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Cytopenia-Related Considerations in Myelofibrosis

Insights From: Srdan Verstovsek, MD, PhD, University of Texas MD Anderson Cancer Center; Daniel J. DeAngelo, MD, PhD, Dana-Farber Cancer Institute; Kim-Hien T. Dao, DO, PhD, Oregon Health & Science University
Published: Friday, Dec 02, 2016


Transcript:

Kim-Hien T. Dao, DO, PhD:
For patients who have anemia with myelofibrosis, you have to carefully make sure you follow their trends over time. For someone who suddenly has a low hemoglobin, then you have to be thinking of things that could cause a sudden drop in their hemoglobin, such as blood loss anemia, development of iron deficiency, and also acute myeloid leukemia or myelodysplasia development. So, one has to consider the trajectory and trend of the low hemoglobin. Whether it’s occurring gradually over time or suddenly, they have a different workup and monitoring plan associated with that.

For those who are progressively developing low hemoglobin over time, that may indicate that their marrow function is starting to fail, and their myelofibrosis is uncontrolled and progressing. So, in those patients, we might have to consider treatment that would potentially improve the marrow function, or the erythropoiesis, and myelofibrosis, and there are agents to do that. So, for example, we can use androgens or danazol as adjunctive therapy. We can use growth factors in select patients. We could also use immunomodulators, such as thalidomide and lenalidomide. Although their response rates are not spectacular, it is worth a try in some patients who develop anemia with myelofibrosis.

Ruxolitinib does initially reduce hemoglobin, so that is something we have to counsel our patients very carefully on. But, over time, we see that their hemoglobin recovers to baseline, and in some cases improve above baseline. So, that is also a consideration. Anemia has to be very carefully evaluated, but some of the therapies that we can offer will improve the anemia to some degree.

Daniel J. DeAngelo, MD, PhD: Anemia is a very common hematologic abnormality in patients with myelofibrosis, and the development of progressive anemia as part of the dynamic scoring system has been used as an indication of progression of the disease. Unfortunately, there are limited ways of addressing the anemia issue. Growth factors, although used—I use them in my clinical practice—are seldom effective. But in those patients, they can be. It’s important to measure an erythropoietin level at baseline before initiating growth factor support. Transfusions are obviously the mainstay.

For patients with a 5q abnormality—rare in patients with chronic myelofibrosis—the IMiDs, thalidomide or lenalidomide, can be used to augment or improve the anemia. When a patient has progressed to splenomegaly and symptoms without a 5q abnormality, we usually initiate JAK2 inhibitors. One of the side effects of JAK2 inhibition is the development of progressive anemia. And this is an on-target effect. A lot of patients and physicians will use this as saying, “Well, this therapy is not effective.” But, you need to remember that JAK2 is a required pathway for the development of erythropoiesis or red cell production. And by inhibiting JAK2, you do have a disease-modifying therapy in terms of the myelofibrosis, but it will worsen the anemia. It’s not a sign of disease progression, but one that needs to be treated aggressively with red cell transfusions and growth factor support where appropriate.

Kim-Hien T. Dao, DO, PhD: Thrombocytopenia, or low platelets, can occur in patients with myelofibrosis, and the provider should monitor the trends very carefully because some patients can have very low platelets. And so, when a patient develops low platelets—and this has been a trend that’s been ongoing—it may be an indicator that their disease is progressing or maybe there’s sequestration from their splenomegaly. In patients with platelets that are above a safe range, 50,000 per mm3 for example, often that doesn’t warrant treatment as long as it’s in a safe range. And that safe range can vary between patients depending on whether they’re required to be on anticoagulation or not, or if they’ve had bleeding issue. So, it is an individualized decision whether we treat patients based on low platelets, but this is something that would trigger, certainly, more careful monitoring.

Transcript Edited for Clarity
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Transcript:

Kim-Hien T. Dao, DO, PhD:
For patients who have anemia with myelofibrosis, you have to carefully make sure you follow their trends over time. For someone who suddenly has a low hemoglobin, then you have to be thinking of things that could cause a sudden drop in their hemoglobin, such as blood loss anemia, development of iron deficiency, and also acute myeloid leukemia or myelodysplasia development. So, one has to consider the trajectory and trend of the low hemoglobin. Whether it’s occurring gradually over time or suddenly, they have a different workup and monitoring plan associated with that.

For those who are progressively developing low hemoglobin over time, that may indicate that their marrow function is starting to fail, and their myelofibrosis is uncontrolled and progressing. So, in those patients, we might have to consider treatment that would potentially improve the marrow function, or the erythropoiesis, and myelofibrosis, and there are agents to do that. So, for example, we can use androgens or danazol as adjunctive therapy. We can use growth factors in select patients. We could also use immunomodulators, such as thalidomide and lenalidomide. Although their response rates are not spectacular, it is worth a try in some patients who develop anemia with myelofibrosis.

Ruxolitinib does initially reduce hemoglobin, so that is something we have to counsel our patients very carefully on. But, over time, we see that their hemoglobin recovers to baseline, and in some cases improve above baseline. So, that is also a consideration. Anemia has to be very carefully evaluated, but some of the therapies that we can offer will improve the anemia to some degree.

Daniel J. DeAngelo, MD, PhD: Anemia is a very common hematologic abnormality in patients with myelofibrosis, and the development of progressive anemia as part of the dynamic scoring system has been used as an indication of progression of the disease. Unfortunately, there are limited ways of addressing the anemia issue. Growth factors, although used—I use them in my clinical practice—are seldom effective. But in those patients, they can be. It’s important to measure an erythropoietin level at baseline before initiating growth factor support. Transfusions are obviously the mainstay.

For patients with a 5q abnormality—rare in patients with chronic myelofibrosis—the IMiDs, thalidomide or lenalidomide, can be used to augment or improve the anemia. When a patient has progressed to splenomegaly and symptoms without a 5q abnormality, we usually initiate JAK2 inhibitors. One of the side effects of JAK2 inhibition is the development of progressive anemia. And this is an on-target effect. A lot of patients and physicians will use this as saying, “Well, this therapy is not effective.” But, you need to remember that JAK2 is a required pathway for the development of erythropoiesis or red cell production. And by inhibiting JAK2, you do have a disease-modifying therapy in terms of the myelofibrosis, but it will worsen the anemia. It’s not a sign of disease progression, but one that needs to be treated aggressively with red cell transfusions and growth factor support where appropriate.

Kim-Hien T. Dao, DO, PhD: Thrombocytopenia, or low platelets, can occur in patients with myelofibrosis, and the provider should monitor the trends very carefully because some patients can have very low platelets. And so, when a patient develops low platelets—and this has been a trend that’s been ongoing—it may be an indicator that their disease is progressing or maybe there’s sequestration from their splenomegaly. In patients with platelets that are above a safe range, 50,000 per mm3 for example, often that doesn’t warrant treatment as long as it’s in a safe range. And that safe range can vary between patients depending on whether they’re required to be on anticoagulation or not, or if they’ve had bleeding issue. So, it is an individualized decision whether we treat patients based on low platelets, but this is something that would trigger, certainly, more careful monitoring.

Transcript Edited for Clarity
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