Management

HCL is a rare, indolent B-cell leukemia characterized by "hairy" projections on malignant cells.

• First-Line Therapy: Purine analogues, specifically Cladribine or Pentostatin, are the standard of care and can produce durable remissions.
• Relapsed Disease: Moxetumomab pasudotox-tdfk, an anti-CD22 cytotoxin, is used for patients who have failed at least two prior systemic therapies.

FL is a 60-year-old man who was diagnosed with HCL (Hairy Cell Leukemia). He started cladribine 9 months ago, but unfortunately, his disease relapsed. Which one of the following is considered the preferred regimen for FL's treatment?

• A. Pentostatin
• B. Vemurafenib +/- rituximab
• C. Interferon alfa
• D. Rituximab

Correct Answer: B. Vemurafenib +/- rituximab

Explanation:

FL is a patient with Hairy Cell Leukemia (HCL) who:

• Was treated with cladribine, a purine analog (first-line standard of care).
• Relapsed within 9 months, which is considered early relapse.

Relapsed/Refractory HCL Treatment Strategy:

• First-line relapse options (if relapse occurs after several years):
  • Retreatment with cladribine or pentostatin
  • ± rituximab
• Early relapse or refractory disease (e.g., <2 years, especially <1 year):
  • Suggests purine analog–resistant disease
• Preferred options:
  • BRAF inhibitors (e.g., vemurafenib) if patient is BRAF V600E positive (which occurs in ~90% of HCL)
  • ± Rituximab for synergistic effect

Option Analysis:

• A. Pentostatin: Not preferred in early relapse, especially after prior purine analog use.
• B. Vemurafenib +/- rituximab: Correct. Targeted therapy for relapsed/refractory HCL, especially in BRAF V600E-mutated disease.
• C. Interferon alfa: Obsolete except in pregnancy or unfit patients; low efficacy.
• D. Rituximab alone: Can be used, but not as effective alone as vemurafenib ± rituximab in early relapses.

Key Point: BRAF V600E mutation is present in most classic HCL cases, making vemurafenib a rational and targeted option in relapsed settings.

Final Answer: B. Vemurafenib +/- rituximab