According to the results of a 3-decades-long, large, international study published in Blood Advances, researchers observed high response rates and continuous complete responses (CR) in patients treated with frontline cladribine for symptomatic hairy cell leukemia (HCL).
“Cladribine is universally regarded as the frontline treatment of choice for symptomatic [HCL], as it has transformed an almost incurable disease into a well-controllable condition,” the researchers wrote in their report. “[However,] the published international experience with frontline cladribine mainly consists of single-institution retrospective analyses, sometimes with a limited number of patients.”
The researchers reported on the long-term clinical experience at 4 European centers that treated with cladribine and followed a broad series of patients with treatment-naïve HCL between 1969 and 2018.
For the retrospective study, the team reviewed disease-specific patient records at each center. Among patients requiring treatment for HCL who received frontline cladribine, responses were classified according to the Consensus Resolution criteria published in 1987. The primary outcomes were long-term overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) rates.
The study included 384 patients with HCL. The median patient age at diagnosis was 56 years (range, 25-85). The majority (87%) of patients were male. All patients received cladribine as frontline systemic therapy. Most patients (54%) were treated between 2000 and 2009, followed by 27% between 2010 and 2019, and 18% between 1990 and 1999.
Across the centers, the overall response rate was 94% (range, 86-100). CR was achieved in 72% of cases (range, 54-85), and 76% of patients did not require further treatment after the initial course of cladribine. Among patients achieving CR, 54% experienced no further relapse or progression over time, with a median follow up duration of 8.5 years (range, 1-22). The researchers found that 20% of patients maintained continuous CR (≥5 years), corresponding to 28% of all patients with CR.
The median OS was 25 years, with 48% of patients alive at 28 years. The median PFS was 13 years; the PFS rate was 43% at 22 years. The median DFS was 11 years; the DFS rate was 26.5% at 22 years. The PFS and DFS rates were 77% and 73% at 5 years, 58% and 51% at 10 years, and 43% and 35% at 20 years, respectively.
Cladribine treatment was discontinued early in 18 cases due to hematologic toxicity (n=5) and fever (n=5), sepsis (n=3), pneumonia, gastrointestinal bleeding, military tuberculosis, hepatic toxicity, and cutaneous rash (n=1 each). The team reported 4 deaths due to secondary neoplasms (lung adenocarcinoma, n=2; acute myeloid leukemia, n=1; and colon carcinoma, n=1).
“Besides reporting data on a significant number of patients treated homogeneously at 4 centers of excellence with experience in the management of HCL, this work displays the first international effort in collecting data on symptomatic HCL patients treated with upfront cladribine since its introduction in Europe with a long-term follow up,” the study authors explained. “These results represent the everyday clinical practice with HCL patients at European sites, and outcomes reported for each participating center reflect the efficacy of cladribine as frontline treatment.”
Broccoli A, Argnani L, Cross M, et al. A 3-decade multicenter European experience with cladribine as upfront treatment in 384 patients with hairy cell leukemia. Blood Adv. 2022;6(14):4224-4227. doi:10.1182/bloodadvances.2022007854