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Letters to the Editor
searched without 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 syn- drome” OR “MDS” AND “venetoclax”. We performed a gray literature search through i) a manual search of bibli- ographies of all identified studies and ii) conference pro- ceedings and abstracts of relevant annual meetings.
The study selection process is illustrated in Figure 1. The primary outcome was a combined rate of CR/CRi. Secondary outcome was ORR defined as CR + CRi + par- tial response (PR) + morphologic leukemia-free state (MLFS). Responses were reported by the individual pub- lications using either the 2017 European Leukemia Network (ELN) AML response criteria4,5 or International Working Group (IWG) criteria for AML.6-9 Three studies
Table 1. Baseline characteristics of all relapsed/refractory acute myeloid leukemia patients treated with venetoclax among the included studies.
Author Year (Ref.)
Konopoleva et al.7 2016
Huemer et al.9 2019
Aldoss et al.11 2019
DiNardo et al.6 2017
Ram et al.10 2019
Goldberg et al.5 2017
Treatment and treatment schedule
Number Secondary patients AML (%)
Number prior HMA treatment (%)
24 (75%)
7 (100%)
46 (51%)
33 (77%)
23 (100%)
16 (76%)
7 (88%)
Venetoclax
800 mg/day (dose ramp up from 20 mg/day to target within 6 days; escalation
to 1,200 mg/day permitted) Venetoclax 800 mg/day (dose ramp up from 20 mg/day to target within 6 days)
Venetoclax + AZA (9 patients) or DEC (81 patients);
no dosing specified
Venetoclax + AZA
(8 patients), DEC (23 patients), LDAC (8 patients), or other (4 patients)
32 17 (54%)
7 7 (100%)
90 22 (24%)
43 13 (31%)
ELN
risk classification
Not reported
Not
reported
Favorable: 8% Intermediate: 26% Adverse: 66%
Favorable: 5%
Intermediate: 49% Adverse: 47%
Favorable: 9% Intermediate: 48% Adverse: 43%
Favorable: 10%
Outcomes
ORR: 19% CR/CRi: 6%/13% Median OS: 4.7 months
ORR: 29%
CR/CRi: 29%/0%
Median OS: 1.8 months (12.1 months in responders vs. 0.8 months in non-responders) ORR: 46% (AZA+VEN: 33%;
DEC + VEN: 47%) CR/CRi: 26%/20% Median OS: 7.8 months (16.6 months in responders vs. 5.1 months in non-responders) ORR: 21% (LDAC+VEN:
13%; AZA+VEN: 38%;
DEC + VEN: 22%) CR/CRi: 5%/7%
Median OS: 3.0 months (4.8 months in responders) ORR: 43%
CR/CRi: 21.5%/21.5% Median OS: 5.6 months (10.8 months in responders vs. 2.8 months in non-responders) ORR: 29%
Adverse effects
All patients with any AE, 26 patients with grade 3/4
Not
reported
Not reported
All patients
with grade 3/4 AE 72% (infectious)
All patients with AE; no further information provided
Not reported
Venetoclax 100-400 mg/day
+ AZA 37.5-75 mg/m2
for 5-7 consecutive days
or DEC 20 mg/m2
for 5 consecutive days Venetoclax 400-800 mg (5-dayramp-upperiodduringcycle1) + AZA or DEC (8 patients)
or LDAC (16 patients)
2017 Venetoclax 50-600 8 5 (63%) mg/day + AZA (5 patients)
or DEC (1 patients)
or LDAC (2 patients)
23 15 (66%)
24 14 (58%)
Intermediate:28% (LDAC+VEN:23%;AZA+VEN:
Shahswar et al.12
Adverse: 62%
Not reported
50%; DEC + VEN: 0%) CR/CRi: 24% Median OS: not reported Not reported ORR: 75% CR/CRi: 12.5%/37.5% Median OS: 6.6 months
AE: adverse events; AML: acute myeloid leukemia AZA: azacitidine; CR: complete remission; CRi: complete remission with incomplete count recovery; DEC: decitabine; ELN: European Leukemia Network; HMA: hypomethylating agent; LDAC: low-dose cytarabine; ORR: overall response rate; OS: overall survival.
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haematologica | 2020; 105(11)