Treatment of Hairy Cell Leukemia
Hairy cell leukemia is highly treatable but rarely cured. Because it is easily controlled, many patients have prolonged survival with the use of sequential therapies. The decision to treat is based on cytopenias (especially if symptomatic), increasing splenomegaly, indications that the disease is progressing, or the presence of other, usually infectious complications. It is reasonable to offer no therapy if the patient is asymptomatic and if blood counts are maintained in an acceptable range. During the COVID-19 (SARS-CoV-2) pandemic, some options for initial standard therapy, including cladribine or pentostatin, have been replaced in favor of other options with less toxicity, but these options also elicit less-durable responses.
Treatment options for hairy cell leukemia include the following:
- Watchful waiting, if feasible.
- Rituximab.
- Vemurafenib (or other BRAF inhibitors) with or without rituximab.
- Recombinant interferon alfa.
- Ibrutinib.
- Moxetumomab pasudotox-tdfk.
- Cladribine with or without rituximab.
- Pentostatin.
- Re-treatment with cladribine or pentostatin.
- Splenectomy.
Rituximab
Rituximab can induce durable complete remissions with minimal toxic effects in patients with multiple relapsing or refractory disease after purine analogue therapy or after treatment with interferon.[1,2,3,4,5][Level of evidence: 3iiiDiv]
Vemurafenib With or Without Rituximab
The BRAF-V600E mutation occurs in almost 100% of patients with classic-form hairy cell leukemia and almost never in patients with other B-cell lymphomas and leukemias, including hairy cell leukemia variants.[6][Level of evidence: 3iiiDiv] Vemurafenib can be given in combination with rituximab.
Evidence (vemurafenib with or without rituximab):
- Three phase II, multicenter studies in the United States and Italy evaluated the BRAF inhibitor vemurafenib, given orally alone for 4 months or orally for 2 months with rituximab infused in eight doses over 18 weeks for patients with relapsed or refractory hairy cell leukemia.[7,8,9]
- After a median follow-up of 23 months, using vemurafenib alone, the overall response rate for 50 patients was 98%, the complete response rate was 38%, and the median treatment-free survival was 25 months and 18 months in the two studies.[7,8][Level of Evidence: 3iiiDiv]
- After a median follow-up of 37 months, for the 30 patients treated with vemurafenib plus rituximab, the complete response rate was 87%. The progression-free survival (PFS) rate was 78% at 37 months, and 65% of patients were cleared of minimal residual disease.[9][Level of Evidence: 3iiiDiv]
Recombinant Interferon Alfa
Recombinant interferon alfa given subcutaneously three times per week for 1 year yields a 10% complete response rate and an 80% overall response rate. The drug frequently produces an influenza-like syndrome early in the course of treatment. Late effects include depression and lethargy. Responding patients who relapse usually react positively to re-treatment with recombinant interferon alfa.[10] Remission can be prolonged with a low-dose maintenance regimen.[11]
Evidence (recombinant interferon alfa):
- A randomized comparison of pentostatin and recombinant interferon alfa demonstrated significantly higher and more durable responses to pentostatin.[12]
Ibrutinib
Evidence (ibrutinib):
- In a phase II study, with a median follow-up of 42 months, 37 patients with refractory hairy cell leukemia had a 54% response rate to ibrutinib, with an estimated 36-month PFS rate of 73% and an overall survival (OS) rate of 85%.[13][Level of evidence: 3iiiDiv]
Moxetumomab Pasudotox-tdfk
Moxetumomab pasudotox-tdfk is an anti-CD22 recombinant immunotoxin that the U.S. Food and Drug Administration approved to treat patients with relapsed or refractory disease.[14,15,16,17]
Evidence (moxetumomab pasudotox-tdfk):
- Moxetumomab pasudotox-tdfk was given to 80 patients who were previously treated with at least two regimens.[18][Level of evidence: 3iiiDiv]
- In a phase II trial, 75% of patients responded and 30% had a complete response.
Cladribine With or Without Rituximab
Cladribine given intravenously by daily subcutaneous injections, or by 2-hour infusions daily for 5 to 7 days results in a complete response rate of 50% to 80% and an overall response rate of 85% to 95%.[19,20,21][Level of evidence: 3iiiDiv] The response rate was lower in 979 patients treated with the Group C mechanism of the National Cancer Institute (i.e., 50% complete remission rate, 37% partial remission rate). Responses are durable with this short course of therapy, and patients who relapse often respond to re-treatment with cladribine.[22,23,24]
Evidence (cladribine with or without rituximab):
- A retrospective review included 83 patients, aged 40 years and younger.[25]
- The median time to first relapse was 54 months for all responders and the median OS was 21 years from diagnosis.
- This drug may cause fever and immunosuppression; documented infection was found in 33% of treated patients.
- In a retrospective study of patients with cladribine-associated neutropenic fever, filgrastim (G-CSF) did not demonstrate a decrease in the percentage of febrile patients, number of febrile days, or frequency of hospital admissions to receive antibiotics.[26] There is a potential increased risk of developing second malignancies with this agent.
- In a phase II study, 68 patients with previously untreated hairy cell leukemia were randomly assigned to receive cladribine 0.15 mg/kg intravenously on days 1 to 5, with eight weekly doses of rituximab concurrently (starting on day 1) or after 6 months if still positive with minimal residual disease (MRD) testing.[27]
- With a median follow-up of 96 months, 94% of patients who received concurrent therapy were MRD-free, compared with 12% of patients who received delayed therapy.[27][Level of evidence: 3iiiDiv]
- Concurrent therapy resulted in more need for platelet transfusions, but also higher neutrophil and platelet counts after 1 month.
MRD testing in this setting has never been validated as a clinically significant end point. This concept requires further study, but hairy cell leukemia is rare, with only 600 to 800 new cases annually in the United States.
Pentostatin
Pentostatin given intravenously every other week for 3 to 6 months produces a 50% to 76% complete response rate and an 80% to 87% overall response rate.[12,28] Complete remissions are of substantial duration.
Evidence (pentostatin):
- In two trials with 9-year median follow-ups, relapse-free survival rates ranged from 56% to 67%.[29,30]
- Side effects included fever, immunosuppression, cytopenias, and renal dysfunction.
- A randomized comparison of pentostatin and recombinant interferon alpha-2a demonstrated higher and more durable responses to pentostatin.[12]
Re-treatment With Cladribine or Pentostatin
Patients with hairy cell leukemia who relapse after the first course of cladribine or pentostatin often respond well to re-treatment with the same or another purine analogue, especially if relapse occurs after 2 years.[24,28,31,32,33,34][Level of evidence: 3iiiDiv]
Splenectomy
Splenectomy will partially or completely normalize the peripheral blood in most patients with hairy cell leukemia.[35] Usually little or no change occurs in the bone marrow after splenectomy, and virtually all patients have progressive disease within 12 to 18 months. Therefore, because a number of more effective alternatives are available, splenectomy plays a decreasing role in the treatment of this disease.
Current Clinical Trials
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
References:
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- Kreitman RJ, Tallman MS, Robak T, et al.: Minimal residual hairy cell leukemia eradication with moxetumomab pasudotox: phase 1 results and long-term follow-up. Blood 131 (21): 2331-2334, 2018.
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- Kreitman RJ, Tallman MS, Robak T, et al.: Phase I trial of anti-CD22 recombinant immunotoxin moxetumomab pasudotox (CAT-8015 or HA22) in patients with hairy cell leukemia. J Clin Oncol 30 (15): 1822-8, 2012.
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