Table 3 Outcomes according to patient, disease, donor CBU and CAR-NK characteristics

From: Safety, efficacy and determinants of response of allogeneic CD19-specific CAR-NK cells in CD19+ B cell tumors: a phase 1/2 trial

Variable

n (%)

Day + 30 OR (%)*

1-year CR (%)*

1-year PFS (95% CI)†

1-year OS (95% CI)†

Patient and disease characteristics

Diagnosis

 

P = 0.013

P = 0.08

P = 0.46

P = 0.03

 Low-grade NHLa

6

6 (100)

5 (83.3)

50.0 (18.8–81.2)

100

 CLL

6

4 (66.7)

3 (50.0)

33.3 (9.7–69.9)

83.3 (43.7–97.0)

 CLL-RT

5

1 (20.0)

1 (20.0)

20.0 (3.6–62.5)

20.0 (3.6–62.5)

 DLBCL

17

7 (41.2)

5 (29.4)

29.4 (13.2–53.2)

64.7 (41.3–82.7)

 Other

3

0 (0.0)

0 (0.0)

33.3 (6.1–79.2)

66.7 (20.8–93.9)

Age

 

P = 0.75

P = 0.31

P = 0.59

P = 0.97

 <65 years

19

10 (52.6)

9 (47.4)

36.8 (19.1–59.0)

68.4 (45.9–84.7)

 ≥65 years

18

8 (44.4)

5 (27.8)

27.8 (12.5−51.0)

66.7 (43.8–83.7)

Sex

 

P = 0.09

P = 0.17

P = 0.97

P = 0.71

 Male

24

9 (37.5)

7 (29.2)

37.5 (21.1–57.3)

66.7 (46.8–82.0)

 Female

13

9 (69.2)

7 (53.8)

23.1 (8.2–50.3)

69.2 (42.3–87.3)

Karnofsky

 

P = 0.02

P = 0.17

P = 0.87

P = 0.06

 ≤90

24

8 (33.3)

7 (29.2)

33.3 (18.0–53.2)

54.2 (35.1–72.2)

 100

13

10 (76.9)

7 (53.8)

30.8 (12.7–57.7)

92.3 (66.6–98.6)

LDH before lymphodepleting chemotherapy

 

P = 1.0

P = 1.0

P = 0.38

P = 0.98

 Normal

13

6 (46.2)

5 (38.5)

46.2 (23.3–70.9)

64.7 (36.1–85.6)

 Elevated

24

12 (50.0)

9 (37.5)

25.0 (12.0–44.8)

69.7 (49.2–84.5)

Number of prior therapies

 

P = 0.41

P = 0.65

P = 0.86

P = 0.44

 1–2

6

4 (66.7)

3 (50.0)

33.0 (9.5–69.8)

83.3 (43.7–97.0)

 ≥3

31

14 (45.2)

11 (35.5)

32.3 (18.6–49.9)

64.5 (46.9–78.9)

Prior stem cell transplant

 

P = 1.00

P = 1.00

P = 0.45

P = 0.36

 No

27

13 (48.1)

10 (37.0)

29.6 (15.8–48.5)

63.0 (44.2–78.5)

 Yes

10

5 (50.0)

4 (40.0)

40.0 (16.8–68.7)

80.0 (49.1–94.3)

Disease status

 

P = 0.54

P = 0.30

P = 0.58

P = 0.30

 Relapsed

11

7 (63.6)

6 (54.5)

45.5 (21.3–72.0)

81.8 (52.4–94.8)

 Refractory to last therapy

16

7 (43.8)

6 (37.5)

25.0 (10.2–49.4)

68.8 (44.4–85.9)

 Primary refractory

10

4 (40.0)

2 (20.0)

30.0 (10.8–60.3)

50.0 (23.7–76.3)

CBU characteristics

HLA allelic matchb

 

P = 0.85

P = 0.95

P = 0.90

P = 0.45

 0/6

5

3 (60.0)

2 (40.0)

40.0 (11.8–76.9)

60.0 (23.1–88.2)

 1/6

9

5 (55.6)

4 (44.4)

33.3 (12.0–64.5)

88.9 (56.4–98.0)

 2/6

2

1 (50.0)

1 (50.0)

50.0 (9.4–90.6)

50.0 (9.4–90.6)

 3/6

2

0 (0.0)

0 (0.0)

50.0 (9.4–90.6)

100.0

 4/6

19

9 (47.4)

7 (36.8)

26.3 (11.8–48.8)

57.9 (36.3–76.8)

KIR ligand mismatch

 

P = 0.51

P = 1.00

P = 0.35

P = 0.67

 No

21

9 (42.9)

8 (38.1)

28.6 (13.8–50.1)

71.4 (49.9–86.2)

 Yes

16

9 (56.3)

6 (37.5)

37.5 (18.5–61.4)

62.5 (38.6–81.5)

KIR haplotype

 

P = 1.0

P = 0.44

P = 0.79

P = 0.73

 A

8

4 (50.0)

4 (50.0)

37.5 (13.7–69.4)

75.0 (40.9–92.8) 65.5

 B

29

14 (48.3)

10 (34.5)

31.0 (17.2–49.2)

(47.4–80.0)

CBU race

 

P = 0.091

P = 0.035

P = 0.40

P = 0.08

 Other

14

4 (28.6)

2 (14.3)

28.6 (11.7–54.7)

50.0 (26.7–73.3)

 Caucasian

23

14 (60.9)

12 (52.2)

34.8 (18.9–55.1)

78.3 (58.1–90.4)

CBU gender

 

P = 0.18

P = 0.31

P = 0.06

P = 0.12

 Female

15

5 (33.3)

4 (26.7)

20.0 (7.1–45.1)

53.3 (30.1–75.2)

 Male

22

13 (59.1)

10 (45.5)

40.9 (23.2–61.3)

77.3 (56.7–89.9)

Time to freezing

 

P = 0.068

P = 0.017

P < 0.001

P = 0.023

 >24 h

18

6 (33.3)

11 (57.9)

5.6 (1.0–25.7)

50.0 (29.0–71.0)

 ≤24h

19

12 (63.2)

3 (16.7)

57.9 (36.3–76.8)

84.2 (62.3–94.5)

Pre-freezing viability

 

P = 0.41

P = 0.22

P = 0.03

P = 0.39

 <97%

7

2 (28.6)

1 (14.3)

0 (-)

57.1 (25.0–84.1)

 ≥97%

30

16 (53.3)

13 (43.3)

40.0 (24.7–57.6)

70 (52.1–83.4)

NRBC content

 

P = 0.019

P = 0.007

P < 0.001

P = 0.06

 ≤8 × 107 cells

28

17 (60.7)

14 (50.0)

42.9 (26.5–61.1)

75.0 (56.6–87.3)

 >8 × 107 cells

9

1 (11.1)

0 (0.0)

0 (-)

44.4 (18.8–73.4)

TNC content

 

P = 0.73

P = 0.27

P = 0.57

P = 0.20

 ≤25% percentile

26

12 (46.2)

8 (30.8)

26.9 (13.7–46.1)

61.5 (42.6–77.5)

 >25% percentile

11

6 (54.5)

6 (54.5)

45.5 (21.3–72.0)

81.8 (52.4–94.8)

Optimal CBU

 

P = 0.008

P = 0.002

P < 0.001

P = 0.003

 no

21

6 (28.6)

3 (14.3)

4.8 (0.9–22.4)

47.6 (28.3–67.6)

 Yes

16

12 (75.0)

11 (68.8)

68.8 (44.4–85.9)

93.8 (71.4–98.9)

CAR-NK characteristics

Transduction efficiency

 

P = 0.71

P = 0.25

P = 0.17

P = 0.11

 ≤25% percentile

9

5 (55.6)

5 (55.6)

44.4 (15.8–73.1)

44.4 (18.8–73.4)

 >25% percentile

28

13 (46.4)

9 (32.1)

28.6 (15.3–47.0)

75.0 (56.6–87.3)

Fraction expansion

 

P = 0.12

P = 0.43

P = 0.48

P = 0.62

 ≤25% percentile

9

2 (22.2)

2 (22.2)

22.2 (6.3–54.8)

61.5 (35.5–82.3)

 >25% percentile

28

16 (57.1)

12 (42.9)

35.7 (20.6–54.2)

70.8 (50.8–85.1)

Number of days in culture

 

P = 0.75

P = 1.0

P = 0.28

P = 0.24

 15

20

9 (45.0)

8 (40.0)

25.0 (11.2–46.9)

60.0 (38.6–78.2)

 22

17

9 (52.9)

6 (35.3)

41.2 (21.7–64.0)

76.5 (52.7–90.5)

Dose level

 

P = 0.43

P = 0.21

P = 0.39

P = 0.10

 1 × 105 cells/kg

3

2 (66.7)

2 (66.7)

66.7 (20.8–93.9)

66.7 (20.8–93.9)

 1 × 106 cells/kg

4

3 (75.0)

3 (75.0)

25.0 (4.5–70.0)

100.0

 1 × 107 cells/kg

15

5 (33.3)

4 (26.7)

20.0 (7.1–45.1)

46.7 (24.8–69.9)

 8 × 108 cells flat dose

15

8 (53.3)

5 (33.3)

40.0 (19.9–64.2)

80.0 (54.9–92.9)

  1. DLBCL, diffuse large B cell lymphoma.
  2. aLow-grade lymphoma includes follicular lymphoma and marginal zone lymphoma.
  3. bNumber of HLA matches between the CBU and the patient at HLA loci A, B and DRβ1.
  4. *P values were derived by two-tailed Fisher’s exact test.
  5. †P values were derived by two-tailed log-rank test.
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