Page 173 - 2020_11-Haematologica-web

Letters to the Editor
did not report which response criteria had been used.10-12 Quality assessments for individual studies using a modified Downs and Black checklist are provided in the
Online Supplementary Table S1.13
Random-effects models were used to pool ORR,
CR/CRi and CR rates. All effect sizes underwent logarith- mic transformation prior to pooling using an inverse vari- ance weighting approach. Heterogeneity of studies was determined using Cochran Q and I2 indices and signifi- cant heterogeneity (I2 > 60%) was further explored with sensitivity analyses. Subgroup analyses were planned for venetoclax or venetoclax + HMA/LDAC. All analyses were performed with Comprehensive Meta-Analysis (CMA version 2.2, Biostat).
We identified 813 publications after removal of dupli- cates. Based on the title and the abstract review studies were excluded if they did not report results from AML or myelodysplastic syndromes (MDS) patients (n=459 studies), were reviews (n=84), basic research articles (n=159), or non-clinical studies (n=36). Of the remaining 75 articles, 34 were excluded because they were com- mentaries (n=11), had insufficient reporting of data (n=20) or listed venetoclax among “other treatments” (n=3). Articles reporting results of venetoclax in the frontline setting, in combination with agents other than HMA or LDAC, or publications of interim data were also
excluded. Of the seven studies included, five were retro- spective studies,5,6,8,11,12 one prospective cohort study,10 and one phase I/II clinical trial.7 Patients were treated with venetoclax monotherapy in two studies7,8 and with vene- toclax in combination with either HMA or LDAC in five studies (Table 1).5,6,10-12
There was a total of 224 patients of whom 219 patients had R/R-AML, three MDS patients, and two blastic plas- macytoid dendritic cell neoplasm (BPDCN) patients. The average median age was 68.9 years (range: 59-76). A total of 156 patients (69.6%) had previously received HMA and 48 patients (21.4%) had a prior allogeneic stem cell transplant. The average median duration of follow-up was 7.3 months (range: 1.8-15.8).
Among patients with a reported cytogenetic profile, 13 (7.3%) patients had a favorable, 61 patients (34.5%) had an intermediate and 102 patients (57.6%) had an unfa- vorable cytogenetic risk profile. Five studies (n=211 patients) reported data on molecular testing which showed rates of IDH1/2, FLT3, NPM1, and TP53 muta- tions of up to 38%, 28%, 13%, and 23%, respectively (Online Supplementary Table S2).6-8,10,11
All seven studies reported the ORR (Figure 2A), com- posite CR/CRi rate (Figure 2B) and CR rate (Figure 2C). For all studies combined, the ORR was 31.1% (95% con- fidence interval [CI]: 21.8-42.2). The ORR was 20.7%
AB
CD
Figure 2. Response to venetoclax in relapsed/refractory acute myeloid leukemia (R/R-AML). Forest plots of odds ratios (squares, proportional to study weights used in meta-analysis, 95% confidence intervals) of response for venetoclax alone and in combination hypomethylating agents (HMA) or low-dose cytarabine (LDAC) with the summary measures (center line of diamond) and associated confidence intervals (lateral tips of diamond). Odds ratios for overall response rate (ORR), combined complete response (CR) and complete response with incomplete count recovery (CRi) rate and CR alone are shown in panel A, B and C respec- tively. Odds ratio for the ORR for patients, who received prior HMA therapy, is shown in panel D.
haematologica | 2020; 105(11)
2661