Dr. Srdan Verstovsek was invited to offer an educational seminar at the ASCO meeting in Chicago last week We had a chance to catch up with him between ASCO
and the start of the European Hematology Association Conference that opens this week in Amsterdam . He gave us a set of the slides he used at ASCO and responded to a few questions as well.
This presentation shouldn’t be entirely new to MPNforum readers since several slides appeared in earlier stories. But of special interest now might be Slide 16 showing what happens when ruxolitinib (now Jakafi) is discontinued.
When Jakafi is discontinued
“Symptoms come back after seven days. If there is more of a response there will be more of a return to baseline for the patient to experience with return of symptoms. The FDA noted the tapering of ruxo may be considered when stopping therapy since some patients may suffer as all the fatigue and weakness come back in seven days.”
Anemia and thrombocytopenia
We asked Dr. Verstovsek how he treated the well documented effects of anemia and thrombocytopenia. Since the JAKs are instrumental in signalling blood production and immune functions, targeting them to reduce splenomegally and MF symptoms impacts those functions as well.
“We treat it as usual,” said Dr. Verstovsek. ” On top of ruxo we add erythropoietin, for example. I suggest you check the EHA abstracts since the German investigators have an abstract reporting on the combination of ruxo and erythropoietin… The combination works. Second option is the use of anabolic steroids like Danazol 200mg two or three times a day, or third option is the use of prednisone for a short time. I usually prescribe a three month regimen of prednisone, starting at 30 mg daily for the first month, 15 daily for second month, and 15 every other day for third month. These are just suggestions based on limited clinical experience, we don’t yet have studies to formally evaluate these combinations…but again I think there will be an abstract on erythropoietin presented at EHA “
The question of longevity extension with ruxolitinib has been on everyone’s mind. We asked about it.
“We do have firm data we can rely on. In phase 3 randomized study between ruxo and placebo, those patients randomized to ruxo had better survival. Very importantly, at the time when survival difference was noted, only two patients (out of more than 150 originally on placebo) were still on placebo as patients crossed over to ruxo therapy. (Switch to ruxo was allowed for worsening of splenomegaly and symptoms when on placebo.)
“Average time to crossing over from placebo to ruxo was 41 weeks. That delay of 41 weeks to get to ruxo therapy caused patients randomized to placebo to have inferior survival. There were almost twice as many deaths among those on placebo arm than those who started on ruxolitinib [16% vs 9%] right away. This difference in exposure to ruxolitinib resulted in a survival advantage that is quite impressive to me.
” In addition, long term survival analysis of patients on Phase 1-2 study enrolled here at MD Anderson — and there were 107 patients — showed survival advantage over 310 patients with myelofibrosis that were treated with conventional therapies in the past in 4 academic centers (MD Anderson and 3 in Italy). These historical control patients were matched for their characteristics to 107 patients treated with ruxolitinib. Therefore, now we have evidence for survival benefit in patients with advanced myelofibrosis from both prospective and retrospective analyses. ”
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