Anemia can be a challenge but usually does not preclude successful treatment

Anemia can be a challenge but usually does not preclude successful treatment

John O Mascarenhas, MD

DR MASCARENHAS: It is important that patients who are transfusion independent at baseline and their family members understand that, although ruxolitinib effectively addresses symptoms and reduces spleen size, it can cause anemia. This is usually predictable and occurs within 3 months. One needs to weigh the quality-of-life aspect of blood transfusions against symptom improvement. For most patients the odds are in favor of remaining on the drug, especially after they start ruxolitinib and are feeling better.

I don’t change my initial starting dose of ruxolitinib on the basis of either the presence of anemia or the need for transfusion. Physicians and patients need to allow the anemia several months to resolve, and that’s important for them to know. Otherwise patients will come right off 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 administer a drug to make them feel better but in the course of that improvement their hemoglobin levels will drop. I explain to patients that therapy-related anemia is different from anemia directly related to the disease and that it is not a negative prognostic indicator. I spend a lot of time counseling patients up front to expect anemia and not to be discouraged 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 reaches a plateau and improves during the subsequent several months.

Initially I’ll maintain the same dose and perform a transfusion. However, I would consider holding therapy or changing to a different therapy if, for example, the patient had a sudden and profound drop in hemoglobin level and was symptomatic and requiring transfusions. That would make me pause. Another scenario would be if a patient had been receiving therapy for 6 to 8 months and was requiring transfusions every 2 weeks and I was not impressed with the spleen reduction or symptom improvement. I would reconsider continuous treatment with ruxolitinib.

Alessandro M Vannucchi, MD

PROF VANNUCCHI: Sometimes we say we are not treating the disease but rather the clinical symptoms associated with it. The most commonly asked questions are, should ruxolitinib treatment be initiated for patients with anemia or thrombocytopenia, how should anemia be managed and what dose of ruxolitinib is appropriate for patients with anemia?

Therapy for myelofibrosis is clearly individualized. This is a disease for which it is difficult to think of a common dose as exists with imatinib in the case of chronic myelogenous leukemia. Ruxolitinib is a therapy that you must adapt to suit the individual patient.

Anemia, in my experience, is more of a black-and-white issue because some patients will never agree to transfusion. A patient’s hemoglobin may drop from 11 to 6 g/dL, for example, and then that patient will need transfusion, possibly for several months. Some of these patients want to continue ruxolitinib because they are feeling better from all other symptoms of their disease, but some patients want to stop treatment because they do not want to continue to undergo transfusions.

Elias Jabbour, MD

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

David P Steensma, MD

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

Jerry L Spivak, MD

DR SPIVAK: If I had a patient who developed anemia in the first 8 to 12 weeks of ruxolitinib at 10 mg BID, I would not change the therapy and I would hold the course. In this scenario I would seek other causes of blood loss and make sure the patient was 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 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. If no blood loss or destruction occurs 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 the level at which they started.

As long as the patient was 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.

Moshe Talpaz, MD

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