Hairy Cell Leukemia Treatment Protocols

Treatment protocols for hairy cell leukemia (HCL) are provided below, including those for initial treatment, resistant disease, variant HCL, and relapsed/refractory HCL. ^{[1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13]}

Symptoms requiring initiation of treatment

Many patients with classic HCL appear to be asymptomatic even after diagnosis, and about 10% will never require therapy. ^[14] Treatment should be initiated if the patient develops 1 or more of the following signs and symptoms:

• Abdominal fullness or discomfort due to splenomegaly

• Complaints of fatigue, weakness, and weight loss

• Platelet count < 100,000/μL

• Recurrent infections, which may be life-threatening, secondary to granulocytopenia and monocytopenia (absolute neutrophil count <  1000/µL; see the Absolute Neutrophil Count calculator)

• Symptomatic anemia with a hemoglobin concentration < 11.0 g/dL

• Vasculitis (rare)

Initial treatment recommendations

The purine analogues cladribine and pentostatin are first-line agents in the treatment of HCL. Cladribine is more commonly used because of ease of administration. ^[15]

• Cladribine 0.09 mg/kg/day by continuous IV infusion for 7d (FDA approved) or  0.14 mg/kg/day IV over 2h or SC for 5d; 5-6 weekly doses of 0.14 mg/kg have also been studied ^[5] (cost, inconvenience, and adverse reactions less likely with SC; can use growth factors if febrile neutropenia develops) or

• Pentostatin 4 mg/m² IV bolus or over 30min every 2wk with 1.5 L of hydration for each dose for 3-6mo or

• Interferon alfa 2b 2 million U/m² SC 3 times per week for 12-18mo for relapsed or refractory HCL

• Splenectomy (laparoscopic preferred) is considered for patients with bleeding from severe thrombocytopenia or failure to respond to systemic therapy; administer pneumococcal, meningococcal, and Haemophilusinfluenzae vaccines prior to surgery

Updated guidelines from the Hairy Cell Leukemia Foundation (HCLF) note that because treatment with a purine analogue–based regimen may be associated with prolonged granulocytopenia, which increases risk for a severe course of COVID-19, off-label treatment may be considered in patients with HCL who have pancytopenia and an active uncontrolled infection. ^[18] In conjunction with appropriate antibiotics or antifungal or antiviral agents, the HCLF suggests the following:

• A BRAF inhibitor (eg, vemurafenib), in patients with classic HCL that harbors a BRAF V600E
• The combination of a BRAF inhibitor with either a monoclonal anti-CD20 antibody (eg, rituximab) or a MEK inhibitor (eg, trametinib) can further increase the rate of durable remissions without inducing severe myelosuppression

Variant hairy cell leukemia

Variant hairy cell leukemia is resistant to the standard treatments, which include the use of purine analogues and interferon alfa. Combinations of rituximab and purine analogs are under evaluation. ^[14]

Relapsed/refractory disease

Patients may relapse after initial treatment, so it is important to administer a second cycle of treatment as that can lead to another remission.

Although pentostatin and cladribine provide responses in greater than 85% of patients, and a median progression-free survival of up to 15 years, alternative treatments (eg, the addition of rituximab ^[15] ) are needed for patients whose disease becomes refractory to these treatments.

Moxetumomab pasudotox

Moxetumomab pasudotox is an anti-CD22 recombinant immunotoxin indicated for adults with relapsed or refractory hairy cell leukemia (HCL) who have received at least 2 prior systemic therapies, including a purine nucleoside analog. ^[16]

Dose: 0.04 mg/kg IV on days 1, 3, and 5 of each 28-day cycle; infuse over 30 minutes; continue for maximum of 6 cycles or until disease progression or unacceptable toxicity occurs.

Drugs that are being evaluated in clinical trials include ibrutinib (first class oral inhibitor of Bruton kinase) and BRAF V600E inhibitors as the majority of classic HCL harbors the BRAF mutation. ^[17]