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Letters to the Editor
Venetoclax as monotherapy and in combination with hypomethylating agents or low dose cytarabine in relapsed and treatment refractory acute myeloid leukemia: a systematic review and meta-analysis
Recent clinical data have shown a synergistic effect of venetoclax in combination with the hypomethylating agents (HMA) azacitidine and decitabine (complete remission [CR]/CR with incomplete cell count recovery [CRi]: 73%, median overall survival [OS] of 17.5 months) as well as low-dose cytarabine (LDAC; CR/CRi: 54%; median OS of 10.1 months) in the frontline setting in older patients with acute myeloid leukemia (AML) and those ineligible for intensive chemotherapy leading to approval of both combinations in the US.1,2 However, data on relapsed/refractory (R/R)-AML are scarce and
heterogenous. Outcomes of patients with R/R-AML are dismal with a median OS of 3-7 months and there is no approved standard of care.3 Multiple clinical trials com- bining either venetoclax alone, venetoclax + HMA or venetoclax + LDAC as the backbone of therapy with other novel agents in R/R-AML are ongoing. As many of these trials are not randomized, it is vital to understand the response rate to venetoclax alone and venetoclax + HMA/LDAC in R/R-AML to use it as a benchmark for comparison.
Therefore, we performed a systematic literature review and meta-analysis to objectively assess overall response rates (ORR), and rates of CR/CRi for R/R-AML patients treated with venetoclax or venetoclax + HMA/LDAC.
MEDLINE via PubMed, Ovid EMBASE, the COCHRANE registry of clinical trials (CENTRAL), Scopus and the Web of Science electronic databases were
Figure 1. Flow chart showing study selection as per the MOOSE guidelines. Figure 1 illustrates the search strategy and stepwise process of the study selection used in this meta-analysis. MEDLINE via Ovid, Ovid EMBASE, Scopus, the COHRANE registry of clinical trials (CENTRAL), and the Web of Science electronic data- bases were searched with no language restriction from inception through August 2019, using the following combination of free-text terms linked by Boolean operators: “acute myeloid leukemia” OR “AML” OR “myelodysplastic syndrome” OR “MDS” AND “venetoclax”. Two authors (MS and JPB) independently screened the titles and abstracts of all retrieved studies for eligibility and removed any duplicate records. In a second step, full texts of the potentially eligible studies were reviewed for the final eligibility. Reviews, basic science articles and articles with an insufficient patient number (<5 patients) were excluded. Furthermore, we excluded studies that i) lacked information on either overall response rate (ORR) or complete resposnse (CR) rate, ii) review articles, editorials, and correspon- dence letters that did not report independent data, iii) case series and studies reporting outcomes on fewer than five patients, iiii) studies that did were not conducted in acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) patients.
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