Venetoclax combined with cladribine in patients with relapsed/refractory (R/R) T-cell prolymphocytic leukemia (T-PLL).

Abstract

e19087 Background: T-cell prolymphocytic leukemia (T-PLL) is an ultra-rare and aggressive mature T-cell leukemia associated with a poor prognosis. First-line therapy is with CD52 monoclonal antibody alemtuzumab and allogenic stem cell transplant (SCT), but treatment is rarely curative. There is a critical need for more active therapies to improve outcomes. The BCL-2 inhibitor venetoclax (VEN) has demonstrated activity in T-PLL. We studied a combination of cladribine plus VEN in 5 patients (pts) with R/R T-PLL to investigate the safety and efficacy of this combination. Methods: We retrospectively analyzed pts ≥ 18 years with R/R T-PLL treated with a backbone of cladribine 5 mg/m2 intravenous (IV) for 5 days with VEN at a target dose of 600-800 mg orally daily (reduced for concomitant drug interactions) on a 28-day cycle. Two pts concomitantly received alemtuzumab, 1 received ruxolitinib, and 2 pts received both. Baseline demographics, cytogenetics and mutations were collected and summarized using descriptive statistics. Response criteria were defined according to the T-PLL consortium and survival analyzed by Kaplan-Meier method. Results: Five pts with a median age of 64 years (range, 59-66) were treated with cladribine + VEN. Pts had a median of 1 prior therapy (range, 1-3), including 3 (60%) with prior SCT. Overall response rate was 100%, including 2 (40%) complete remission with incomplete count recovery (CRi) (with 1 MRD negative CR), and 3 (60%) partial response (PR). A median of 2 cycles were given (range, 1-4). Baseline characteristics are summarized in Table. All five pts had abnormalities of chromosomes 8, 14, and TCL-1 (positive by FISH); 3 had a STAT5B mutation and 1 each had mutations in JAK1, JAK3, and IL7R. Pts had rapid reductions in all T-PLL-related symptoms and signs (i.e., WBC, splenomegaly, effusions, skin lesions, nodes) within the 2 weeks of starting. The regimen was well-tolerated. Two pts had transient grade 1 creatinine elevations and 4 had grade 4 neutropenia that returned to baseline in a median of 67 days (range, 2-93 days). At the time of data review, 1 patient was alive at 8.3 months. The median overall survival (OS) was 5.8 months. Conclusions: The combination of cladribine and VEN in patients with T-PLL refractory to first-line alemtuzumab was well-tolerated and effective. It was associated with rapid disease control, including splenomegaly, fatigue, pleural infiltrates, and skin infiltration. Staging studies to be presented. This encouraging experience should prompt further study as salvage therapy for T-PLL.[Table: see text]