK1 inhibitor, itacitinib. ABNLMARRO expects to launch the clinical trial this fall.