ASH 2025: HCL Takeaways – Long-Term Results of Cladribine Plus Immediate Rituximab

Each year, the global hematology community gathers at the American Society of Hematology (ASH) Annual Meeting to share the latest advances in blood cancers. The 2025 Annual Meeting took place in Florida. We are launching the ASH 2025: HCL Takeaways blog series to present new insights and data from the meeting relevant to people living with HCL.

Our first post features a poster presented at the meeting by Dr. Robert Kreitman of the National Institutes of Health (NIH).

Robert J. Kreitman, M.D. (NIH)

Phase 2 trial of cladribine plus immediate rituximab for first-line treatment of HCL: Long term follow-up

Why this study matters

Cladribine has long been a primary first-line treatment for Hairy Cell Leukemia (HCL), offering high response rates. However, minimal residual disease (MRD) can persist and may eventually cause relapse.

Summary of the study

This study asked an important question: Can starting rituximab at the same time as cladribine lead to deeper, longer-lasting remissions—and do those benefits hold up many years later?

This NIH phase 2 study followed 59 patients with newly diagnosed, untreated classic HCL who received first-line therapy with:

  • Cladribine, given intravenously over 5 days

  • Rituximab, given weekly for 8 weeks, starting on day one of cladribine

Patients were monitored with blood tests and bone marrow exams using sensitive methods to detect MRD. Follow-up was frequent initially and continued long term, with some patients observed for up to 15 years. This extended follow-up enabled assessment of both response and remission durability.

Key takeaways for patients

1. Very high and durable remission rates

  • All patients achieved a complete remission

  • More than 90% achieved MRD-negative remission

  • The vast majority remained MRD-negative for many years, with a median follow-up of over a decade

2. Relapses were rare

  • Only one relapse occurred after achieving MRD-negative remission among all patients, demonstrating the durability of these responses.

3. MRD sometimes appeared—and disappeared

  • A few patients experienced temporary MRD years after treatment, which later resolved without disease progression. This suggests the immune system may continue to help control HCL long after treatment concludes.

4. Safety remained reassuring over time

  • No new long-term safety concerns were identified. Some patients experienced short-term low platelet counts early in treatment, but no serious bleeding occurred, and overall tolerability was favorable.

What this means for people living with HCL

This long-term study provides strong evidence that cladribine combined with immediate rituximab is a highly effective first-line treatment for classic HCL.

For many patients, this approach offers:

  • Deep remissions

  • Very long treatment-free intervals

  • Excellent long-term disease control

Importantly, these results are supported by years of follow-up, which is especially significant for a rare, chronic leukemia such as HCL.

Looking ahead

Researchers continue to study how MRD status affects long-term outcomes, including time to next treatment. These insights will help refine treatment decisions and further personalize care.

This post is the first in our ASH 2025: HCL Takeaways series. We will continue to share patient-centered summaries of new research, as understanding the science helps patients make informed, confident decisions about their care.

Stay tuned for the next post in the series.

Carlos Guerrero