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Indicators Prompting Treatment of HCL

Panelists: Farhad Ravandi-Kashani, MD, The University of Texas MD Anderson Cancer Center; Robert J. Kreitman, MD, National Institutes of Health
Published: Friday, Jul 12, 2019



Transcript:

Farhad Ravandi-Kashani, MD: What are the indicators that prompt you to start treatment?

Robert J. Kreitman, MD: In our experience, we use the same indicators of treatment. We require cytopenias, which include the 1, 10, and 100 rule: the ANC [absolute neutrophil count] less than 1; hemoglobin less than 10 g/dL, although that’s very similar to 11; and platelet count less than 100 per mm3. We also use lymph nodes greater than 2 cm, enlarging. We also use painful splenomegaly as an indicator, and frequent infections. We used to use, and in some protocols we still use an increasing lymphocytosis of malignant cells, particularly over 5000 malignant cells. This is particularly important for patients who might have a hairy cell leukemia variant or have had a splenectomy, in which these patients are less likely to develop indications for treatment. But once they need treatment, they’re much more advanced because a splenectomy or hairy cell variant tends to be less associated with these low blood counts, unless they’re very far advanced. For that reason, for some of our protocols, we sometimes include a lymphocytosis of at least 5000 of malignant cells. But that’s not universally used.

Farhad Ravandi-Kashani, MD: I know that many of your patients are enrolled in clinical trials. If you go by NCCN [National Comprehensive Cancer Network] Guidelines, use of clinical trials is still considered very important. But in terms of first-line therapy, single-agent cladribine or monotherapy with pentostatin, it remains the standard. Is there anything in your practice that makes you decide between either of these 2 drugs?

Robert J. Kreitman, MD: Yeah. So in most cases, we use cladribine, and I think that’s the case across the country and the world. That’s because cladribine can be given in a single 5-day or 7-day course. Whereas pentostatin is given every other week for 3 to 6 weeks and sometimes a longer number of months. Because of the convenience of the cladribine regimen and the fact that the toxicity is usually well handled by patients, cladribine tends to be the most common.

Pentostatin tends to be advantageous in a patient who’s quite ill, and you’re not sure whether they can make it through an aggressive course of chemotherapy. In these patients, you can use a reduced dose of pentostatin. Instead of using the 4 mg/m2 dose, you can use 2 mg/m2 dose or 3 mg/m2. Then after 2 weeks for the next dose, their counts might be better. If not, they might be better for the third dose, and then they can dose escalate back up to the standard 4 mg/m2 dose. That tends to be a safe way to deliver first-line purine analog in some patients with very poor blood counts or very high risk. We rarely use that, but that is used in many places, and I think it does have some advantages. I’ve actually recommended that in some patients who are quite ill—elderly, etc—and I’ve seen it work.

Farhad Ravandi-Kashani, MD: I think perhaps with highly exceptional cases, interferon alfa is no longer used for treating hairy cell leukemia. What are your thoughts on that?

Robert J. Kreitman, MD: I agree with that. I think that it probably does have some benefit, but that benefit is also seen in the non-myelotoxic alternatives like BRAF inhibitors that most patients are eligible for. These days, if patients need something that’s not chemotherapy to improve their counts, before getting a drug like cladribine or pentostatin, we often will use a BRAF inhibitor to do that. Interferon also has some toxicities, including low platelets and low neutrophils, so it’s not exactly a non-myelotoxic drug. But that was its use, and I think nowadays with the BRAF inhibitors, it does have less use.

Transcript Edited for Clarity

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Transcript:

Farhad Ravandi-Kashani, MD: What are the indicators that prompt you to start treatment?

Robert J. Kreitman, MD: In our experience, we use the same indicators of treatment. We require cytopenias, which include the 1, 10, and 100 rule: the ANC [absolute neutrophil count] less than 1; hemoglobin less than 10 g/dL, although that’s very similar to 11; and platelet count less than 100 per mm3. We also use lymph nodes greater than 2 cm, enlarging. We also use painful splenomegaly as an indicator, and frequent infections. We used to use, and in some protocols we still use an increasing lymphocytosis of malignant cells, particularly over 5000 malignant cells. This is particularly important for patients who might have a hairy cell leukemia variant or have had a splenectomy, in which these patients are less likely to develop indications for treatment. But once they need treatment, they’re much more advanced because a splenectomy or hairy cell variant tends to be less associated with these low blood counts, unless they’re very far advanced. For that reason, for some of our protocols, we sometimes include a lymphocytosis of at least 5000 of malignant cells. But that’s not universally used.

Farhad Ravandi-Kashani, MD: I know that many of your patients are enrolled in clinical trials. If you go by NCCN [National Comprehensive Cancer Network] Guidelines, use of clinical trials is still considered very important. But in terms of first-line therapy, single-agent cladribine or monotherapy with pentostatin, it remains the standard. Is there anything in your practice that makes you decide between either of these 2 drugs?

Robert J. Kreitman, MD: Yeah. So in most cases, we use cladribine, and I think that’s the case across the country and the world. That’s because cladribine can be given in a single 5-day or 7-day course. Whereas pentostatin is given every other week for 3 to 6 weeks and sometimes a longer number of months. Because of the convenience of the cladribine regimen and the fact that the toxicity is usually well handled by patients, cladribine tends to be the most common.

Pentostatin tends to be advantageous in a patient who’s quite ill, and you’re not sure whether they can make it through an aggressive course of chemotherapy. In these patients, you can use a reduced dose of pentostatin. Instead of using the 4 mg/m2 dose, you can use 2 mg/m2 dose or 3 mg/m2. Then after 2 weeks for the next dose, their counts might be better. If not, they might be better for the third dose, and then they can dose escalate back up to the standard 4 mg/m2 dose. That tends to be a safe way to deliver first-line purine analog in some patients with very poor blood counts or very high risk. We rarely use that, but that is used in many places, and I think it does have some advantages. I’ve actually recommended that in some patients who are quite ill—elderly, etc—and I’ve seen it work.

Farhad Ravandi-Kashani, MD: I think perhaps with highly exceptional cases, interferon alfa is no longer used for treating hairy cell leukemia. What are your thoughts on that?

Robert J. Kreitman, MD: I agree with that. I think that it probably does have some benefit, but that benefit is also seen in the non-myelotoxic alternatives like BRAF inhibitors that most patients are eligible for. These days, if patients need something that’s not chemotherapy to improve their counts, before getting a drug like cladribine or pentostatin, we often will use a BRAF inhibitor to do that. Interferon also has some toxicities, including low platelets and low neutrophils, so it’s not exactly a non-myelotoxic drug. But that was its use, and I think nowadays with the BRAF inhibitors, it does have less use.

Transcript Edited for Clarity
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