A 58-Year-Old Woman with Polycythemia Vera - Episode 7

Ruxolitinib: Adverse Events & First-Line Plausibility

Prithviraj Bose, MD:Fortunately, ruxolitinib is a well-tolerated drug. In my experience, patients complain a little bit about the weight gain, which is expected. It’s important to check their lipid levels. It’s important to advise them that they need to pay attention to their cardiovascular risk factors, not just because they’re on rux [ruxolitinib] but because they have PV [polycythemia vera] as well. So it’s important to aggressively manage cardiovascular risk factors and know that they’re on a drug that will actually increase cholesterol and weight. Occasionally, you run into a situation where non-melanoma skin cancers become an issue, and the RESPONSE trials actually show that if patients had a history of this, then that is more of an issue. So that’s something to be careful about. Fortunately, it’s not a very common occurrence, but it’s something that one has to be aware of because clearly, the immunosuppressive effects of JAK inhibition can increase that risk. Otherwise, you know, you can get headaches, you can get some bruising, some dizziness. But really, in my practice, these have hardly ever been significant issues or led any patient to discontinue.

We now have 5 years of data from the RESPONSE trial. This was presented at ASH 2018 [the American Society of Hematology Annual Meeting & Exposition], and the efficacy and safety are holding up. The probability of maintaining the hematocrit control, spleen volume reduction, all of that—the hazard ratios are quite favorable. Now we have, as I said, 256 weeks, so that’s a pretty good follow-up. No new safety signals have emerged since the 80-week analysis. So again, that’s pretty reassuring not only that the drug works for a long time but also that no new concerning adverse effects develop. So I think with 5 years of follow-up, we have pretty reassuring data at this point.

Rux [ruxolitinib] is currently approved for hydroxyurea-resistant or -intolerant patients, so that’s a second-line indication. It’s interesting to speculate on whether rux [ruxolitinib] could become a frontline drug. One has to consider, however, that hydroxyurea resistance or intolerance is not supercommon. So right now, it’s been suggested that about 20% of patients develop hydroxyurea resistance or intolerance. So, clearly, rux [ruxolitinib] will work in the frontline, I would think, because the mechanism makes sense. If it has worked in the second-line setting, it should work in the frontline setting.

From the viewpoint of the competitive landscape of drug development, there is an agent called ropeginterferon-alfa-2b, which is being developed in the frontline setting and recently got a positive opinion from the EMA [European Medicines Agency]. I believe there will be trials in the United States as well. So this is a drug, it’s an interferon formulation that actually was shown to be noninferior to hydroxyurea at 1 year in the frontline setting. And then with 2 and 3 years of follow-up, it actually seemed to be better. So I would assume that something similar would need to be done versus hydroxyurea in the frontline setting for such a development path for ruxolitinib.

Transcript edited for clarity.

Case: 58-Year-Old Woman Diagnosed With Polycythemia Vera

November 2018

  • A 58-year old woman presents to PCP complaining of abdominal pain, dizziness and headaches
  • PE: BP 140/85; Splenomegaly ~6 cm below left costal margin
  • PMH: No prior history of thrombosis
  • Lab values:
    • HGB: 17.1 g/dL
    • Hct: .50 L/L
    • RBC: 71 x 1012/L
    • WBC: 13.2 x 109/L
    • Serum EPO: 4.1 mU/mL
  • Bone Marrow Biopsy: Erythroid hyperplasia
  • Cytogenetics: JAK-V617Fmutation