What is an immunomodulating agent used to treat hairy cell leukemia?

From the Guidelines

Cladribine is the most effective immunomodulating agent for treating hairy cell leukemia, with a complete remission rate of approximately 80-90%. This medication is a purine analog that works by interfering with DNA synthesis in rapidly dividing cells, particularly targeting lymphocytes 1. For hairy cell leukemia, cladribine is typically administered as a single course of 0.09-0.1 mg/kg/day by continuous intravenous infusion for 7 days. This regimen often results in complete remission in approximately 80-90% of patients, with many experiencing long-lasting responses. Cladribine selectively accumulates in lymphocytes with high deoxycytidine kinase activity, causing DNA damage and triggering apoptosis in these cells 1. This mechanism makes it particularly effective against the abnormal B-lymphocytes characteristic of hairy cell leukemia.

Some key points to consider when using cladribine include:

• The potential for bone marrow suppression, infections, and fever, which require careful monitoring 1
• The importance of administering treatment in a hospital setting under the supervision of a hematologist-oncologist experienced in managing leukemia 1
• The possibility of using alternative schedules, such as weekly infusion or reduced-dose subcutaneous administration, which may have similar efficacy and safety profiles 1
• The potential benefits of combining cladribine with other agents, such as rituximab, which may improve complete remission rates and failure-free survival 1

However, it's also important to note that BRAF inhibitors, such as vemurafenib, may be considered as an alternative treatment option, particularly in patients with active infection or those at high risk of SARS-CoV-2 infection 1. These agents have been shown to induce rapid responses without myelosuppression and may be used as bridging therapy until a more definitive treatment can be administered. Nevertheless, cladribine remains the most established and effective treatment for hairy cell leukemia, and its use should be prioritized in most cases 1.

From the FDA Drug Label

INDICATIONS AND USAGE Cladribine Injection, USP is indicated for the treatment of active Hairy Cell Leukemia as defined by clinically significant anemia, neutropenia, thrombocytopenia or disease-related symptoms. INDICATIONS AND USAGE NIPENT is indicated as single-agent treatment for both untreated and alpha-interferon-refractory hairy cell leukemia patients with active disease as defined by clinically significant anemia, neutropenia, thrombocytopenia, or disease-related symptoms.

Immunomodulating agents used to treat hairy cell leukemia include:

• Cladribine (IV) 2
• Pentostatin (IV) 3

These agents are used to treat hairy cell leukemia with active disease.

From the Research

Immunomodulating Agents for Hairy Cell Leukemia

• Cladribine is an immunomodulating agent used to treat hairy cell leukemia, as evidenced by its ability to inhibit repair of single-strand DNA breaks in certain malignant lymphocyte and monocyte subtypes 4.
• The efficacy of cladribine in treating hairy cell leukemia has been demonstrated in several studies, with complete response rates ranging from 76% to 91% 4, 5.
• Cladribine has also been shown to be effective in treating hairy cell leukemia-variant, with an overall response rate of 75% 5.
• The combination of cladribine with other agents, such as rituximab, has been explored as a potential treatment option for recurrent or refractory hairy cell leukemia, with promising results 6, 7.
• Cladribine has emerged as the preferred initial therapy for hairy cell leukemia, with durable complete remissions and the ability to be successfully retreated in patients who relapse 8.

Treatment Outcomes

• The response rate to cladribine in hairy cell leukemia patients has been reported to be as high as 90%, with complete hematologic responses achieved in 71% of patients 7.
• The combination of cladribine with rituximab has been shown to yield a 100% response rate, even in patients who have received prior treatment 7.
• However, when rituximab is used as monotherapy, the response rate is lower, and the relapse rate is a concern 7.

Future Directions

• Further studies are needed to confirm the superiority of the combination rituximab + cladribine over cladribine alone, both as frontline therapy and at relapse 7.
• The role of cladribine in the treatment of hairy cell leukemia continues to evolve, with ongoing research exploring its use in combination with other agents and its potential as a retreatment option for patients who relapse 6, 8.