Table 1.
Main efficacy and safety results from prospective and retrospective studies including R/R AML patients treated with venetoclax-based regimens.
| Authors, Year |
Study Design | Study Population | Median Age (Range) |
Treatment Arms/Regimen | Efficacy Results | Relevant Safety Findings |
|---|---|---|---|---|---|---|
| Venetoclax + HMAs or LDAC for R/R AML | ||||||
| DiNardo et al., 2018 [30] |
Retrospective single-center |
43 R/R patients with myeloid neoplasia (including 39 with AML) | 68 years (25–83) |
VEN 100–800 mg daily + DAC (n = 23), AZA (n = 8), LDAC (n = 8), or other (n = 4) | ORR = 21% CR = 5% CRi = 7% MLFS = 9% |
Grade 3–4 neutropenia; grade 3–4 infections (pneumonia, bacteremia, cellulitis, IFI, and urinary tract infections) |
| Aldoss et al., 2018 [31] |
Retrospective single-center |
33 R/R AML patients | 62 years (19–81) |
VEN 400 mg daily + DAC (n = 31) or AZA (n = 2) | ORR = 64% CR = 30% CRi = 21% MLFS = 12% |
Neutropenic infections (sepsis, pneumonia, colitis, and diarrhea) |
| Aldoss et al., 2019 [32] |
Retrospective single-center |
90 R/R AML patients | 59 years (18–81) |
VEN + DAC (n = 81) or AZA (n = 9) | ORR = 46% CR = 26% CRi = 20% |
NA |
| DiNardo et al., 2020 [33] |
Phase II single-center |
168 AML patients (including 55 R/R AML) | 62 years (43–73) |
VEN 400 mg daily + 10-day DAC | All patients: ORR = 74% CR/CRi = 61% Median DOR = NR - R/R AML patients: ORR = 62% CR = 24% CRi = 18%, MLFS 18% Median DOR = 16.8 months |
Grade 3–4 neutropenia-associated infections (6 grade 5); febrile neutropenia |
| Morsia et al., 2020 [34] |
Retrospective single-center |
42 R/R AML patients (post-HSCT excluded) | 64.5 years (18–79) |
VEN 100 mg daily + DAC (n = 35) or AZA (n = 8) | CR = 19% CRi = 14.3% Median OS = 5 months |
Infections (85.7%), IFI (9.5%), and heart failure (19%) |
| Piccini et al., 2021 [35] |
Retrospective single-center |
47 R/R AML patients | 56 years (33–74) |
VEN 400 mg daily + AZA (n = 29), LDAC (n = 13), or DAC (n = 5) | CR + CRi = 55% (16% MRD-negative) Favorable outcome = Median OS = 10.7 months Bridge to HSCT = 54% (13/24) |
Myelosuppression (100%), including grade 4 neutropenia (100%), grade 4 thrombocytopenia (95.7%), and grade >3 anemia (95.7%); febrile neutropenia; and infections (grade 2, n = 10; grade 3, n = 4; grade 4, n = 2) |
| Stahl et al., 2021 [37] |
Retrospective single-center |
86 R/R AML patients | 67 years (29–86) |
VEN 400/600 mg daily + AZA (n = 35), LDAC (n = 27), or DAC (n = 20) | ORR = 31% (49% vs. 15% vs. 25%) a CR = 14% (26% vs. 7% vs. 0%) a CRi = 10% (11% vs. 4% vs. 20%) a MLFS = 7% (11% vs. 4% vs. 5%) a Median DOR = 7.8 months Median OS = 6.1 months |
NA |
| Feld et al., 2021 [38] |
Retrospective single-center |
44 R/R AML/MDS (39 AML, 5 MDS) | 61.5 years | VEN 400 mg daily + AZA or DAC | ORR = 38.5% CR = 12.8% CRi = 25.6% Median DOR = 6.5 months Median OS = 8.1 months. Bridge to HSCT = 20.5% (8/39) |
Grade 3 infections (59.1%), neutropenic fever (46.5%), and persistent neutropenia (71.8%) |
| Labrador et al., 2022 [39] |
Retrospective multicenter |
51 R/R AML patients | 68 years (25–82) |
VEN 400/600 mg daily + AZA (n = 30), DAC (n = 15), or LDAC (n = 6) | ORR = 22.9% CR = 10.4% CRi = 2% Median OS = 104 days Bridge to HSCT = 20.5% (8/39) |
Neutropenic fever (53%) and bleeding (10%) |
| Venetoclax + intensive chemotherapy for R/R AML | ||||||
| DiNardo et al., 2021 [52] |
Phase Ib/II single-center |
68 AML patients (including 39 R/R AML) | 46 (20–73) | VEN 200/400 mg daily + FLAG-Ida | All patients: ORR = 82% CR = 53% CRh = 15% CRi = 7% MLFS = 4% Median DOR = NR 12-month OS = 70% - R/R AML patients: ORR = 72% CR = 44% CRh = 13% CRi = 14% MLFS = 2% Median DOR = 6-NR 12-month OS = 38–68% |
Grade 3–4 AEs occurring in ≥10% of patients: febrile neutropenia (50%), bacteremia (35%), pneumonia (28%), and sepsis (12%) |
| Wolach et al., 2022 [61] |
Retrospective multicenter |
25 AML patients (including 24 R/R AML) | 53.4 years (30.1–72) |
VEN 400 mg daily + FLAG-Ida | ORR = 76% CR = 40% CRi = 32% MLFS = 4% 12-month OS = 50% Bridge to HSCT = 40% (10/25) |
Blood stream infections (48%) and IFI (32%) |
| Shahswar et al., 2022 [62] |
Retrospective single-center |
37 R/R AML patients | 54 years | FLAVIDA (VEN 100 mg daily + FLA-Ida) | ORR = 78% CR = 54% CRi = 5% Median OS = 12 months Bridge to HSCT or DLIs = 81% |
Bacteremia (27%), sepsis (11%), and fungal pneumonia (11%) |
| Röllig et al., 2022 [63] |
Phase I/II multicenter | 12 R/R AML patients | 56 years (40–70) |
VEN 400 mg daily + HAM | CR + CRi = 92% Bridge to HSCT = 45% (5/11) |
57 grade 3 AEs (37% of infectious origin) |
| Venetoclax as bridge-to-transplant and salvage approach for post-HSCT relapse | ||||||
| Zappasodi et al., 2021 [64] |
Retrospective single-center |
10 R/R AML patients (2/10 with prior HSCT) |
53 years (23–67) |
VEN 400 mg daily + AZA | ORR = 60% CR = 40% CRi = 10% MLFS = 10% Median OS = 8.9 months Bridge to HSCT = 70% (6 responders, 1 non-responder) |
Myelosuppression, including prolonged grade 3–4 neutropenia (100%); bacterial infections (30%); and IFI (10%) |
| Shahswar et al., 2020 [66] |
Retrospective single-center |
13 R/R AML patients (6/13 with prior HSCT) |
49 years (18–62) |
FLAVIDA (VEN 100 mg daily + FLA-Ida) |
ORR = 69% CR = 54% Cri = 15% Median OS = NR 6-month OS = 76% Bridge to HSCT = 69% (9/13) Post-salvage DLIs = 15% |
Grade 3–4 neutropenic fever (77%); Gram-negative bacteremia (23%); and grade 3–4 neutropenia, anemia, and thrombocytopenia (100%) |
| Abaza et al., 2023 [67] |
Retrospective single-center |
17 AML patients (including 7 R/R AML) | 48 years (21–68) |
VEN 400 mg daily + FLAG-Ida | R/R AML patients: ORR = 100% CR = 57% CRi= 14% MLFS = 14% Median OS = 6.2 months Bridge to HSCT = 57% (4/7) |
NA |
| Byrne et al., 2020 [68] |
Retrospective single-center |
21 patients relapsing with AML post HSCT (primary diagnosis: AML, n = 16; MDS, n = 3; CMML, n = 1; PMF, n = 1) | 64.5 years (34.5–73.7) |
VEN 400–600 + AZA (n = 12), LDAC (n = 5), or DAC (n = 4) | ORR = 47% CR = 29.4% CRi = 17.6% Median OS = 7.8 months Median OS = NR for responders |
All-grade infectious events (61.9%), bacterial pneumonia (33%), suspected fungal pneumonia (19%), and oral infection (9.5%) |
| Joshi et al., 2021 [69] |
Retrospective single-center |
29 AML patients in relapse post HSCT | 58 years (20–72) |
VEN + DAC (n = 18), AZA (n = 8), LDAC (n = 1), or other (n = 2) | ORR = 38% CR + CRi = 27.5% Median DOR = 7 months Median OS = 79 days (403 and 55 in responders and non-responders, respectively) |
Grade 3–4 neutropenia (69%), grade 3–4 thrombocytopenia (65.5%), infections (55%), bacteremia (34.4%), neutropenic fever (17.2%), and fungal infection (3.4%) |
| Zhao et al., 2022 [72] |
Clinical trial single-center |
26 AML patients in relapse post HSCT | 35.2 years | VEN 400 mg daily + AZA, followed by DLIs | ORR = 61.5% CRi = 26.9% PR = 34.6% Median OS = 284.5 days |
Grade 3–4 neutropenia, anemia and thrombocytopenia (100%), neutropenic fever (100%), nausea and vomiting (42.3%), hyperbilirubinemia (15.4%), elevated liver enzymes (11.5%), and all-grade GVHD (23.1%) |
| Amit et al., 2022 [73] |
Retrospective multicenter |
22 AML patients in relapse post HSCT | 65 years (43–75) |
VEN 400 mg daily monotherapy (n = 8) or + AZA (n = 5), sorafenib (n = 5), gilteritinib (n = 3), HiDAC (n = 2), or LDAC (n = 1), followed by DLIs | ORR = 50% CR = 18% CRi = 5% MLFS = 9% Median DOR = 135 days Median OS = 6.1 months |
Grade 3–4 neutropenia (73%), grade 3–4 anemia (55%), grade 3–4 thrombocytopenia (64%), grade 3–4 infection (14%), diarrhea (32%), grade 3–4 acute GVHD (5%), chronic GVHD (27%), and severe chronic GVHD (5%) |
| Zucenka et al., 2021 [74] |
Retrospective single-center |
20 AML patients in relapse post HSCT | 59 years (20–71) |
VEN 600 mg daily + LDAC and D-actinomycin, followed by VEN + DLIs maintenance | ORR = 75% CR = 50% CRi = 0% MLFS = 5% Median OS = 13.1 months |
Febrile neutropenia (75%), bacteremia (40%), pneumonia (30%), septic shock (5%), mucositis (20%), enteritis (30%), grade 3–4 acute GVHD (10%), and TLS (5%) |
Notes: a The reported percentages refer to VEN + AZA, VEN + LDAC, and VEN + DAC combinations. Abbreviations: AEs, adverse events; CMML, chronic myelomonocytic leukemia; CR, complete response; CRh, CR with partial hematologic recovery; CRi, CR with incomplete blood count recovery; DLI: donor lymphocyte infusion; DOR, duration of response; FLA-IDA, fludarabine + cytarabine + idarubicin; FLAG-Ida, fludarabine + cytarabine + G-CSF + idarubicin; GVHD, graft-versus-host disease; HAM, high-dose cytarabine + mitoxantrone; HiDAC, high-dose cytarabine; HMA, hypomethylating agent; HSCT, hematopoietic stem cell transplantation; IC, intensive chemotherapy; IFI, invasive fungal infection; LDAC, low-dose cytarabine; MDS, myelodysplastic syndrome; MLFS, morphological leukemia-free state; MRD, minimal residual disease; NA, not available; NR, not reached; ORR, overall response rate; OS, overall survival; PR, partial response; R/R AML, relapsed/refractory acute myeloid leukemia; TLS, tumor lysis syndrome; VEN, venetoclax.