Patients with primary advanced MDS or t-MDS/AML treated with venetoclax combination therapies
| Study . | Age (y) . | Diagnosis . | Genetics . | Previous lines . | Venetoclax combination therapy . | Response . | HCT . | Outcome (disease status/cause of death) . |
|---|---|---|---|---|---|---|---|---|
| Winters 2021 | 7 | MDS-EB/RAEB in SDS | Mon7, ETV6, GATA2 | 0 | VEN + AZA (1 cycle) | CR (morphological <5%; cytogenetic monosomy 7 10%) | Yes | Alive; disease-free |
| Marinoff et al29 | 17 | MDS | GATA2 germ line | 1 | VEN + AZA | NR | Yes | Dead; relapse after HCT |
| Masetti et al31 | 15 | MDS-EB | LIG4 and SH2B3 germ line, mon7, RIT1, EZH2, SETBP1, ASXL1, ETV6 | 0 | VEN + cytotoxic (IDA-FLA) (1 cycle) | CR | Yes | Alive; disease-free |
| Masetti et al31 | 14 | MDS-EB | Del7q | 4 | VEN + DEC (5 cycles) | CR∗ | Yes | Dead; TRM |
| Winters 2021 | 8 | MDR-AML/RAEB-t in NF1 | Del17p/loss TP53, ASXL1, TET2 | 0 | VEN + AZA (3 cycles) | CR (morphological <5%; cytogenetic persistence del17p/loss TP53) | Yes | Alive; relapse cytogenetic del17/TP53 and MRD pos† |
| Bobeff et al28 | <6 | MDR-AML in NF1 | Mon7 | 1 | VEN + cytotoxic therapy (IDA-FLA) (1 cycle) | CR | Yes | Dead; relapse post-HCT |
| Bobeff et al28 | 6-10 | MDR-AML in familial platelet disorder | RUNX1 | 4 | VEN + cytotoxic therapy (Idarubicin + ARA-C) (1 cycle) | NR | No | Dead; PD before HCT |
| Marinoff et al29 | 14 | MDR-AML in SDS | IDH1, KMT2A | 0 | VEN + DEC | CR (MRD neg) | Yes | Alive; disease-free |
| Raedler et al61 | 16 | MDR-AML/RAEB-t | Complex karyotype | 2 | VEN + DEC (4 cycles) | CR (for 10 months, then molecular relapse) | No | Alive; molecular relapse‡ |
| Naviglio et al62 | 14 | MDR-AML in SDS | neg | 2 | VEN + AZA (1 cycle) | PR | No | Dead; PD before HCT |
| Wen et al41 | 3 | MDR-AML | Complex karyotype, NRAS | 1 | VEN + AZA | CR (MRD neg) | Yes | Alive; disease-free |
| Ma et al63 | 7 | MDS/MDR-AML in FA§ | NPM1, GATA2, WT1 | 1 | VEN+AZA (2 cycles) | CR (MRD neg) | Yes | Alive; disease-free |
| Masetti et al31 | 17 | MDR-AML | FLT3, WT1 | 1 | VEN + AZA (1 cycle) | NR | Yes | Dead; TRM |
| Masetti et al31 | 14 | MDR-AML | WT1 | 2 | VEN + AZA (1 cycle) + VEN + ARA-C (1 cycle) | CR | Yes | Dead; relapse post-HCT |
| Bobeff et al28 | 6-10 | t-AML | KMT2A, t (9;11) | 1 | VEN + ARA-C (1 cycle) | CR (MRD neg) | Yes | Alive; disease-free |
| Marinoff et al29 | 17 | t-AML | Mon7, t (7;11), PTPN11, SED2, RUNX1, BCOR | 3 | VEN + DEC | PR | No | Dead; PD before HCT |
| Winters 2021 | 11 | t-MDS/AML | RUNX1 | 1 | VEN + AZA (9 cycles) | CR (MRD neg) | No | Alive; disease-free‖ |
| Marinoff et al29 | 9 | t-MDS | PTPN11 | 1 | VEN + DEC | PR (stable disease) | No | Dead; PD before HCT |
| Masetti et al31 | 7 | t-MDS/AML | T (11;17), KMT2A | 1 | VEN + IDA-FLA (2 cycles) | CRi | Yes | Alive; disease-free |
| Masetti et al31 | 5 | t-MDS/AML | t (9;11), SDHC, KMT2A | 1 | VEN + IDA-FLA (2 cycles) | CRi | Yes | Alive; disease-free |
| Masetti et al31 | 1 | t-MDS/AML | t (4;11), KMT2A | 1 | VEN + ARA-C + idarubicin | NR | No | Dead; PD before HCT |
| Masetti et al31 | 10 | t-MDS/AML | Mon7 | 1 | VEN + AZA (15 cycles) | PR (stable disease)¶ | Yes | Alive; disease-free |
| Masetti et al31 | 10 | t-MDS/AML | Del3q, PTPN11, WT1 | 1 | VEN + AZA | NR | Yes | Alive; disease-free |
| Masetti et al31 | 6 | t-MDS/AML | t (11;19), KMT2A | 2 | VEN + AZA (5 cycles) | PR | No | Dead; PD before HCT |
| Masetti et al31 | 9 | t-MDS/AML | Mon7, TP53 | 1 | VEN + AZA (1 cycle) | PR | Yes | Alive; disease-free |
| Masetti et al31 | 14 | t-MDS/AML | Mon7, CBL, KRAS, ASXL2 | 1 | VEN + AZA (2 cycles) | CR | Yes | Alive; disease-free |
| Masetti et al31 | 6 | t-MDS/AML | t (9;11), KMT2A | 1 | VEN + FLA (1 cycle); VEN + AZA (1 cycle) | CR (MRD neg) | Yes | Alive; disease-free |
| Study . | Age (y) . | Diagnosis . | Genetics . | Previous lines . | Venetoclax combination therapy . | Response . | HCT . | Outcome (disease status/cause of death) . |
|---|---|---|---|---|---|---|---|---|
| Winters 2021 | 7 | MDS-EB/RAEB in SDS | Mon7, ETV6, GATA2 | 0 | VEN + AZA (1 cycle) | CR (morphological <5%; cytogenetic monosomy 7 10%) | Yes | Alive; disease-free |
| Marinoff et al29 | 17 | MDS | GATA2 germ line | 1 | VEN + AZA | NR | Yes | Dead; relapse after HCT |
| Masetti et al31 | 15 | MDS-EB | LIG4 and SH2B3 germ line, mon7, RIT1, EZH2, SETBP1, ASXL1, ETV6 | 0 | VEN + cytotoxic (IDA-FLA) (1 cycle) | CR | Yes | Alive; disease-free |
| Masetti et al31 | 14 | MDS-EB | Del7q | 4 | VEN + DEC (5 cycles) | CR∗ | Yes | Dead; TRM |
| Winters 2021 | 8 | MDR-AML/RAEB-t in NF1 | Del17p/loss TP53, ASXL1, TET2 | 0 | VEN + AZA (3 cycles) | CR (morphological <5%; cytogenetic persistence del17p/loss TP53) | Yes | Alive; relapse cytogenetic del17/TP53 and MRD pos† |
| Bobeff et al28 | <6 | MDR-AML in NF1 | Mon7 | 1 | VEN + cytotoxic therapy (IDA-FLA) (1 cycle) | CR | Yes | Dead; relapse post-HCT |
| Bobeff et al28 | 6-10 | MDR-AML in familial platelet disorder | RUNX1 | 4 | VEN + cytotoxic therapy (Idarubicin + ARA-C) (1 cycle) | NR | No | Dead; PD before HCT |
| Marinoff et al29 | 14 | MDR-AML in SDS | IDH1, KMT2A | 0 | VEN + DEC | CR (MRD neg) | Yes | Alive; disease-free |
| Raedler et al61 | 16 | MDR-AML/RAEB-t | Complex karyotype | 2 | VEN + DEC (4 cycles) | CR (for 10 months, then molecular relapse) | No | Alive; molecular relapse‡ |
| Naviglio et al62 | 14 | MDR-AML in SDS | neg | 2 | VEN + AZA (1 cycle) | PR | No | Dead; PD before HCT |
| Wen et al41 | 3 | MDR-AML | Complex karyotype, NRAS | 1 | VEN + AZA | CR (MRD neg) | Yes | Alive; disease-free |
| Ma et al63 | 7 | MDS/MDR-AML in FA§ | NPM1, GATA2, WT1 | 1 | VEN+AZA (2 cycles) | CR (MRD neg) | Yes | Alive; disease-free |
| Masetti et al31 | 17 | MDR-AML | FLT3, WT1 | 1 | VEN + AZA (1 cycle) | NR | Yes | Dead; TRM |
| Masetti et al31 | 14 | MDR-AML | WT1 | 2 | VEN + AZA (1 cycle) + VEN + ARA-C (1 cycle) | CR | Yes | Dead; relapse post-HCT |
| Bobeff et al28 | 6-10 | t-AML | KMT2A, t (9;11) | 1 | VEN + ARA-C (1 cycle) | CR (MRD neg) | Yes | Alive; disease-free |
| Marinoff et al29 | 17 | t-AML | Mon7, t (7;11), PTPN11, SED2, RUNX1, BCOR | 3 | VEN + DEC | PR | No | Dead; PD before HCT |
| Winters 2021 | 11 | t-MDS/AML | RUNX1 | 1 | VEN + AZA (9 cycles) | CR (MRD neg) | No | Alive; disease-free‖ |
| Marinoff et al29 | 9 | t-MDS | PTPN11 | 1 | VEN + DEC | PR (stable disease) | No | Dead; PD before HCT |
| Masetti et al31 | 7 | t-MDS/AML | T (11;17), KMT2A | 1 | VEN + IDA-FLA (2 cycles) | CRi | Yes | Alive; disease-free |
| Masetti et al31 | 5 | t-MDS/AML | t (9;11), SDHC, KMT2A | 1 | VEN + IDA-FLA (2 cycles) | CRi | Yes | Alive; disease-free |
| Masetti et al31 | 1 | t-MDS/AML | t (4;11), KMT2A | 1 | VEN + ARA-C + idarubicin | NR | No | Dead; PD before HCT |
| Masetti et al31 | 10 | t-MDS/AML | Mon7 | 1 | VEN + AZA (15 cycles) | PR (stable disease)¶ | Yes | Alive; disease-free |
| Masetti et al31 | 10 | t-MDS/AML | Del3q, PTPN11, WT1 | 1 | VEN + AZA | NR | Yes | Alive; disease-free |
| Masetti et al31 | 6 | t-MDS/AML | t (11;19), KMT2A | 2 | VEN + AZA (5 cycles) | PR | No | Dead; PD before HCT |
| Masetti et al31 | 9 | t-MDS/AML | Mon7, TP53 | 1 | VEN + AZA (1 cycle) | PR | Yes | Alive; disease-free |
| Masetti et al31 | 14 | t-MDS/AML | Mon7, CBL, KRAS, ASXL2 | 1 | VEN + AZA (2 cycles) | CR | Yes | Alive; disease-free |
| Masetti et al31 | 6 | t-MDS/AML | t (9;11), KMT2A | 1 | VEN + FLA (1 cycle); VEN + AZA (1 cycle) | CR (MRD neg) | Yes | Alive; disease-free |
ARA-C, cytarabine; AZA, azacytidine; CRi, complete response with incomplete recovery; DEC, decitabine; FA, Fanconi anemia; FLA, fludarabine, cytarabine; IDA-FLA, fludarabine, cytarabine, idarubicin; IDH1, isocitrate dehydrogenase 1; Mon7, monosomy 7; N/A, not available; NF1, neurofibromatosis type 1; PD, progression of disease; PTPN11, protein tyrosine phosphatase nonreceptor type 11; RAEB, refractory anemia with excess of blasts; RAEB-t, refractory anemia with excess of blasts in transformation; SDS, Shwachman-Diamond syndrome; TP53, tumor protein 53; TRM, transplant-related mortality; VEN, venetoclax.
CR after 2 cycles, maintained for 10 months, then relapsed, another 3 cycles with response, bridged to HCT.
Received AZA post-HCT.
Therapy ongoing.
Previous HCT for FA; donor-cell derived leukemia (DCL) 43 months after HCT.
Maintaining MRD-negative status after 9 cycles.
Stable disease maintained for 15 cycles, then relapse, received AML-type induction therapy, bridged to HCT.