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Long-Term Study Finds Cladribine Safe, Effective Across All Subtypes of Mastocytosis

December 30, 2021

Ten-year follow-up data from a recent retrospective study published in Blood suggest that cladribine (2-CdA) is an effective and safe treatment option for patients with mastocytosis – a condition with no available curative therapy.

Cladribine, a synthetic purine analog, is one treatment option for mastocytosis; however, because of the rarity of the disease, there is little evidence about its long-term safety and efficacy in patients with the condition, particularly for patients with indolent mastocytosis.

In the current study, Stéphane Barete, MD, PhD, of the Paris-Sorbonne University in France, and colleagues analyzed outcomes of 68 patients with mastocytosis treated with at least one course of cladribine. Patients were identified between March 2001 and June 2010. Fifty-one percent of the study's participants were female, and the mean age at the time of cladribine treatment initiation was 54 years.

The patient population represented all subtypes and stages of the disease:

  • 28 had indolent systemic mastocytosis (ISM; 41%)
  • 17 had systemic mastocytosis with an associated clonal hematologic nonmast cell lineage disease (SM-AHNMD; 25%)
  • 14 had aggressive systemic mastocytosis (ASM; 21%)
  • 6 had cutaneous mastocytosis (CM; 9%)
  • 2 had smouldering systemic mastocytosis (SSM; 3%)
  • 1 had mast cell leukemia (MCL; 1%)

Fifty-three percent of patients had indolent mastocytosis (n=36; defined as CM, ISM, and SSM patients), while 47 percent had advanced mastocytosis (n=32; defined as ASM and AHNMD patients).

Cladribine was delivered in a 0.14 mg/kg dose either daily over a two-hour infusion period (51% of patients received this treatment option) or subcutaneously on days 1 through 5 (49%). Patients received a median of 3.68 course of cladribine courses, with a median time between consecutive treatment courses of 52 days.

With respect to the study's primary endpoint, the overall response rate was 72 percent, with encouraging numbers for major and partial responses, but no instances of complete response (TABLE).

These response rates were similar to those observed in previous studies. "However, in contrast with previous studies, [cladribine] appeared more efficient in indolent mastocytosis patients than in ASM and SM-AHNMD patients (p<0.001)," Dr. Barete and investigators noted. There was no statistically significant difference between the route of administration and the resulting clinical response (p=0.11).

Among the 49 patients who experienced an overall response, 48 completed follow-up (median = 5.8 years; range = 21 days to 9 years). Of these patients, 29 experienced a relapse (60%) and four died (8%). The median duration of relapse-free survival (RFS) or duration of response was 3.7 years, with no significant difference according to subtypes. After univariate analysis, only two factors were significantly associated with a shorter RFS: more than four courses of cladribine (HR=2.79 [1.3-6.02]; p=0.009) and a partial response (HR=2.16 [1.05-4.44]; p=0.03).

At the end of follow-up, 21 patients had died in the study population (31%), for an overall survival rate of 48.5 percent (95% CI 30.2-77.9). Median survival time was 8.2 years and, as expected, indolent subtypes were associated with a longer survival time than advanced subtypes. After multivariate analysis, advanced mastocytosis subtype and age >50 years at diagnosis were significantly associated with higher mortality rates (p=0.001 for both). No case of death was ruled directly related to cladribine treatment, the authors noted.

Cladribine had an acceptable safety profile; most grade 3 or 4 adverse events were related to myelosuppression and infectious causes, with 15 patients (22%) experiencing suspected or confirmed infectious complications during cladribine treatment administration. "We might consider secondarily a lower dose or modified scheme of administration of cladribine for indolent mastocytosis patients to improve [the] benefit/risk balance," the investigators added, but they were unable to analyze different dosing schema due to the current study's retrospective design.

For patients with mastocytosis refractory to multiple symptomatic therapies or those with advanced presentations, cladribine is an effective treatment option, the authors concluded, but "further work is warranted to define optimal regimen as well as clinical relevance of maintenance cladribine therapy during mastocytosis." While cladribine seemed to lead to longer duration of response than reported with other treatments commonly used for mastocytosis (interferon-α and PKC412), Dr. Barete added that "this comparison should be taken cautiously, since our population included less advanced cases."


Barete S, Lortholary O, Damaj G, et al. Long-term efficacy and safety of cladribine (2-CdA) in adult patients with mastocytosis. Blood. 2015 May 22. [Epub ahead of print]

TABLE. Response to Treatment with Cladribine

Total patient population, (n=68)

Indolent mastocytosis


Advanced mastocytosis


Overall response




Major response




Partial response




Complete response 0% 0% 0%


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