Efficacy of Navitoclax and Ruxolitinib | Naveen Pemmaraju, MD | EHA 2024

Hi everyone, I'm Dr. Navin Pamaraju, professor of leukemia at the MD Anderson Cancer Center in Houston, Texas. And I specialize in research for patients with rare diseases including AML leukemia, myeloproliferative neoplasms, including myelofibrosis and BPDCN. Here at the IHA 2024 meeting in Madrid, Spain, I have the honor on behalf of my colleagues to present data for an international phase three randomized study in the field of myelofibrosis. This study, called the Transform 1, is one of the first studies to give combination chemotherapy, so two different drugs, to our patients with myelofibrosis who've never seen prior JAK inhibitor therapy. This was a large study, 252 patients were enrolled, and in a one-to-one randomization, patients either received the investigational arm, which is ruxolitinib, the standard of care, plus nevitaclax, that's the investigational agent, versus ruxolitinib and placebo. Now, in this study, what we showed, and it was updated at the ASH meeting as well in the last six months, is that patients in the investigational arm, that is the combination arm, nevitaclax, showed a two-fold improvement in their spleen volume reduction, 35% at week 24. That's the key primary endpoint in most of our studies, and so that represents a doubling of the control group, which was only in the 31.5% range, 60 plus percent for the nevitaclax arm. Now, nevitaclax is not yet FDA-approved for any indication. It's an oral agent that targets BCLXL, which is a new pathway beyond JAK inhibitors, and so it represents a potential partner to combine with the backbone or standard therapy. All of these studies are ongoing. The data will continue to mature, but overall, this represents a new field of potential investigation for our patients, which is called disease modification. But what does that mean? Well, with the JAK inhibitors as a single agent or monotherapy, the approved drugs, many patients enjoy and derive benefit of reducing the spleen, improving the symptoms, but most patients, by and large, are not cured by these single agent modalities alone. They need to be paired with something else, such as stem cell transplant. So we and others are hoping to aim to add to the toolkit to see if there are other chemo drugs that can be added to the JAK inhibitors for increased benefit for our patients.