Researchers reported that cladribine remains a sequential drug that results in clinical improvements in patients with advanced systemic mastocytosis (SM), according to a study published in Blood.

The purine analog cladribine has been used as an off-label treatment for patients with advanced SM for nearly 20 years. However, other drugs such as midostaurin and avapritinib have taken precedence over cladribine due to reports indicating that they result in better response and survival rates. Nevertheless, cladribine remains relevant as a second-line treatment if patients demonstrate intolerance or resistance to these medications. 

The authors of the study sought to investigate the response and resistance to cladribine as a first- and second-line drug in 79 patients with advanced SM. First-line treatments included midostaurin, avapritinib, chemotherapy, and allogeneic hematopoietic stem cell transplantation.

Disease-modifying therapies with a low impact (such as interferon-alpha) and therapies solely directed towards any associated hematologic neoplasm (such as hydroxyurea) were not considered first-line treatments.

Read more about systemic mastocytosis treatment 

Participants were given cladribine at a dose of 0.14 mg/kg/day either subcutaneously or intravenously for the first 5 days of a 28-day course. A median of 3 cycles was applied over a median of 3 months. Of all patients, 41% received 3 or more cycles. As for the 19% of participants who underwent dose reduction, the main reason was prolonged myelosuppression.

The overall response rates of patients who were prescribed cladribine as first- and second-line treatment were 41% and 35%, respectively. Upon adjustment for confounding effects of any of the non-cladribine first-line therapies mentioned, the researchers discovered that leukocytosis (≥16×109/L) and eosinophilia (≥1.5×109/L) were independent adverse prognostic markers for overall survival. High mortality among low- and intermediate-risk patients limited the value of any prognostic models for advanced systemic mastocytosis. 

“Overall, cladribine remains a relevant sequential treatment option for patients with [advanced SM],” the authors of the study concluded.


Lübke J, Naumann N, Kreil S, et al. Response and resistance to cladribine in patients with advanced systemic mastocytosis: a registry-based analysis. Blood. 2022;140(Suppl 1):3970-3971. doi:10.1182/blood-2022-163650