Cladribine with Sequential or Concurrent Rituximab: What's the Difference?

Patients with HCL increasingly choose cladribine plus rituximab as their first treatment rather than waiting until relapse for this combination. Some hematologists give cladribine plus sequential rituximab to their patients, while others advise concurrent administration.

How do these approaches differ?

Concurrent administration means starting rituximab on the same day as cladribine. In a randomized phase-two study conducted by researchers at the National Institutes of Health (NIH), patients were randomly assigned to one of two approaches: They were given five days of cladribine with eight weekly doses of rituximab beginning day 1 (concurrent), or they were given the cladribine followed by rituximab delayed by six months or less (delayed or sequential). Patients who received concurrent administration achieved MRD negativity at higher rates.

Sequential administration means administering the cladribine with the rituximab postponed for several weeks or months. In a 2024 manuscript, investigators, including Dr. Farhad Ravandi from MD Anderson Cancer Center, published long-term study results. They used sequential cladribine plus rituximab to treat patients with classic or variant HCL. In this study, the rituximab began about 28 days after the initiation of cladribine. 97% of patients achieved complete remission and only 3% of patients relapsed in the roughly 7.8 years of follow up.

In both studies, patients given cladribine plus rituximab (whether concurrent or sequential) had higher remission rates than those given cladribine alone.

For three decades, single-agent purine analogs like cladribine have been the go-to first-line therapy for hairy cell leukemia. While high complete remission rates are typical, minimal residual disease (MRD) can lead to relapse and additional treatments for the patient. Rituximab has been shown to help eliminate MRD, but its long-term efficacy, timing, and side effects are uncertain. There are concerns about immunosuppression and heightened risks of infection during and after treatment.

Resources:

Dr. Robert Kreitman's study in concurrent treatment:
https://pubmed.ncbi.nlm.nih.gov/32109194/

Dr. Farhad Ravandi's study in sequential treatment:
https://pubmed.ncbi.nlm.nih.gov/38749022/