Venetoclax-based combinations for acute myeloid leukemia: optimizing their use in Latin-America

Figures & data

Table 1. Baseline characteristics of 50 patients with acute myeloid leukemia treated with venetoclax-based combinations in Latin America.

Characteristic		First-line		Relapsed/refractory		All patients
		N = 28	%	N = 22	%	N = 50	%
Sex	Women	14	50	13	59.1	27	54
	Men	14	50	9	40.9	23	46
Age	Median (range)	64	(33–84)	40	(16–71)	57	(16–84)
ECOG	Median (range)	2	(1–3)	1	(0–2)	1	(0–3)
HCT-CI	Median (range)	1	(0–4)	0	(0–3)	0	(0–4)
Diagnosis	De novo	17	60.7	20	90.9	37	74
	MDS/MPN	9	32.1	1	4.5	10	20
	Treatment	2	7.1	1	4.5	3	6
WHO 2016	RGA	3	10.7	1	4.5	4	8
	MRC	12	42.9	4	18.2	16	32
	NOS	13	46.4	17	77.3	30	60
ELN 2017	Favorable	3	10.7	0	0	3	6
	Intermediate	6	21.4	4	18.2	10	20
	Adverse	7	25	6	27.3	13	26
	Not determined	12	42.9	12	54.5	24	48

Abbreviations: ECOG: Eastern Cooperative Group Score; HCT-CI: Hematopoietic Cell Transplantation-Specific Comorbidity Index; WHO: World Health Organization 2016 classification; ELN 2017; European Leukemia-Net 2017 risk stratification; MDS/MPN: AML secondary to myelodysplastic or myeloproliferative neoplasms; RGA: recurrent genetic abnormalities; MRC: myelodysplastic related changes; NOS: not otherwise specified.

Table 2. Patterns of treatment, adverse events, and response with venetoclax-based combinations in 50 patients with acute myeloid leukemia.

Pattern		First line		Relapsed/refractory		All patients
		N = 28	%	N = 22	%	N = 50	%
Combination	Aza	18	64.3	12	54.5	30	60
	Ara-C	10	35.7	10	45.5	20	40
Maximum dose	Median (range)	200	(100–400)	400	(100–600)	200	(100–600)
Ramp-up		24	85.7	12	54.5	36	72
Cycles	Median (range)	3	(1–17)	2	(1–6)	2.5	(1–17)
Ven dose reduction		20	71.4	7	31.8	27	54
Prophylactic azole use		24	85.7	17	77.3	41	82
Neutropenia	Grade ≥3	25	89.3	22	100	47	94
Anemia	Grade ≥3	22	78.6	18	81.8	40	80
Thrombocytopenia	Grade ≥3	20	71.4	18	81.8	38	76
Neutropenic fever		16	57.1	15	68.2	31	62
Response	CR	11	39.3	8	36.4	19	38
	CRi	11	39.3	2	9.1	13	26
	PR	4	14.3	1	4.5	5	10
	NR	2	7.1	11	50	13	26
Subsequent HSCT		3	10.7	11	50	14	28

Abbreviations. Aza: azacytidine; Ara-C: cytarabine; CR: complete response; CRi: complete response with incomplete hematopoietic recovery; PR: partial response; NR: no response; MRD: measurable residual disease HSCT: hematopoietic stem cell transplantation.

Figure 1. Outcomes of patients with newly diagnosed AML treated with venetoclax-based combinations. Panel A: Overall survival. Panel B: Event-free survival.

Figure 2. Outcomes of patients with relapsed/refractory AML treated with venetoclax-based combinations. Panel A: Overall survival. Panel B: Event-free survival.

Figure 3. Overall survival of patients with AML according to maximum venetoclax dose reached. Panel A: newly diagnosed patients. Panel B: relapsed/refractory patients.

Figure 4. Overall survival of patients with AML treated with venetoclax-based combinations. Panel A. Prior treatment lines. Panel B. Hematopoietic cell transplantation comorbidity index in newly diagnosed (ND) and relapsed/refractory (RR) patients.

Table 3. Univariate analysis for event-free survival and overall survival in 50 patients with acute myeloid leukemia who received venetoclax-based treatment.

Variable	EFS			OS
	HR	95% CI	p-value	HR	95% CI	p-value
Age	0.98	0.96–1.005	0.13	0,99	0.97–1.01	0.43
Male	0.75	0.35–1.6	0.45	0.53	0.21–1.34	0.18
Secondary AML	0.43	0.15–1.2	0.12	0.3	0.07–1.3	0.3
ECOG ≥2	0.91	0.43–1.95	0.8	1.15	0.47–2.8	0.76
HCT-CI ≥2	2.21	0.97–5	0.06	2.56	0.97–6.7	0.06
Relapsed/refractory	1.83	0.87–3.86	0.11	1.17	0.4–2.8	0.73
Treatment lines (cont)	1.44	0.72–2.85	0.3	5.58	1.4–21.9	0.014
Out-of pocket	0.63	0.3–1.3	0.23	0.5	0.3–1.8	0.5
Lower Ven dose	0.6	0.28–1.3	0.2	0.47	0.19–1.15	0.09
Ven dose ≤200 mg	0.71	0.34–1.5	0.36	0.63	0.26–1.5	0.31
Azole use	0.99	0.4–2.45	0.98	1.83	0.71–4.8	0.21

EFS: Event-free survival. OS: overall survival. ECOG: Eastern Cooperative Oncology Group. HCT-CI: Hematopoietic Cell Transplantation Comorbidity Index.