World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website https://www.wjon.org

Original Article

Volume 14, Number 1, February 2023, pages 40-50

Real-World Experience of Adults With Acute Myeloid Leukemia on Hypomethylating Agents With or Without Venetoclax at a Comprehensive Cancer Center

Figure 1. The selection process for study enrollment. Records were identified by electronic orders according to treatment date and location criteria. Diagnosis and treatment were verified creating the total cohort, all of which were included in the safety analysis. The efficacy analysis was comprised of patients that received the minimum length of treatment as specified.

Figure 2. (a) PFS, first-line. For newly diagnosed patients: in the HMA alone group, 7/9 (77.8%) had a PFS event during follow-up, with a median PFS time of 218 days (95% CI: 36 - not reached). In the VEN + HMA group, 12/18 (66.7%) had a PFS event, with a median PFS time of 266 days (95% CI: 112 - 425). (b) PFS, relapsed or refractory. For relapsed/refractory patients: in the HMA alone group, 11/12 (91.7%) had a PFS event during follow-up, with a median PFS time of 89.5 days (95% CI: 61 - 246). In the VEN + HMA group, 12/13 (92.3%) had a PFS event, with a median PFS time of 130 days (95% CI: 53 - 140). (c) OS, first-line. In newly diagnosed patients: in the HMA alone group, 7/9 (77.8%) patients died during follow-up, with a median survival of 219 days (95% CI: 39 - not reached). In the VEN + HMA group, 10/18 (55.6%) patients died, with a median survival of 331 days (95% CI: 253 - not reached). (d) OS, relapsed or refractory. In relapsed/refractory patients: in the HMA alone group, 11/12 (91.7%) patients died during follow-up, with a median survival of 145.5 days (95% CI: 92 - 246). In the VEN + HMA group, 9/13 (69.2%) patients died, with a median survival of 253 days (95% CI: 129 - not reached). VEN: venetoclax; HMA: hypomethylating agent; PFS: progression-free survival; OS: overall survival; CI: confidence interval.

**Table 1.** Baseline Characteristics
Variable	HMA (n = 38)	VEN + HMA (n = 39)	P-value
^aOne patient in each group did not have cytogenetic data. AML: acute myeloid leukemia; eGFR: estimated glomerular filtration rate; VEN: venetoclax; HMA: hypomethylating agent.
Age at start of treatment	64.6 ± 13.2	68.4 ± 15.1	0.24
Performance status, n (%)			0.05
0	10 (26.3)	2 (5.1)
1	18 (47.4)	26 (66.7)
2	9 (23.7)	10 (25.6)
3	1 (2.6)	1 (2.6)
eGFR ≤ 60 mL/min, n (%)	9 (23.7)	8 (20.5)	0.79
Comorbid conditions, n (%)
Pulmonary	11 (29.0)	14 (35.9)	0.63
Cardiac	23 (60.5)	30 (76.9)	0.14
Renal	7 (18.4)	7 (18.0)	1.0
Hepatic	0 (0)	1 (2.6)	1.0
AML diagnosis, n (%)			1.0
Primary	23 (60.5)	24 (61.5)
Secondary	15 (39.5)	15 (38.5)
Risk level, n (%)			1.0
Poor	32 (86.5)	32 (82.1)
Intermediate	3 (8.1)	4 (10.3)
Good	2 (5.4)	3 (7.7)
Complex karyotype, n (%)	27 (71.1)	22 (56.4)	0.24
FLT3-ITD^a	0 (0)	2 (5.3)	0.49
FLT3-TKD^a	1 (2.7)	3 (7.9)	0.61
NPM1^a	2 (5.4)	5 (13.2)	0.43
Line of therapy, n (%)			1.0
Newly diagnosed	21 (55.3)	22 (56.4)
Relapsed or refractory	17 (44.7)	17 (43.6)
Past HMA use, n (%)	7 (18.4)	10 (25.6)	0.58
HMA selection			< 0.001
Azacitidine	3 (7.9)	22 (56.4)
Decitabine	35 (92.1)	17 (43.6)
Fungal prophylaxis, n (%)	n/a	36 (92.5)	n/a
Posaconazole	n/a	13 (37.8)	n/a
Voriconazole	n/a	1 (2.7)	n/a
Fluconazole	n/a	12 (32.4)	n/a
Isavuconazole	n/a	7 (18.9)	n/a
Caspofungin	n/a	3 (8.1)	n/a

Table 1. Baseline Characteristics

Variable

HMA (n = 38)

VEN + HMA (n = 39)

P-value

^aOne patient in each group did not have cytogenetic data. AML: acute myeloid leukemia; eGFR: estimated glomerular filtration rate; VEN: venetoclax; HMA: hypomethylating agent.

Age at start of treatment

64.6 ± 13.2

68.4 ± 15.1

0.24

Performance status, n (%)

0.05

10 (26.3)

2 (5.1)

18 (47.4)

26 (66.7)

9 (23.7)

10 (25.6)

1 (2.6)

eGFR ≤ 60 mL/min, n (%)

9 (23.7)

8 (20.5)

0.79

Comorbid conditions, n (%)

Pulmonary

11 (29.0)

14 (35.9)

0.63

Cardiac

23 (60.5)

30 (76.9)

0.14

Renal

7 (18.4)

7 (18.0)

1.0

Hepatic

0 (0)

1 (2.6)

1.0

AML diagnosis, n (%)

1.0

Primary

23 (60.5)

24 (61.5)

Secondary

15 (39.5)

15 (38.5)

Risk level, n (%)

1.0

Poor

32 (86.5)

32 (82.1)

Intermediate

3 (8.1)

4 (10.3)

Good

2 (5.4)

3 (7.7)

Complex karyotype, n (%)

27 (71.1)

22 (56.4)

0.24

FLT3-ITD^a

0 (0)

2 (5.3)

0.49

FLT3-TKD^a

1 (2.7)

3 (7.9)

0.61

NPM1^a

2 (5.4)

5 (13.2)

0.43

Line of therapy, n (%)

1.0

Newly diagnosed

21 (55.3)

22 (56.4)

Relapsed or refractory

17 (44.7)

17 (43.6)

Past HMA use, n (%)

7 (18.4)

10 (25.6)

0.58

HMA selection

< 0.001

Azacitidine

3 (7.9)

22 (56.4)

Decitabine

35 (92.1)

17 (43.6)

Fungal prophylaxis, n (%)

n/a

36 (92.5)

n/a

Posaconazole

n/a

13 (37.8)

n/a

Voriconazole

n/a

1 (2.7)

n/a

Fluconazole

n/a

12 (32.4)

n/a

Isavuconazole

n/a

7 (18.9)

n/a

Caspofungin

n/a

3 (8.1)

n/a

**Table 2.** Response Rates
Response	HMA	VEN + HMA
Seven of 21 HMA patients had no biopsy data, and four of 31 VEN + HMA patients had no biopsy data. VEN: venetoclax; HMA: hypomethylating agent; CR: complete remission; ORR: overall response rate; CRi: CR with incomplete count recovery; MLFS: morphological leukemia-free state; TI: transfusion independence.
Total population	n = 21	n = 31
ORR (CR/CRi), n (%)	6/14 (42.9)	16/27 (59.3)
CR, n (%)	2/14 (14.3)	4/27 (14.8)
CRi, n (%)	4/14 (28.6)	12/27 (44.4)
MLFS, n (%)	4/14 (28.6)	6/27 (22.2)
Clinical benefit rate (CR/CRi/MLFS)	10/14 (71.4)	22/27 (81.5)
TI, n (%)	3/21 (14.3)	14/31 (45.2)
First-line	n = 9	n = 18
ORR (CR/CRi), n (%)	4/5 (80.0)	10/15 (66.7)
CR, n (%)	1/5 (20.0)	4/15 (26.7)
CRi, n (%)	3/5 (60.0)	6/15 (40.0)
MLFS, n (%)	0/5 (0)	3/15 (20.0)
Clinical benefit rate (CR/CRi/MLFS)	4/5 (80.0)	13/15 (86.7)
TI, n (%)	2/9 (22.2)	11/18 (61.1)
Relapsed or refractory	n = 12	n = 13
ORR (CR/CRi), n (%)	2/9 (22.2)	6/12 (50.0)
CR, n (%)	1/9 (11.1)	0/9 (0)
CRi, n (%)	1/9 (11.1)	6/12 (50.0)
MLFS, n (%)	4/9 (44.4)	3/12 (25.0)
Clinical benefit rate	6/9 (66.7)	9/12 (75.0)
TI, n (%)	1/12 (8.3)	3/13 (23.1)

Table 2. Response Rates

Response

HMA

VEN + HMA

Seven of 21 HMA patients had no biopsy data, and four of 31 VEN + HMA patients had no biopsy data. VEN: venetoclax; HMA: hypomethylating agent; CR: complete remission; ORR: overall response rate; CRi: CR with incomplete count recovery; MLFS: morphological leukemia-free state; TI: transfusion independence.

Total population

n = 21

n = 31

ORR (CR/CRi), n (%)

6/14 (42.9)

16/27 (59.3)

CR, n (%)

2/14 (14.3)

4/27 (14.8)

CRi, n (%)

4/14 (28.6)

12/27 (44.4)

MLFS, n (%)

4/14 (28.6)

6/27 (22.2)

Clinical benefit rate (CR/CRi/MLFS)

10/14 (71.4)

22/27 (81.5)

TI, n (%)

3/21 (14.3)

14/31 (45.2)

First-line

n = 9

n = 18

ORR (CR/CRi), n (%)

4/5 (80.0)

10/15 (66.7)

CR, n (%)

1/5 (20.0)

4/15 (26.7)

CRi, n (%)

3/5 (60.0)

6/15 (40.0)

MLFS, n (%)

0/5 (0)

3/15 (20.0)

Clinical benefit rate (CR/CRi/MLFS)

4/5 (80.0)

13/15 (86.7)

TI, n (%)

2/9 (22.2)

11/18 (61.1)

Relapsed or refractory

n = 12

n = 13

ORR (CR/CRi), n (%)

2/9 (22.2)

6/12 (50.0)

CR, n (%)

1/9 (11.1)

0/9 (0)

CRi, n (%)

1/9 (11.1)

6/12 (50.0)

MLFS, n (%)

4/9 (44.4)

3/12 (25.0)

Clinical benefit rate

6/9 (66.7)

9/12 (75.0)

TI, n (%)

1/12 (8.3)

3/13 (23.1)

**Table 3.** Comparisons of Risk Stratification by Treatment in Benefiting Patients (CR/CRi/MLFS)
Risk level	HMA (n = 10)	VEN + HMA (n = 22)
VEN: venetoclax; HMA: hypomethylating agent; CR: complete remission; CRi: CR with incomplete count recovery; MLFS: morphological leukemia-free state.
Good, n (%)	0 (0)	3 (13.6)
Intermediate, n (%)	2 (20.0)	1 (4.5)
Poor, n (%)	8 (80.0)	18 (81.8)
Complex karyotype, n (%)	7 (70.0)	13 (59.1)

Table 3. Comparisons of Risk Stratification by Treatment in Benefiting Patients (CR/CRi/MLFS)

Risk level

HMA (n = 10)

VEN + HMA (n = 22)

VEN: venetoclax; HMA: hypomethylating agent; CR: complete remission; CRi: CR with incomplete count recovery; MLFS: morphological leukemia-free state.

Good, n (%)

0 (0)

3 (13.6)

Intermediate, n (%)

2 (20.0)

1 (4.5)

Poor, n (%)

8 (80.0)

18 (81.8)

Complex karyotype, n (%)

7 (70.0)

13 (59.1)

**Table 4.** Toxicity
Toxicity	HMA (n = 38)	VEN + HMA (n = 39)	P-value
ANC: absolute neutrophil count; VEN: venetoclax; HMA: hypomethylating agent; TLS: tumor lysis syndrome.
Dose delay	13 (34.2)	27 (69.2)	0.003
Dose reductions
HMA	4 (10.5)	8 (20.5)	0.35
VEN	n/a	15 (38.5)	n/a
Grade 3/4 neutropenia (ANC < 1,000/µL)	29 (76.3)	39 (100)	0.001
Profound neutropenia (ANC < 100/µL)	20 (52.6)	29 (74.4)	0.06
Recovered	10/20 (50.0)	20/29 (69.0)	0.24
Duration (days), median (Q₁ - Q₃)	13.0 (3.0 - 32.0)	7.5 (5.5 - 18.0)	0.64
Grade 3/4 thrombocytopenia (platelets < 100,000/µL)	35 (92.1)	37 (94.9)	0.67
Grade 3/4 serum creatinine increase	3 (7.9)	4 (10.3)	1.0
Laboratory TLS	0/6 (0)	3 (7.7)	1.0

Table 4. Toxicity

Toxicity

HMA (n = 38)

VEN + HMA (n = 39)

P-value

ANC: absolute neutrophil count; VEN: venetoclax; HMA: hypomethylating agent; TLS: tumor lysis syndrome.

Dose delay

13 (34.2)

27 (69.2)

0.003

Dose reductions

HMA

4 (10.5)

8 (20.5)

0.35

VEN

n/a

15 (38.5)

n/a

Grade 3/4 neutropenia (ANC < 1,000/µL)

29 (76.3)

39 (100)

0.001

Profound neutropenia (ANC < 100/µL)

20 (52.6)

29 (74.4)

0.06

Recovered

10/20 (50.0)

20/29 (69.0)

0.24

Duration (days), median (Q₁ - Q₃)

13.0 (3.0 - 32.0)

7.5 (5.5 - 18.0)

0.64

Grade 3/4 thrombocytopenia (platelets < 100,000/µL)

35 (92.1)

37 (94.9)

0.67

Grade 3/4 serum creatinine increase

3 (7.9)

4 (10.3)

1.0

Laboratory TLS

0/6 (0)

3 (7.7)

1.0