DR CORTES: The original studies, such as COMFORT-I, were limited to patients with platelet counts of at least 100K/µL, and there’s a recommendation for a titration of the dose depending on the platelet count. If the patient had a platelet count of more than 200K/µL, then you would use 20 mg BID. If the patient had 100 to 200K/µL, you would use 15 mg BID.

The label doesn’t say that you shouldn’t use ruxolitinib for patients with platelet counts lower than 100K/µL, but few data exist in this setting. A study has been presented for patients with platelet counts between 50 to 100K/µL, for whom lower doses of ruxolitinib were used. We have started out at 5 mg BID with a gradual escalation in dose depending on how the patient tolerates the drug. We have observed that patients tolerate this approach well and can benefit as much as those with higher platelet counts. So I would definitely use ruxolitinib for these patients with lower platelet counts.

When initiating ruxolitinib we need to carefully monitor patients because they can develop worsening anemia or thrombocytopenia. Sometimes we need to hold therapy or adjust doses, but it should not be done for minimal changes.

DR STEENSMA: I follow the instructions on the package insert with respect to dosing ruxolitinib on the basis of platelet counts. One of the challenges we face with recommendations in a package insert is whether or not they reflect reality. We’re somewhat obliged to follow those recommendations or justify why we’re not doing so. From the dose-finding study for patients with lower platelet counts — the 50- to 100K/µL range — ruxolitinib at 10 mg BID seems to be the “sweet spot.” If you have to lower the dose below that — unless it’s because of poor renal clearance — the effectiveness of ruxolitinib is simply not as good.

DR CERVANTES: According to the data we have available, patients with moderate thrombocytopenia may be treated with ruxolitinib but at a lower starting dose. The lower dose is 5 mg BID, and you can try to escalate the dose to 10 mg BID. At a low starting dose that is escalated to a higher dose, ruxolitinib works in a proportion of patients.

The drug is well tolerated, with nonhematologic effects being minimal to moderate and the main side effect being hematologic toxicity. You never find a sudden decrease in the number of platelets, for instance. It happens in a progressive fashion and you can adjust. Of course, at a certain platelet count you can stop the drug and then try to restart at a lower dose when the platelet count goes up. If you must stop ruxolitinib, do not interrupt it abruptly but instead taper the drug.

DR MESA: I am most concerned with platelet counts lower than 50K/µL, and that will make me more sensitive to the dose. In clinical practice, I would probably use 5 mg BID in this setting. For patients with a baseline platelet count of 300K/µL that drops to 110K/µL, physicians are frequently concerned that the platelets are on the way to zero and will rapidly stop ruxolitinib. It’s important to note that the platelet count rarely drops to a severely low range, and we have not observed any increase in hemorrhage with ruxolitinib. In this situation, I would simply continue the drug and monitor the patient.

PROF VANNUCCHI: In my experience thrombocytopenia has not been a clinical issue. I have not had any hemorrhagic events occur. I have observed decreases in platelet counts, but I do not remember seeing a patient who had to stop treatment with ruxolitinib because of severe thrombocytopenia. I have adjusted the dose, but I have not stopped treatment. Personalization of dosage is key with this type of agent.

DR GOTLIB: I have a lot of experience with ruxolitinib from being involved in the clinical trials, so I’m not advocating that other physicians do what I do. They should follow the instructions on the package insert. For patients with normal platelet and white blood cell counts, no anemia and normal renal function, I would likely initiate ruxolitinib at 20 mg BID. If the same patient had a platelet count of 130K/µL I would use 15 mg BID. If the patient’s platelet count dropped from 130 to 75K/µL in the first month, then I would likely reduce the dose to 10 mg BID.

It’s not only the level of the platelets that is important but also the pace at which that level declines. If the platelets dropped from 130 to 40K/µL, then I would likely dose reduce to 5 mg BID. Many physicians will conclude that a patient cannot tolerate ruxolitinib if the platelet counts are in the proximity of 40K/µL. In the absence of bleeding, platelet counts would need to be in the 30s before I would consider holding ruxolitinib.

Initially I check platelet counts weekly for 4 to 8 weeks and then every other week. Once I’ve determined that the counts are stable, I check every month and eventually every 3 months if the counts remain stable.