Consolidation outcomes in CPX-351 versus cytarabine/daunorubicin-treated older patients with high-risk/secondary acute myeloid leukemia

Figures & data

Table 1. Baseline demographic and clinical patient characteristics.

	All consolidation		Inpatient^a		Outpatient
	CPX-351 (n = 49)	5 + 2 (n = 32)	CPX-351 (n = 24)	5 + 2 (n = 30)	CPX-351 (n = 25)	5 + 2 (n = 2)
Age
Median (min-max), years	68 (61–75)	68.5 (61–75)	67.5 (61–75)	68.5 (61–75)	69 (61–75)	66 (63–69)
60–69 years, n (%)	30 (61)	20 (63)	17 (71)	18 (60)	13 (52)	2 (100)
70–75 years, n (%)	19 (39)	12 (38)	7 (29)	12 (40)	12 (48)	0
Male sex, n (%)	30 (61)	18 (56)	16 (67)	16 (53)	14 (56)	2 (100)
Race, n (%)
Asian	3 (6)	1 (3)	2 (8)	1 (3)	1 (4)	0
Black or African American	0	2 (6)	0	2 (7)	0	0
White	43 (88)	29 (91)	20 (83)	27 (90)	23 (92)	2 (100)
Other	3 (6)	0	2 (8)	0	1 (4)	0
ECOG PS, n (%)^b
0	15 (31)	14 (44)	6 (25)	13 (43)	9 (36)	1 (50)
1	30 (61)	16 (50)	15 (63)	15 (50)	15 (60)	1 (50)
2	4 (8)	2 (6)	3 (13)	2 (7)	1 (4)	0
AML subtype, n (%)
Therapy-related AML	10 (20)	7 (22)	5 (21)	6 (20)	5 (20)	1 (50)
Antecedent MDS
With prior HMA treatment	9 (18)	9 (28)	7 (29)	9 (30)	2 (8)	0
Without prior HMA treatment	8 (16)	7 (22)	4 (17)	7 (23)	4 (16)	0
Antecedent CMML	4 (8)	3 (9)	3 (13)	3 (10)	1 (4)	0
De novo AML with MDS karyotype	18 (37)	6 (19)	5 (21)	5 (17)	13 (52)	1 (50)
Bone marrow blast percentage, n (%)^c
40%	28 (57)	21 (70)
>40–60%	14 (29)	6 (20)
>60%	7 (14)	3 (10)
Cytogenetic risk by NCCN, n (%)^d
Favorable/intermediate	23 (49)	18 (64)
Unfavorable	24 (51)	10 (36)
FLT3 mutation, n (%)	9 (20)	3 (11)
White blood cell count, n (%)^b
<20 × 10^9/L	46 (94)	29 (91)
≥20 × 10^9/L	3 (6)	3 (9)
Platelet count, n (%)^b
≤50 × 10^9/L	28 (57)	16 (50)
>50 × 10^9/L	21 (43)	16 (50)

Min: minimum; max: maximum; ECOG PS: Eastern Cooperative Oncology Group performance status; AML: acute myeloid leukemia; MDS: myelodysplastic syndrome; HMA: hypomethylating agent; CMML: chronic myelomonocytic leukemia; NCCN: National Comprehensive Cancer Network.

^aIf a patient spent ≥1 day in the hospital during the treatment cycle, that patient was classified as an ‘inpatient’ regardless of the actual setting of treatment administration.

^bAt baseline.

^cData are missing for 2 patients in the 5 + 2 arm.

^dData are missing for 2 patients in the CPX-351 arm and 4 patients in the 5 + 2 arm.

Figure 1. OS in patients who received consolidation. Median OS was prolonged in patients who received CPX-351 throughout induction and consolidation (black line) versus those who received 7 + 3/5 + 2 (grey line). This trend was observed in patients who received consolidation with or without HCT (table).

Table 2. Summary of TEAEs in patients during consolidation treatment.

Frequency of TEAEs, n (%)	During Consolidation 1		During Consolidation 2
	CPX-351 (n = 49)	5 + 2 (n = 32)	CPX-351 (n = 23)	5 + 2 (n = 12)
Any TEAE^a	42 (86)	29 (91)	20 (87)	12 (100)
Febrile neutropenia	10 (20)	6 (19)	6 (26)	3 (25)
Nausea	8 (16)	3 (9)	3 (13)	5 (42)
Constipation	7 (14)	7 (22)	5 (22)	3 (25)
Fatigue	6 (12)	9 (28)	6 (26)	2 (17)
Pyrexia	6 (12)	2 (6)	2 (9)	2 (17)
Epistaxis	6 (12)	1 (3)	2 (9)	1 (8)
Diarrhea	4 (8)	9 (28)	2 (9)	1 (8)
Peripheral edema	4 (8)	7 (22)	4 (17)	1 (8)
Decreased appetite	4 (8)	3 (9)	4 (17)	1 (8)
Chills	3 (6)	3 (9)	7 (30)	1 (8)
Rash	3 (6)	1 (3)	1 (4)	2 (17)
Arthralgia	3 (6)	0	3 (13)	0
Dizziness	2 (4)	6 (19)	5 (22)	0
Headache	2 (4)	3 (9)	2 (9)	2 (17)
Oropharyngeal pain	1 (2)	2 (6)	2 (9)	3 (25)
Skin lesion	0	4 (13)	1 (4)	0
Atrial fibrillation	0	3 (9)	0	2 (17)
Rhinorrhea	0	1 (3)	0	2 (17)
Mucosal inflammation	0	0	3 (13)	1 (8)
Grade 3–5 TEAE^a	19 (39)	12 (38)	13 (57)	6 (50)
Febrile neutropenia	10 (20)	6 (19)	6 (26)	3 (25)
Serious TEAE^a	15 (31)	11 (34)	10 (43)	5 (42)
Febrile neutropenia	6 (12)	4 (13)	2 (9)	3 (25)

TEAE: treatment-emergent adverse event.

^aTable includes all TEAEs reported in ≥10% of patients in either treatment group during Consolidation 1 or 2.

Table 3. Median time to neutrophil and platelet recovery in patients who achieved remission with 1 and 2 consolidation cycles.

	1 consolidation cycle		2 consolidation cycles^a
	CPX-351	5 + 2	CPX-351	5 + 2
CR, n	19	18	21	12
Median (Q1–Q3) time to ANC recovery ≥1000 neutrophils/µL, days	41 (35–48)	32.5 (29–43)	35 (28–41)	33.5 (27–39)
Median (Q1–Q3) time to platelet recovery ≥100,000 platelets/µL, days	43 (34–48)	30 (29–45)	37 (33–49)	35.5 (31–41)
CR + CRi, n	25	20	23	12
Median (Q1–Q3) time to ANC recovery ≥500 neutrophils/µL, days	35 (34–44)	32.5 (29–43)	36 (28–48)	33.5 (27–39)
Median (Q1–Q3) time to platelet recovery ≥50,000 platelets/µL, days	40 (35–43)	30 (28–41)	36 (28–47)	31.5 (27–37)

CR: complete remission; Q: quartile; ANC: absolute neutrophil count; CRi: CR with incomplete platelet or neutrophil recovery. One patient received consolidation but had no CR or CRi and was not included in this analysis.

^aMeasured from the treatment start date.

Table 4. Hospitalization during consolidation.

	CPX-351	5 + 2
Consolidation 1, n	49	32
Outpatient administration, n (%)	25 (51)	2 (6)
Inpatient administration, n (%)^a	24 (49)	30 (94)
Median (min–max) days of treatment cycle spent as inpatient	4.0 (0–28)	7.0 (0–31)
Median (min–max) days of treatment cycle spent as inpatient PPY	33.2 (0–310)	71.0 (0–315)
Median (min–max) days of treatment cycle spent in the ICU	0 (0–0)	0 (0–11)
Median (min–max) days of treatment cycle spent in the ICU PPY	0 (0–0)	0 (0–112)
Consolidation 2, n	23	12
Outpatient administration, n (%)	14 (61)	0 (0)
Inpatient administration, n (%)^a	9 (39)	12 (100)
Median (min–max) days of treatment cycle spent as inpatient	4.0 (0–31)	7.0 (5–28)
Median (min–max) of treatment cycle spent as inpatient PPY	44.3 (0–343)	73.1 (52–292)
Median (min–max) days of treatment cycle spent in the ICU	0 (0–10)	0 (0–17)
Median (min–max) days of treatment cycle spent in the ICU PPY	0 (0–111)	0 (0–177)

Min: minimum; max, maximum; PPY: per patient-year; ICU: intensive care unit.

^aIf a patient spent ≥1 day in the hospital during the treatment cycle, that patient was classified as an ‘inpatient’ regardless of the actual setting at the start of consolidation treatment administration.

Table 5. OS by setting of consolidation administration.

	Inpatient^a		Outpatient
	CPX-351	5 + 2	CPX-351	5 + 2
Consolidation 1, n/N (%)^b	24/49 (49)	30/32 (94)	25/49 (51)	2/32 (6)
Median OS, mo	14.72	9.26	25.43	6.87
HR (95% CI)	0.55 (0.25–1.21)		0.10 (0.01–1.11)
Consolidation 2, n/N (%)	9/23 (39)	12/12 (100)	14/23 (61)	0/12 (0)
Median OS, mo	NR	14.31	26.32	–
HR (95% CI)	0.45 (0.09–2.36)		–

OS: overall survival; HR: hazard ratio; CI: confidence interval; NR: not reached.

^aIf a patient spent ≥1 day in the hospital during the treatment cycle, that patient was classified as an ‘inpatient’ regardless of the actual setting of treatment administration.

^bHere, n denotes the number of patients receiving a specific consolidation cycle in a given setting (inpatient vs. outpatient), and N denotes the number of patients in that treatment arm who received that consolidation cycle.

Data availability statement

All relevant data are provided within the manuscript and supporting files. The study protocol and statistical analysis plan are available as online supplemental content for Lancet JE, et al. JCO. 2018;36(26):2684-2692.