维奈克拉治疗恶性血液病异基因造血干细胞移植后复发25例疗效及安全性

OBJEGTIVE: To investigate the efficacy and safety of preemptive/salvage therapy with venetoclax (VEN) in patients with recurrence after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: Retrospective analysis the clinical data of 25 patients with minimal residual disease (MRD) positive or morphological recurrence after allo-HSCT treated with VEN in the hematological Hospital of Chinese Academy of Medical Sciences from 2021.2 to 2021.11, there were 15 MRD positive patients (preemptive treatment group) and 10 morphological recurrence patients (salvage treatment group). The dose of VEN in both groups was 400 mg/d, which was reduced to 100 mg/d when combined with azole antifungal drugs. RESULTS: ①In the preemptive group, there were 7 males and 8 females, with a median age of 32 (18–52) years; There were 13 cases of acute myeloid leukemia (AML), 1 case of acute lymphoblastic leukemia (ALL) and 1 case of primary myelofibrosis (PMF); the median time from MRD positive to the application of VEN was 2.5 (0–12.5) months. The median course of treatment was 2 (1–4). On the 7th day of the first course of treatment, the median concentration of VEN was 1945 (688–5383) µg/L. After one course of VEN treatment, MRD in 8 patients turned negative (major responses), MRD in 4 patients decreased by 50％ compared with that before treatment, 3 cases were ineffective, and the overall response rate (ORR) was 80％ (12/15). On the 7th day of treatment, 3 of the 9 patients with VEN blood concentration <1 000 µg/L or >3 000 µg/L turned negative for MRD (33.3％), and 5 of the 6 patients with VEN blood concentration between 1000 and 3000 µg/L turned negative for MRD (83.3％). Grade 3/4 neutropenia occurred in 5 patients (33％) and grade 3/4 thrombocytopenia occurred in 5 patients (33％), there were no new cases of severe infection and death. ②In the salvage group, there were 7 males and 3 females, with a median age of 44 (28–59) years; there were 6 cases of AML, 2 cases of ALL, 1 case of atypical chronic myeloid leukemia (aCML), 1 case of refractory hemopenia with multiline dysplasia (MDS-RCMD); the median time from relapse to application of VEN was 0 (0–1) months. The median treatment was 1 (1–2) course. The median concentration of VEN on the 7th day of the first course of treatment was 2 419 (1 200–6 155) µg/L. After one course of VEN treatment, 3 cases achieved complete remission (CR) (major responses) and 3 cases achieved partial remission (PR), 4 cases were ineffective and the ORR was 60％ (6/10). On the 7th day of treatment, 1 of the 4 patients with VEN blood concentration >3 000 µg/L achieved CR (25％), and 2 of the 6 patients with VEN blood concentration between 1 000 and 3 000 µg/L achieved CR (33.3％). Grade 3/4 neutropenia and grade 3/4 thrombocytopenia occurred in 10 patients (100％). One patient died of severe pulmonary infection. ③The median follow-up was 4.5 (1–8.5) months. The overall survival rate (OS) of the preemptive group and the salvage group were (70.2±12.7)％ and (50.0±15.8)％, respectively (χ(2)=1.873, P=0.171). The OS of patients with and without primary response to one course of VEN were (90.9±8.7)％ and (36.2±14.7)％ respectively (χ(2)=6.843, P=0.009). Three patients with TP53 mutation achieved the major responses after VEN treatment. CONCLUSION: Preemptive/salvage therapy with VEN after allo-HSCT in patients with hematological malignancies is effective and well tolerated, monitoring the concentration of VEN is expected to improve the curative effect. The prognosis of patients who fail to reach the major responses after one course of preemptive/salvage treatment with VEN is poor, so they need to switch to other treatment schemes as soon as possible.