The starting dose of ruxolitinib depends on the baseline platelet count. For the patient with a platelet count of 70,000 I would initiate ruxolitinib at 5 mg BID. For the patient with a platelet count of 35,000 I would start ruxolitinib at 5 mg QD.

After initiating ruxolitinib I draw blood weekly for 6 to 8 weeks. Thereafter I check every other week and then once per month after I see that the dynamic of the hemoglobin and the platelet numbers are status quo.

I have progressively moved away from starting ruxolitinib at 15 mg BID unless the patient comes in with a platelet count of something like 600K/µL. I’ve adopted a “start low and titrate up” approach. I’m on the verge of publishing recommendations for dosing ruxolitinib based on my own experience and the available data. I’ve had too many problems, especially lately, with patients who start with robust platelet counts but then run into trouble and I have to dose reduce in the middle of the month. My recommendation now is to start at 10 mg BID and go up. If the patient’s platelet count is 100K/µL or less, I start at 5 mg BID and go up slowly.

I do not typically recommend that community oncologists use ruxolitinib in patients with platelet counts below 50K/µL. I have only 1 patient with 33 to 34K/µL platelets and intractable itching who I am treating with ruxolitinib 5 mg QD.

I am most concerned with platelet counts less 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.

Some platelet drops after initiating ruxolitinib lead to dose discontinuations that probably aren’t appropriate. For a patient with a baseline platelet count of 300K/µL that drops to 110K/µL, physicians will frequently be concerned that the platelets are on their way to zero and rapidly stop ruxolitinib. It’s important to note that the platelet count rarely drops to severely low ranges, and we have not observed any increase in hemorrhage with ruxolitinib. In this situation, I would simply continue the drug and monitor the patient.

Typically, I start patients on 10 mg BID, even if their platelet count is less than 50K/µL.

I follow the package insert with respect to dosing ruxolitinib based on platelet counts. One of the challenges we face with recommendations in a package insert is whether or not that’s reality. We’re somewhat obliged to follow those recommendations or justify why we’re not doing so. From the dose-finding study in 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 drop the dose below that — unless it’s due to poor renal clearance — the effectiveness of ruxolitinib is just not as good. That’s supported by the study that Moshe Talpaz presented at ASH 2012.

Both the COMFORT-I and the COMFORT-II study were open to patients with 100K/µL or more platelets. It was not initially open to patients with lower platelet counts because it was a safety issue.

I presented a study at ASH 2012 that started at a dose of 5 mg BID of ruxolitinib and allowed escalation in all patients based on platelet counts at monthly intervals. We included patients with platelet counts between 50 and 100K/µL, which means moderate (50 to 75K/µL platelets) and mild (75 to 100K/µL platelets) thrombocytopenia. The take-home message from the study was that the vast majority of patients can receive treatment if they have platelets at the starting point of that range between 50 and 100K/µL, and the average patient ended up receiving 10 mg BID.

The responses were slightly lower than the ones seen in COMFORT-I and II but not dramatically lower. About 35% of the patients still had a reduction in spleen volume to a level of partial response, and about 40% of the patients had 50% or more reduction in symptoms. Another benefit was much less prominent anemia. The anemia seemed to have been nullified by this different approach of gradual escalation, and it seems that that may be an approach that will be adopted increasingly by physicians.

I have administered ruxolitinib to patients with platelet counts less than 50K/µL. However, the concern is that most of these patients already have damaged bone marrow. They have low cellularity and heavy fibrosis, and the platelet counts continue to drop. So I suggest checking the bone marrow and the cellularity first and being careful not to administer a myelosuppressive treatment to patients with an extremely low cellularity of 10% to 20%. It will not be beneficial.