Pharmacodynamics: Peak Level of Cytokines in Serum (Phase 1 and Phase 2 Cohorts 1, 2, and 3)
Study Evaluating the Safety and Efficacy of KTE-C19 in Adult Participants With Refractory Aggressive Non-Hodgkin Lymphoma · Source last updated 2024-06-04
Results reported by the registry submitting party. Population, time horizon, units and missing values must be read together.
Measure
MEDIAN
Unit
pg/mL
Interval / dispersion
Full Range
Time frame
Baseline up to Month 3
What was measured
Peak was defined as the maximum post-baseline level of the cytokine. Following key cytokines were measured: interferon-gamma induced protein 10 (IP-10), ferritin, granzyme B, intercellular adhesion molecule (ICAM-1), interferon-gamma (IFN-gamma), interleukin-1 receptor antagonist (IL-1RA), IL-2, interleukin-2 receptor alpha (IL-2 R alpha), IL-6, IL-7, IL-8, IL-10, IL-15, perforin, tumor necrosis factor alpha (TNF alpha), and vascular cell adhesion molecule- 1 (VCAM-1).
Analysis population: Participants in the Safety Analysis Set were analyzed.
Groups in this outcome
Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemotherapy
Participants with diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), or transformed follicular lymphoma (TFL) received conditioning chemotherapy (fludarabine 30 mg/m\^2 intravenously \[IV\] over 30 minutes and cyclophosphamide 500 mg/m\^2 IV over 60 minutes) on Days -5, -4, and -3; followed by a single infusion of axicabtagene ciloleucel chimeric antigen receptor (CAR) transduced autologous T cells administered IV at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg of body weight (BW) on Day 0.
Phase 2 (Pivotal Study): Cohort 1
Participants with refractory DLBCL received conditioning chemotherapy (fludarabine 30 mg/m\^2 IV over 30 minutes and cyclophosphamide 500 mg/m\^2 IV over 60 minutes) on Days -5, -4, and -3; followed by a single infusion of axicabtagene ciloleucel CAR transduced autologous T cells administered IV at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg of BW on Day 0.
Phase 2 (Pivotal Study): Cohort 2
Participants with refractory PMBCL or TFL received conditioning chemotherapy (fludarabine 30 mg/m\^2 IV over 30 minutes and cyclophosphamide 500 mg/m\^2 IV over 60 minutes) on Days -5, -4, and -3; followed by a single infusion of axicabtagene ciloleucel CAR transduced autologous T cells administered IV at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg of BW on Day 0..
Phase 2 (Safety Management Study): Cohort 3
Participants with relapsed or refractory transplant ineligible DLBCL, PMBCL, or TFL received conditioning chemotherapy (fludarabine 30 mg/m\^2 IV over 30 minutes and cyclophosphamide 500 mg/m\^2 IV over 60 minutes) on Days -5, -4, and -3; followed by a single infusion of axicabtagene ciloleucel CAR transduced autologous T cells administered IV at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg of BW on Day 0. Participants also received a prophylactic regimen of levetiracetam (750 mg orally or IV twice daily (BID) starting on Day 0) and tocilizumab (8 mg/kg IV over 1 hour (not to exceed 800 mg)) on Day 2).
Group identifiers and denominators belong to this outcome only. They may differ in another outcome or in safety reporting.
Analysis denominator · Participants
Group
Source count
Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemotherapy
7
Phase 2 (Pivotal Study): Cohort 1
77
Phase 2 (Pivotal Study): Cohort 2
24
Phase 2 (Safety Management Study): Cohort 3
38
Reported measurements
IP-10
Values in pg/mL · Interval/dispersion: Full Range
Group
Value
Spread
Lower
Upper
Comment
Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemotherapy
2000.0
Not reported
147.0
2000.0
Not reported
Phase 2 (Pivotal Study): Cohort 1
2000.0
Not reported
628.1
2000.0
Not reported
Phase 2 (Pivotal Study): Cohort 2
2000.0
Not reported
434.2
2000.0
Not reported
Phase 2 (Safety Management Study): Cohort 3
2000.0
Not reported
541.0
2000.0
Not reported
Granzyme B
Values in pg/mL · Interval/dispersion: Full Range
Group
Value
Spread
Lower
Upper
Comment
Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemotherapy
33.1
Not reported
0.6
463.8
Not reported
Phase 2 (Pivotal Study): Cohort 1
31.1
Not reported
1.0
3306.0
Not reported
Phase 2 (Pivotal Study): Cohort 2
17.3
Not reported
1.0
406.8
Not reported
Phase 2 (Safety Management Study): Cohort 3
44.1
Not reported
1.0
534.6
Not reported
ICAM-1
Values in pg/mL · Interval/dispersion: Full Range
Group
Value
Spread
Lower
Upper
Comment
Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemotherapy
792754.3
Not reported
537796.8
2424877.7
Not reported
Phase 2 (Pivotal Study): Cohort 1
1322829.3
Not reported
557025.0
7495123.2
Not reported
Phase 2 (Pivotal Study): Cohort 2
989188.4
Not reported
544589.3
4588974.8
Not reported
Phase 2 (Safety Management Study): Cohort 3
1009966.4
Not reported
256768.6
4879749.7
Not reported
IFN-gamma
Values in pg/mL · Interval/dispersion: Full Range
Group
Value
Spread
Lower
Upper
Comment
Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemotherapy
792.0
Not reported
81.1
1876.0
Not reported
Phase 2 (Pivotal Study): Cohort 1
493.8
Not reported
32.4
1876.0
Not reported
Phase 2 (Pivotal Study): Cohort 2
364.9
Not reported
7.5
1876.0
Not reported
Phase 2 (Safety Management Study): Cohort 3
1857.2
Not reported
65.0
1876.0
Not reported
IL-1 RA
Values in pg/mL · Interval/dispersion: Full Range
Group
Value
Spread
Lower
Upper
Comment
Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemotherapy
2173.3
Not reported
544.3
4000.0
Not reported
Phase 2 (Pivotal Study): Cohort 1
2371.2
Not reported
510.8
4000.0
Not reported
Phase 2 (Pivotal Study): Cohort 2
1999.9
Not reported
649.9
4000.0
Not reported
Phase 2 (Safety Management Study): Cohort 3
2160.5
Not reported
653.7
4000.0
Not reported
IL-2
Values in pg/mL · Interval/dispersion: Full Range
Group
Value
Spread
Lower
Upper
Comment
Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemotherapy
18.4
Not reported
3.1
91.0
Not reported
Phase 2 (Pivotal Study): Cohort 1
25.0
Not reported
0.9
123.1
Not reported
Phase 2 (Pivotal Study): Cohort 2
13.4
Not reported
0.9
63.7
Not reported
Phase 2 (Safety Management Study): Cohort 3
20.0
Not reported
0.9
189.4
Not reported
IL-2 R alpha
Values in pg/mL · Interval/dispersion: Full Range
Group
Value
Spread
Lower
Upper
Comment
Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemotherapy
16872.7
Not reported
2189.0
34044.5
Not reported
Phase 2 (Pivotal Study): Cohort 1
14383.7
Not reported
78.0
100000.0
Not reported
Phase 2 (Pivotal Study): Cohort 2
7817.3
Not reported
78.0
66024.6
Not reported
Phase 2 (Safety Management Study): Cohort 3
12386.4
Not reported
3002.6
100000.0
Not reported
IL-6
Values in pg/mL · Interval/dispersion: Full Range
Group
Value
Spread
Lower
Upper
Comment
Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemotherapy
305.3
Not reported
2.4
976.0
Not reported
Phase 2 (Pivotal Study): Cohort 1
89.4
Not reported
3.5
976.0
Not reported
Phase 2 (Pivotal Study): Cohort 2
44.6
Not reported
3.6
976.0
Not reported
Phase 2 (Safety Management Study): Cohort 3
921.8
Not reported
13.3
976.0
Not reported
IL-7
Values in pg/mL · Interval/dispersion: Full Range
Group
Value
Spread
Lower
Upper
Comment
Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemotherapy
51.5
Not reported
31.2
71.5
Not reported
Phase 2 (Pivotal Study): Cohort 1
38.9
Not reported
13.8
153.5
Not reported
Phase 2 (Pivotal Study): Cohort 2
44.1
Not reported
27.9
98.8
Not reported
Phase 2 (Safety Management Study): Cohort 3
38.8
Not reported
19.1
83.8
Not reported
IL-8
Values in pg/mL · Interval/dispersion: Full Range
Group
Value
Spread
Lower
Upper
Comment
Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemotherapy
86.4
Not reported
17.1
750.0
Not reported
Phase 2 (Pivotal Study): Cohort 1
118.4
Not reported
14.2
750.0
Not reported
Phase 2 (Pivotal Study): Cohort 2
77.2
Not reported
9.8
750.0
Not reported
Phase 2 (Safety Management Study): Cohort 3
120.9
Not reported
10.3
750.0
Not reported
IL-10
Values in pg/mL · Interval/dispersion: Full Range
Group
Value
Spread
Lower
Upper
Comment
Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemotherapy
52.5
Not reported
3.8
614.0
Not reported
Phase 2 (Pivotal Study): Cohort 1
43.9
Not reported
0.7
466.0
Not reported
Phase 2 (Pivotal Study): Cohort 2
18.8
Not reported
0.7
263.6
Not reported
Phase 2 (Safety Management Study): Cohort 3
48.2
Not reported
1.8
466.0
Not reported
IL-15
Values in pg/mL · Interval/dispersion: Full Range
Group
Value
Spread
Lower
Upper
Comment
Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemotherapy
57.1
Not reported
18.7
271.3
Not reported
Phase 2 (Pivotal Study): Cohort 1
56.5
Not reported
13.1
226.6
Not reported
Phase 2 (Pivotal Study): Cohort 2
47.6
Not reported
11.3
195.2
Not reported
Phase 2 (Safety Management Study): Cohort 3
50.3
Not reported
21.9
537.3
Not reported
Perforin
Values in pg/mL · Interval/dispersion: Full Range
Group
Value
Spread
Lower
Upper
Comment
Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemotherapy
5389.0
Not reported
2582.7
20724.3
Not reported
Phase 2 (Pivotal Study): Cohort 1
11309.5
Not reported
2282.3
39818.9
Not reported
Phase 2 (Pivotal Study): Cohort 2
8278.7
Not reported
2332.6
31857.7
Not reported
Phase 2 (Safety Management Study): Cohort 3
15411.9
Not reported
4327.4
30575.9
Not reported
TNF alpha
Values in pg/mL · Interval/dispersion: Full Range
Group
Value
Spread
Lower
Upper
Comment
Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemotherapy
10.5
Not reported
1.8
443.1
Not reported
Phase 2 (Pivotal Study): Cohort 1
8.6
Not reported
2.6
166.9
Not reported
Phase 2 (Pivotal Study): Cohort 2
6.8
Not reported
2.2
44.9
Not reported
Phase 2 (Safety Management Study): Cohort 3
10.9
Not reported
3.3
52.1
Not reported
VCAM-1
Values in pg/mL · Interval/dispersion: Full Range
Group
Value
Spread
Lower
Upper
Comment
Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemotherapy
1387033.6
Not reported
609223.2
8424222.9
Not reported
Phase 2 (Pivotal Study): Cohort 1
1478356.8
Not reported
642372.6
3859375.8
Not reported
Phase 2 (Pivotal Study): Cohort 2
1058453.9
Not reported
634769.7
2864040.2
Not reported
Phase 2 (Safety Management Study): Cohort 3
1367940.7
Not reported
721050.0
5184238.4
Not reported
Complete source fields
classes
categories
measurements
group Id
OG000
lower Limit
147.0
upper Limit
2000.0
value
2000.0
group Id
OG001
lower Limit
628.1
upper Limit
2000.0
value
2000.0
group Id
OG002
lower Limit
434.2
upper Limit
2000.0
value
2000.0
group Id
OG003
lower Limit
541.0
upper Limit
2000.0
value
2000.0
title
IP-10
categories
measurements
group Id
OG000
lower Limit
0.6
upper Limit
463.8
value
33.1
group Id
OG001
lower Limit
1.0
upper Limit
3306.0
value
31.1
group Id
OG002
lower Limit
1.0
upper Limit
406.8
value
17.3
group Id
OG003
lower Limit
1.0
upper Limit
534.6
value
44.1
title
Granzyme B
categories
measurements
group Id
OG000
lower Limit
537796.8
upper Limit
2424877.7
value
792754.3
group Id
OG001
lower Limit
557025.0
upper Limit
7495123.2
value
1322829.3
group Id
OG002
lower Limit
544589.3
upper Limit
4588974.8
value
989188.4
group Id
OG003
lower Limit
256768.6
upper Limit
4879749.7
value
1009966.4
title
ICAM-1
categories
measurements
group Id
OG000
lower Limit
81.1
upper Limit
1876.0
value
792.0
group Id
OG001
lower Limit
32.4
upper Limit
1876.0
value
493.8
group Id
OG002
lower Limit
7.5
upper Limit
1876.0
value
364.9
group Id
OG003
lower Limit
65.0
upper Limit
1876.0
value
1857.2
title
IFN-gamma
categories
measurements
group Id
OG000
lower Limit
544.3
upper Limit
4000.0
value
2173.3
group Id
OG001
lower Limit
510.8
upper Limit
4000.0
value
2371.2
group Id
OG002
lower Limit
649.9
upper Limit
4000.0
value
1999.9
group Id
OG003
lower Limit
653.7
upper Limit
4000.0
value
2160.5
title
IL-1 RA
categories
measurements
group Id
OG000
lower Limit
3.1
upper Limit
91.0
value
18.4
group Id
OG001
lower Limit
0.9
upper Limit
123.1
value
25.0
group Id
OG002
lower Limit
0.9
upper Limit
63.7
value
13.4
group Id
OG003
lower Limit
0.9
upper Limit
189.4
value
20.0
title
IL-2
categories
measurements
group Id
OG000
lower Limit
2189.0
upper Limit
34044.5
value
16872.7
group Id
OG001
lower Limit
78.0
upper Limit
100000.0
value
14383.7
group Id
OG002
lower Limit
78.0
upper Limit
66024.6
value
7817.3
group Id
OG003
lower Limit
3002.6
upper Limit
100000.0
value
12386.4
title
IL-2 R alpha
categories
measurements
group Id
OG000
lower Limit
2.4
upper Limit
976.0
value
305.3
group Id
OG001
lower Limit
3.5
upper Limit
976.0
value
89.4
group Id
OG002
lower Limit
3.6
upper Limit
976.0
value
44.6
group Id
OG003
lower Limit
13.3
upper Limit
976.0
value
921.8
title
IL-6
categories
measurements
group Id
OG000
lower Limit
31.2
upper Limit
71.5
value
51.5
group Id
OG001
lower Limit
13.8
upper Limit
153.5
value
38.9
group Id
OG002
lower Limit
27.9
upper Limit
98.8
value
44.1
group Id
OG003
lower Limit
19.1
upper Limit
83.8
value
38.8
title
IL-7
categories
measurements
group Id
OG000
lower Limit
17.1
upper Limit
750.0
value
86.4
group Id
OG001
lower Limit
14.2
upper Limit
750.0
value
118.4
group Id
OG002
lower Limit
9.8
upper Limit
750.0
value
77.2
group Id
OG003
lower Limit
10.3
upper Limit
750.0
value
120.9
title
IL-8
categories
measurements
group Id
OG000
lower Limit
3.8
upper Limit
614.0
value
52.5
group Id
OG001
lower Limit
0.7
upper Limit
466.0
value
43.9
group Id
OG002
lower Limit
0.7
upper Limit
263.6
value
18.8
group Id
OG003
lower Limit
1.8
upper Limit
466.0
value
48.2
title
IL-10
categories
measurements
group Id
OG000
lower Limit
18.7
upper Limit
271.3
value
57.1
group Id
OG001
lower Limit
13.1
upper Limit
226.6
value
56.5
group Id
OG002
lower Limit
11.3
upper Limit
195.2
value
47.6
group Id
OG003
lower Limit
21.9
upper Limit
537.3
value
50.3
title
IL-15
denoms
counts
group Id
OG000
value
7
group Id
OG001
value
77
group Id
OG002
value
24
group Id
OG003
value
38
units
Participants
description
Peak was defined as the maximum post-baseline level of the cytokine. Following key cytokines were measured: interferon-gamma induced protein 10 (IP-10), ferritin, granzyme B, intercellular adhesion molecule (ICAM-1), interferon-gamma (IFN-gamma), interleukin-1 receptor antagonist (IL-1RA), IL-2, interleukin-2 receptor alpha (IL-2 R alpha), IL-6, IL-7, IL-8, IL-10, IL-15, perforin, tumor necrosis factor alpha (TNF alpha), and vascular cell adhesion molecule- 1 (VCAM-1).
dispersion Type
Full Range
groups
description
Participants with diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), or transformed follicular lymphoma (TFL) received conditioning chemotherapy (fludarabine 30 mg/m\^2 intravenously \[IV\] over 30 minutes and cyclophosphamide 500 mg/m\^2 IV over 60 minutes) on Days -5, -4, and -3; followed by a single infusion of axicabtagene ciloleucel chimeric antigen receptor (CAR) transduced autologous T cells administered IV at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg of body weight (BW) on Day 0.
id
OG000
title
Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemotherapy
description
Participants with refractory DLBCL received conditioning chemotherapy (fludarabine 30 mg/m\^2 IV over 30 minutes and cyclophosphamide 500 mg/m\^2 IV over 60 minutes) on Days -5, -4, and -3; followed by a single infusion of axicabtagene ciloleucel CAR transduced autologous T cells administered IV at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg of BW on Day 0.
id
OG001
title
Phase 2 (Pivotal Study): Cohort 1
description
Participants with refractory PMBCL or TFL received conditioning chemotherapy (fludarabine 30 mg/m\^2 IV over 30 minutes and cyclophosphamide 500 mg/m\^2 IV over 60 minutes) on Days -5, -4, and -3; followed by a single infusion of axicabtagene ciloleucel CAR transduced autologous T cells administered IV at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg of BW on Day 0..
id
OG002
title
Phase 2 (Pivotal Study): Cohort 2
description
Participants with relapsed or refractory transplant ineligible DLBCL, PMBCL, or TFL received conditioning chemotherapy (fludarabine 30 mg/m\^2 IV over 30 minutes and cyclophosphamide 500 mg/m\^2 IV over 60 minutes) on Days -5, -4, and -3; followed by a single infusion of axicabtagene ciloleucel CAR transduced autologous T cells administered IV at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg of BW on Day 0. Participants also received a prophylactic regimen of levetiracetam (750 mg orally or IV twice daily (BID) starting on Day 0) and tocilizumab (8 mg/kg IV over 1 hour (not to exceed 800 mg)) on Day 2).
id
OG003
title
Phase 2 (Safety Management Study): Cohort 3
param Type
MEDIAN
population Description
Participants in the Safety Analysis Set were analyzed.
reporting Status
POSTED
time Frame
Baseline up to Month 3
title
Pharmacodynamics: Peak Level of Cytokines in Serum (Phase 1 and Phase 2 Cohorts 1, 2, and 3)
Triangle