With respect to the patient who develops anemia while on therapy, if you’re starting at a high dose or a dose perhaps higher than is recommended by the prescribing information, you may want to hold and lower the dose, or you may want to try to ride through the anemia. We know that hemoglobin does dip down, but then it improves over 8 to 12 weeks — perhaps not in every patient, but it does tend to improve and get near or back to baseline. I believe for the most part, patients are able to ride through the anemia and either maintain a dose or receive a lower dose with attempted dose escalation over time. I believe the message is: Barring someone having horrible new transfusion-dependent anemia that doesn’t respond to dose reduction, you can probably either maintain the dose or dose reduce slightly to get the other benefits of ruxolitinib therapy.

For all my patients who are symptomatic I will use ruxolitinib. The patient’s symptom status rather than the disease stage drives my decision. If a patient is complaining about symptoms, they need therapy. I don’t usually dose modify based on anemia or transfusion requirements unless the hemoglobin level drops from 11 to 6 g/dL. However, I will consider the patient’s age. For a patient aged 40 to 45 years, I would treat aggressively. However, if the patient is 70 years old, I would be more careful. If the platelet counts are normal, I will dose reduce to 10 or 15 mg BID.

I don’t change my initial starting dose of ruxolitinib based on either the presence of anemia or the need for transfusion. Physicians and patients need to give the anemia several months to resolve, and that’s important for them to know. Otherwise, patients will come right off of therapy and they won’t continue on it. That’s a problem.

It’s difficult to explain to a patient who’s not transfusion dependent or who is transfusion naïve that I’m going to put them on a drug to make them feel better, but in the course of that their hemoglobin levels will drop. I explain to patients that therapy-related anemia is different than anemia directly related to the disease and it is not a negative prognostic indicator. I spend a lot of time counseling patients up front to expect anemia and to not be thrown off by it. I would say that the majority of patients to whom I administer ruxolitinib, around 70% to 75%, will develop some degree of anemia, which usually occurs within the first 3 months of treatment. The hemoglobin level does plateau and improves over the subsequent several months.

Initially I’ll hold the same dose and perform a transfusion. However, I would consider holding therapy or changing to a different therapy if, for example, the patient has a sudden and profound drop in hemoglobin levels and is symptomatic and requiring transfusions. That would make me pause. Another scenario would be if a patient has been on therapy for 6 to 8 months and is requiring transfusions every 2 weeks and I am not impressed with their spleen reduction or symptom improvement. I would reconsider treating them continuously with ruxolitinib.

I would say that, in practice, anemia is probably the largest issue in terms of ruxolitinib use. Hemoglobin level is the largest driver of how we initially dose ruxolitinib. The natural cutoffs would be hemoglobin levels of 10 g/dL and higher, hemoglobin levels of 8 to 10 g/dL and patients who are transfusion dependent. For patients who are not anemic, the highest dose of ruxolitinib that I would start at is 15 mg BID. For patients with a hemoglobin level of less than 10 mg/dL, I would administer 10 mg BID of ruxolitinib. If a patient is transfusion dependent, we typically start at 5 mg BID and increase the dose.

I tend to make the decision about the starting dose and ride it out for the first 3 months. Jumping around with dose in terms of dose reductions in the first several weeks is probably not ideal. I think anemia is a somewhat known, expected and sometimes mildly transient toxicity associated with ruxolitinib. If I've made the commitment to try the medication for the patient’s benefit, I don’t try to dose adjust in the first few weeks just because of anemia.

If I have a patient who develops anemia in the first 8 to 12 weeks of 10-mg BID ruxolitinib, I would not change their therapy and I would hold the course. In this scenario, I would look for other causes of blood loss and make sure the patient is folate replete. I would want to rule out important issues such as hemolysis, infection and abnormal kidney function that could cause a patient to become anemic. If I can’t find a source for the blood loss or blood destruction, then I will continue with ruxolitinib therapy.

The fact that ruxolitinib therapy will lower hemoglobin levels early on is published. Eventually hemoglobin levels tend to normalize. Patients need to be closely monitored over time. If there is no blood loss or destruction and the patient is feeling better, I will not stop treatment. I don’t want to stop treatment because stopping ruxolitinib therapy may lead to a rebound of the patient’s disease. I don’t mind administering a blood transfusion because the hemoglobin levels of many patients will come back to where they started out.

As long as the patient is responding to treatment, I would continue ruxolitinib. I would treat at 10 mg BID and hold, taking my time without reacting because this is a good and safe dose.

Drops in hemoglobin levels on ruxolitinib are common. At least 30% to 40% of patients experience a drop of 1 g/dL or more. For a patient who has never been anemic but whose hemoglobin level falls from 12 g/dL to about 8.5 g/dL within 4 to 6 weeks of ruxolitinib initiation, I would continue therapy for a bit longer and dose reduce if the patient is continuing to benefit from ruxolitinib. However, I am often reluctant to dose reduce just for anemia.

As long as the patient doesn’t have life-threatening thrombocytopenia or neutropenia, I will continue treatment with the same dose of ruxolitinib, with the assumption that we are aware of the anemia. We know that we have to give it a few months to see if it gets better. If it doesn’t get better at the end of 4 to 5 months, we have to decide whether we want to continue with ruxolitinib therapy. The physician has to make a decision based on whether the patient experienced improvements in anemia and other disease- and treatment-related symptoms.

When you administer ruxolitinib at the recommended dose, about a quarter of patients will develop significant anemia. Proactive monitoring over the first couple of months when anemia is known to occur and avoiding treatment interruptions are important because maintaining the exposure to ruxolitinib is ideal. If you stop treatment, the symptoms come back within 10 days. If you see patients only once a month, the patient can develop significant myelosuppression. At that point the physician may say, “Oh. Now he’s too low. We’ll stop ruxolitinib.” As such, all the benefits will be lost.

The better way would be to decrease the dose and administer a transfusion. Another transfusion may be needed in 2 weeks, but then the red blood cell count will have rebounded because you lowered the ruxolitinib dose and the benefit is not lost. For example, for a patient with a hemoglobin level of about 10 g/dL and a platelet count of 220K/µL who is started on 20 mg BID of ruxolitinib but develops anemia after 2 weeks of therapy, I would dose reduce to 10 mg BID and perform a blood transfusion. A proactive decrease and acceptance of occasional transfusions while patients are recovering at the lower dose are desirable because of the rebound in the red blood cell count.