Venetoclax plus hypomethylating agents versus intensive chemotherapy for hematological relapse of myeloid malignancies after allo-HSCT

Abstract

IntroductionSince allogeneic stem cell transplantation (allo-HSCT) is considered one of the curative treatments for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), hematological relapse following allo-HSCT remained a crucial concern for patients’ survival. MethodsWe retrospectively compared patients who received venetoclax plus hypomethylating agents (VEN+HMA, n=23) or intensive chemotherapy (IC, n=42) for hematological relapse of myeloid malignancies after allo-HSCT. HMA selection included decitabine (n=2) and azacitidine (n=21), and combined donor lymphocyte infusion was administered to 21 and 42 patients in VEN+HMA and IC groups, respectively. ResultsMedian age of all patients was 39 (16-64) years old. Overall response rates, including complete response (CR), CR with incomplete recovery of normal neutrophil or platelet counts (CRi) and partial response (PR), were not significantly different between VEN+HMA and IC groups (60.1% versus 64.3%, P=0.785). CR/CRi rate was 52.2% in VEN+HMA and 59.5% in IC group (P=0.567). The rate of relapse after response was 66.7% in VEN+HMA group and 40.7% in IC group (P=0.176). Median overall survival was 209.0 (95%CI 130.9-287.1) days for VEN+HMA group versus 211.0 (95%CI 28.7-393.3) days for IC group (P=0.491). The incidence of lung infection (17.4% versus 50.0%, P=0.010), thrombocytopenia (73.9% versus 95.2%, P=0.035) and acute graft-versus-host disease (aGvHD) (50.0% versus 13.0%, P=0.003) was significantly higher in IC group. DiscussionIn conclusion, VEN+HMA is not inferior to IC regimen in terms of improving response and survival, and is associated with a lower incidence of adverse events and aGvHD. However, further research is required to enhance long-term survival.

Novel Approaches to Treatment of Acute Myeloid Leukemia Relapse Post Allogeneic Stem Cell Transplantation

“…The majority of patients had overt hematologic relapse and advanced disease stage. Altogether, the response rates ranged between 38% and 64%, whereas the median OS ranged between 2 and 10 months [57][58][59][61][62][63]. Despite disparities due to the great heterogeneity of the included patients, the results appeared slightly better than those obtained with HMA monotherapy.…”

“…Among patients relapsed after HSCT, DLIs were combined with Venetoclax and HMA in a limited number of studies. Along with favorable responses, a low incidence of GvHD as well as good tolerance of treatment were observed [61][62][63]. In a retrospective multicenter trial, Venetoclax monotherapy and DLI at escalating doses were given to 22 patients with early relapse of AML after HSCT.…”

“…Besides efficacy, the addition of Venetoclax to HMA was burdened by severe hematological and infectious complications across reported studies, thus generally limiting the median number of administered cycles to two per patient. Grade III-IV neutropenia and thrombocytopenia are reported in 70-90% of patients, leading to frequent treatment interruptions and dose reductions in order to allow hematological recovery [60][61][62][63]. Despite both antimicrobial and antifungal prophylaxis, grade III-IV infections occurred in 50-70% of cases, including invasive fungal infections and fatal complications [59,60,62,63].…”

“…Grade III-IV neutropenia and thrombocytopenia are reported in 70-90% of patients, leading to frequent treatment interruptions and dose reductions in order to allow hematological recovery [60][61][62][63]. Despite both antimicrobial and antifungal prophylaxis, grade III-IV infections occurred in 50-70% of cases, including invasive fungal infections and fatal complications [59,60,62,63]. Indeed, these results pose a problem of tolerability when Venetoclax is employed in more fragile and immunosuppressed patients, such as those relapsed after HSCT.…”