Hairy cell leukemia treatment strategies: A real-world multicenter experience Free

Background

Hairy cell leukemia (HCL) is a rare, indolent B-cell malignancy accounting for ~1% of all lymphoid neoplasms. While purine analogs remain the standard first-line therapy, the increasing use of combination regimens and targeted agents has expanded the therapeutic landscape. Data on long-term outcomes in real-world practice remain limited.

Methods

This is a retrospective, multicenter cohort study. We included 104 patients aged ≥18 years with a diagnosis of HCL who had at least one oncology visit from January 1, 2010, to July 17, 2025. Patients diagnosed prior to 2010 were left-truncated to account for survivorship bias. Data were abstracted from electronic medical records. Key outcomes included treatment patterns, response rates, overall survival (OS), and progression-free survival (PFS).

Results

The median age at diagnosis was 56.9 years (range 32.1–83.8), and 80% were male. Most patients (77%) were diagnosed during or after 2010. The most frequent frontline therapies were cladribine (63%), cladribine with rituximab (12%), rituximab monotherapy (9.7%), vemurafenib-based regimens (7.7%), splenectomy with or without interferon (3.8%), interferon monotherapy (2.9%), and other (1.9%). The overall complete response (CR) rate to first-line therapy was 63%, with 15% achieving a partial response (PR) and 22% having stable or no response. For patients receiving cladribine with rituximab first-line (n = 12), 92% had a CR. For patients receiving cladribine monotherapy first-line (n = 65), 63% had a CR and 12% had a PR. For patients receiving rituximab monotherapy first-line (n = 10), 50% had a CR and 20% had a PR. For patients receiving vemurafenib-based regimens first-line (n = 8), 75% had a CR.

Among the 39 patients who received second-line therapy, the most common regimens included cladribine (31%), rituximab (26%), cladribine plus rituximab (18%), and vemurafenib-based regimens (13%). The CR rate after second-line therapy was 72%. For patients receiving cladribine with rituximab second-line (n = 7), 86% had a CR and 14% had a PR. For patients receiving cladribine monotherapy second-line (n = 12), 67% had a CR. For patients receiving rituximab monotherapy second-line (n = 10), 80% had a CR and 10% had a PR. For patients receiving vemurafenib-based regimens second-line (n = 5), 40% had a CR and 20% had a PR.

Among the 17 patients who received third-line therapy, the most common regimens included rituximab (41%), cladribine (18%), and vemurafenib-based regimens (18%). The CR rate after third-line therapy was 50%. For patients receiving rituximab monotherapy third-line (n = 7), 43% had a CR and 14% had a PR. For patients receiving cladribine monotherapy third-line (n = 3), 33% had a CR. For patients receiving vemurafenib-based regimens third-line (n = 3), 67% had a CR and 33% had a PR.

Overall, treatment-related hospitalizations for first-line therapy occurred in 27% of patients. 50% of patients receiving first-line cladribine with rituximab had treatment-related hospitalizations. 25% of patients receiving first-line vemurafenib-based treatment had treatment-related hospitalizations. 23% of patients receiving first-line cladribine monotherapy had treatment-related hospitalizations. 20% of patients receiving first-line rituximab monotherapy had treatment-related hospitalizations.

Overall, after a median follow-up of 6.6 years (range 0.1–46), estimated OS was 96.6% at 5 years, 85.7% at 10 years, and 80.3% at 15 years. The median OS was 24.5 years [95% CI: 18.3, not reached]. Estimated PFS was 95.1% at 1 year, 89.9% at 3 years, 74.8% at 5 years, and 50.8% at 10 years. Median PFS was 12.2 years [95% CI: 7.0, not reached]. Estimated OS for first-line cladribine monotherapy was 100% at 5 years and 86.5% at 10 years. Estimated OS for first-line vemurafenib-based treatment was 85.7% at 5 years and 85.7% at 10 years.

Conclusions This large real-world cohort provides important insights into the long-term management of HCL. Cladribine-based regimens remain the predominant first-line approach, with high response rates and durable remissions. However, treatment-related toxicity is common. Outcomes in later lines remain favorable, particularly with re-treatment using purine analogs or combination regimens. These findings underscore the importance of individualized treatment planning and the continued need for real-world evidence to inform care in rare hematologic malignancies.