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1506 Venetoclax, Cladribine and Cytarabine for the Treatment of Relapse/Refractory Acute Lymphoblastic Leukemia: Interim Analysis of a Phase 2 Trial

Program: Oral and Poster Abstracts
Session: 614. Acute Lymphoblastic Leukemias: Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster I
Hematology Disease Topics & Pathways:
Combination therapy, Therapies
Saturday, December 9, 2023, 5:30 PM-7:30 PM

Yan-yan Li1*, Hai-xia Zhou2*, Si-man Huang2*, Chao-Ling Wan2*, Ming-zhu Xu2*, Wen-jie Gong2*, Chong-Sheng Qian2*, De-pei Wu3, Haiping Dai2* and Sheng-Li Xue4*

1The First Affiliated Hospital of Soochow University, Suzhou, AL, China
2The First Affiliated Hospital of Soochow University, Suzhou, China
3National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China, Suzhou, China
4Department of Hematology, The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, Suzhou, China

Venetoclax, cladribine and cytarabine for the treatment of relapse/refractory acute lymphoblastic leukemia: interim analysis of a phase 2 trial

Background: Philadelphia chromosome-negative acute B lymphoblastic leukemia (Ph- B-ALL) accounts for approximately 60-70% of adult B-ALL. Patients with relapse/refractory (R/R) Ph- B-ALL was reported to have a poor prognosis. Immunotherapies such as blinatumomab, CAR T-cell therapy achieved high response rate for Ph- B-ALL. However, salvage chemotherapies are also worth of investigation because many patients can’t afford immunotherapies. We found that venetoclax, cladribine and low-dose cytarabine had synergistic cell toxicity against B-ALL cell line RS4;11 in our previously in vitro studies. Based on these findings, we designed a multicenter, phase 2 study utilizing the venetoclax, cladribine and cytarabine (CAV) regimen for the treatment of R/R B-ALL (NCT05657652).

Methods: The CAV regimen consisted of cladribine 5 mg/m2/day from day 1 to day 3 or day 5, cytarabine 20mg/m2, q12h, for 7-10 days and venetoclax 100mg d1, 200 mg d2, 400 mg/day from day 3 to day 28. Bone aspiration evaluation was performed at 14-28 days after the completion of CAV regimen. Treatment responses were evaluated according to the NCCN guidelines. The threshold of MRD negativity was defined as less than 0.01% as detected by multiparameter flow cytometry.

Results: Since February 2021, a total of 16 patients with R/R Ph- B-ALL were enrolled in this study. Baseline characteristics of these patients were summarized in Table 1. The median age was 36 years (range, 13-66 years), and 12/16 (75%) patients were male. Among them, 12 patients (75%) had relapsed Ph- B-ALL and 4 patients (25%) had refractory Ph- B-ALL. One patient had concurrent active central nervous system leukemia. One patient had a complex karyotype, and two patients had TP53 mutations. Treatment responses were shown in Table 2. 12/16 (75%) patients responded to CAV regimen after one cycle of CAV regimen, with 3/16 (18.75%) with complete remission (CR), 8/16 (50%) with CRi, and 1/16 (6.25%) with morphology leukemia-free state (MLFS). Among patients who achieved treatment response, 9/12 (75%) patients attained MRD negativity. During the treatment with the CAV regimen, one patient (1/16, 6.3%) developed grade 4 tumor lysis syndrome. 4/16 (25%) patients suffered grade 3 to 4 infections. Grade 1 to 2 gastrointestinal reactions and liver dysfunction were observed in 8/16 (50%) and 5/16 (31.3%) patients, respectively. The 60-day mortality rate was 6.3%. Two patients who relapsed after CAV treatment re-achieved remission after CART therapy. Nine patients received allo-HSCT after CAV regimen. With a median follow-up of 11 months (range, 0.3-28 months), the estimated 1-year overall survival rate was 76.2% and 1-year event-free survival rate was 38.4%. The survival swimming plot was shown in Figure 1. The median OS was not reached and the median EFS was 13 months. The cumulative relapse rate was 31.3% (5/16). At the last follow-up, two patients died of relapse, one patient died of cerebral hemorrhage and one patient died of sepsis.

Conclusion: In summary, our results demonstrated that CAV regimen showed encouraging efficacy and safety in treating R/R Ph- B-ALL patients.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH