Long-Term Follow-Up of Bridging Therapies Prior to CAR T-Cell Therapy for Relapsed/Refractory Large B Cell Lymphoma
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patient Selection
2.2. Bridging Therapy and CAR T Infusion
2.3. Toxicity Evaluation
2.4. Risk Factor Definition
2.5. Study end Points and Statistical Methods
3. Results
3.1. Patient Details
3.2. Hemato-Oncologic Outcomes
3.3. Treatment Related Toxicities
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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BT | p | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Characteristic | All Patients (n = 156) | No BT (n = 74) | BT (n = 82) | ST (n = 63) | CMT (n = 7) | RT (n = 12) | No BT vs. BT | ST vs. No BT | ST vs. CMT | ST vs. RT | No BT vs. CMT | No BT vs. RT | CMT vs. RT |
Age (median [range]) | 62.0 (21–84) | 61.0 (22–80) | 62.5 (21–84) | 62.0 (23–84) | 64.0 (25–71) | 65.0 (21–75) | 0.896 | 0.856 | 0.744 | 0.965 | 0.798 | 0.889 | 0.819 |
>60 | 88 (56.4%) | 38 (51.4%) | 50 (61.0%) | 38 (60.3%) | 5 (71.4%) | 7 (58.3%) | 0.294 | 0.379 | 0.87 | 1 | 0.534 | 0.891 | 0.938 |
Male | 97 (62.2%) | 47 (63.5%) | 50 (61.0%) | 41 (65.1%) | 4 (57.1%) | 5 (41.7%) | 0.872 | 0.991 | 1 | 0.229 | 1 | 0.264 | 0.861 |
Race and Ethnicity | 0.121 | 0.137 | 0.264 | 0.675 | 0.637 | 0.052 | 0.086 | ||||||
Asian | 35 (22.4%) | 10 (13.5%) | 25 (30.5%) | 19 (30.2%) | 0 (0.0%) | 6 (50.0%) | |||||||
Black | 8 (5.1%) | 4 (5.4%) | 4 (4.9%) | 3 (4.8%) | 1 (14.3%) | 0 (0.0%) | |||||||
Hispanic White | 38 (24.4%) | 19 (25.7%) | 19 (23.2%) | 16 (25.4%) | 1 (14.3%) | 2 (16.7%) | |||||||
Native Hawaiian or other Pacific Islander | 1 (0.6%) | 0 (0.0%) | 1 (1.2%) | 1 (1.6%) | 0 (0.0%) | 0 (0.0%) | |||||||
Non-Hispanic White | 73 (46.8%) | 40 (54.1%) | 33 (40.2%) | 24 (38.1%) | 5 (71.4%) | 4 (33.3%) | |||||||
Unknown | 1 (0.6%) | 1 (1.4%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | |||||||
ECOG PS 2–3 | 6 (3.8%) | 1 (1.4%) | 5 (6.1%) | 1 (1.6%) | 1 (14.3%) | 3 (25.0%) | 0.262 | 1 | 0.473 | 0.009 | 0.404 | 0.004 | 1 |
Stage III/IV | 109 (69.9%) | 46 (62.2%) | 63 (76.8%) | 49 (77.8%) | 7 (100.0%) | 7 (58.3%) | 0.069 | 0.073 | 0.37 | 0.29 | 0.11 | 1 | 0.147 |
Extranodal disease | 104 (66.7%) | 47 (63.5%) | 57 (69.5%) | 43 (68.3%) | 7 (100.0%) | 7 (58.3%) | 0.533 | 0.688 | 0.186 | 0.738 | 0.124 | 0.982 | 0.147 |
>1 Site Extranodal disease | 81 (51.9%) | 39 (52.7%) | 42 (51.2%) | 31 (49.2%) | 7 (100.0%) | 4 (33.3%) | 0.98 | 0.813 | 0.031 | 0.487 | 0.044 | 0.351 | 0.018 |
IPI | 0.02 | 0.021 | 0.619 | 0.154 | 0.013 | 0.126 | 0.316 | ||||||
IPI ≥ 3 | 16 (10.3%) | 2 (2.7%) | 14 (17.1%) | 10 (15.9%) | 2 (28.6%) | 2 (16.7%) | 0.007 | 0.016 | 0.751 | 1 | 0.035 | 0.164 | 0.976 |
Pathology | 0.202 | 0.439 | 0.891 | 0.287 | 0.73 | 0.149 | 0.607 | ||||||
DLBCL | 107 (68.6%) | 47 (63.5%) | 60 (73.2%) | 44 (69.8%) | 5 (71.4%) | 11 (91.7%) | |||||||
PMBCL | 8 (5.1%) | 6 (8.1%) | 2 (2.4%) | 2 (3.2%) | 0 (0.0%) | 0 (0.0%) | |||||||
tFL | 41 (26.3%) | 21 (28.4%) | 20 (24.4%) | 17 (27.0%) | 2 (28.6%) | 1 (8.3%) | |||||||
Cell of Origin | 0.678 | 0.797 | 0.727 | 0.285 | 0.738 | 0.278 | 0.917 | ||||||
ABC | 54 (34.6%) | 23 (31.1%) | 31 (37.8%) | 22 (34.9%) | 3 (42.9%) | 6 (50.0%) | |||||||
GCB | 86 (55.1%) | 43 (58.1%) | 43 (52.4%) | 36 (57.1%) | 3 (42.9%) | 4 (33.3%) | |||||||
HGBL-DH/TH | 24 (15.4%) | 9 (12.2%) | 15 (18.3%) | 11 (17.5%) | 3 (42.9%) | 1 (8.3%) | 0.402 | 0.527 | 0.273 | 0.718 | 0.103 | 1 | 0.231 |
Double Expresser | 26 (16.7%) | 14 (18.9%) | 12 (14.6%) | 7 (11.1%) | 1 (14.3%) | 4 (33.3%) | 0.616 | 0.305 | 1 | 0.121 | 1 | 0.45 | 0.712 |
Max Dimension (mm; median [range]) | 50.0 (5.0–212.0) | 38.0 (5.0–122.0) | 54.0 (10.0–212.0) | 55.0 (10.0–212.0) | 69.0 (14.0–137.0) | 52.0 (13.0–122.0) | <0.001 | <0.001 | <0.001 | 0.55 | <0.001 | <0.001 | <0.001 |
Bulky Disease (≥7.5 cm) | 40 (25.6%) | 16 (21.6%) | 24 (29.3%) | 18 (28.6%) | 4 (57.1%) | 2 (16.7%) | 0.364 | 0.459 | 0.265 | 0.618 | 0.104 | 0.993 | 0.187 |
Large Disease (≥5 cm) | 75 (48.1%) | 28 (37.8%) | 47 (57.3%) | 37 (58.7%) | 3 (42.9%) | 7 (58.3%) | 0.023 | 0.023 | 0.687 | 1 | 1 | 0.306 | 0.861 |
LDH | 0.006 | 0.002 | 0.21 | 0.542 | 0.596 | 0.648 | 0.645 | ||||||
>ULN and <2xULN | 53 (34.0%) | 17 (23.0%) | 36 (43.9%) | 31 (49.2%) | 1 (14.3%) | 4 (33.3%) | |||||||
LDH > 2xULN | 12 (7.7%) | 4 (5.4%) | 8 (9.8%) | 6 (9.5%) | 1 (14.3%) | 1 (8.3%) | 0.473 | 0.552 | 1 | 1 | 0.911 | 1 | 1 |
Maximum SUV (median [range]) | 16.0 (1.4–56.6) | 14.8 (2.4–56.6) | 16.9 (1.4–40.0) | 17.0 (1.4–40.0) | 15.7 (12.8–21.6) | 17.4 (4.8–34.8) | <0.001 | <0.001 | 0.711 | 0.576 | <0.001 | <0.001 | 0.477 |
Maximum SUV > 10 | 118 (75.6%) | 52 (70.3%) | 66 (80.5%) | 50 (79.4%) | 7 (100.0%) | 9 (75.0%) | 0.194 | 0.308 | 0.412 | 1 | 0.213 | 1 | 0.43 |
Number of Lesions (median [range]) | 5.0 (1–109) | 4.5 (1–60) | 5.0 (1–109) | 5.0 (1–109) | 7.0 (6–16) | 3.0 (1–20) | 0.275 | 0.186 | 0.841 | 0.333 | 0.617 | 0.494 | 0.104 |
Lines of prior therapy, n (median [range]) | 2.0 (2–8) | 3.0 (2–6) | 2.0 (2–8) | 2.0 (2–6) | 2.0 (2–8) | 2.0 (2–5) | 0.283 | 0.156 | 0.262 | 0.742 | 0.589 | 0.667 | 0.611 |
Lines of prior therapy ≥ 3 | 76 (48.7%) | 41 (55.4%) | 35 (42.7%) | 27 (42.9%) | 3 (42.9%) | 5 (41.7%) | 0.154 | 0.196 | 1 | 1 | 0.81 | 0.567 | 1 |
Axi-cell CAR T Product | 153 (98.1%) | 73 (98.6%) | 80 (97.6%) | 61 (96.8%) | 7 (100.0%) | 12 (100.0%) | 1 | 0.888 | 1 | 1 | 1 | 1 | 1 |
Leukapheresis to CAR T infusion interval, d (median [range]) | 27.0 (20–242) | 27.0 (20–183) | 27.0 (20–242) | 27.0 (20–57) | 27.0 (21–35) | 27.0 (24–242) | 0.73 | 0.18 | 0.858 | 0.023 | 0.613 | 0.142 | 0.449 |
Patient | Comprehensive or Focal RT | # of Sites on PET | RT Dose (Gy) | RT Fractions | RT Target | Concurrent Systemic Therapy | Pattern of Failure |
---|---|---|---|---|---|---|---|
Patient 1 | Focal | 7 | 20 | 5 | R neck/mediastinum | R-ICE | Out of field |
Patient 2 | Comprehensive | 1 | 4 | 2 | Right foot | None | Death without recurrence |
Patient 3 | Comprehensive | 2 | 4 40 | 2 20 | Left tonsil Head and neck | None | None |
Patient 4 | Comprehensive | 1 | 14 | 7 | Right lateral chest wall | None | None |
Patient 5 | Focal | 6 | 30 | 10 | L2-S5 | Dexamethasone, intrathecal cytarabine and methotrexate | Out of field |
Patient 6 | Comprehensive | 3 | 24 | 12 | Head and neck | None | None |
Patient 7 | Focal | 16 | 29.6 20 20 14 | 16 7 7 10 | Abdomen/pelvis T11 paravertebral One iliac nodes RT humerus | Dexamethasone, pembrolizumab | In field |
Patient 8 | Focal | 7 | 20 | 5 | Abdomen | R-BENDA-POLA | Out of field |
Patient 9 | Focal | 10 | 30 20 | 10 5 | Right chest wall Right lower abdomen | R-BENDA-POLA | Out of field |
Patient 10 | Comprehensive | 5 | 24.75 20 | 11 10 | Right neck Retroperitoneum | None | None |
Patient 11 | Comprehensive | 2 | 30 | 10 | Bilateral head and neck | None | Death without recurrence |
Patient 12 | Focal | 5 | 15 | 5 | Left supraclavicular area | None | None |
Patient 13 | Comprehensive | 3 | 9 7.5 12.5 15 30 | 3 3 5 5 10 | Left thigh Right breast Right breast Right knee Left leg | None | None |
Patient 14 | Comprehensive | 2 | 30 | 10 | Left neck | None | None |
Patient 15 | Focal | 6 | 20 | 10 | R foot | None | Out of field |
Patient 16 | Focal | 8 | 21 20 20 | 10 10 10 | Left neck Right neck Left thigh | R-BENDA-POLA | In field |
Patient 17 | Focal | 20 | 20 20 | 10 10 | Head and neck axilla | None | Out of field |
Patient 18 | Focal | 6 | 30 | 10 | Right calf | R-BENDA-POLA | In field |
Patient 19 | Focal | 7 | 15 | 5 | Sinus | None | Out of field |
BT | p | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Characteristic | All Patients (n = 156) | No BT (n = 74) | BT (n = 82) | ST (n = 63) | CMT (n = 7) | RT (n = 12) | No BT vs. BT | ST vs. No BT | ST vs. CMT | ST vs. RT | No BT vs. CMT | No BT vs. RT | CMT vs. RT |
Best Response | 0.51 | 0.61 | 0.163 | 0.663 | 0.065 | 0.917 | 0.139 | ||||||
CR | 101 (65.2%) | 51 (68.9%) | 50 (61.0%) | 39 (61.9%) | 2 (28.6%) | 9 (75.0%) | |||||||
PD | 15 (9.7%) | 6 (8.1%) | 9 (11.0%) | 6 (9.5%) | 2 (28.6%) | 1 (8.3%) | |||||||
PR | 39 (25.2%) | 16 (21.6%) | 23 (28.0%) | 18 (28.6%) | 3 (42.9%) | 2 (16.7%) | |||||||
ORR | 140 (90.3%) | 67 (90.5%) | 73 (89.0%) | 52 (82.5%) | 5 (71.4%) | 8 (66.7%) | 0.759 | 0.441 | 0.838 | 0.386 | 1 | 0.759 | 1 |
CRR | 101 (65.2%) | 51 (68.9%) | 50 (61.0%) | 36 (57.1%) | 2 (28.6%) | 8 (66.7%) | 0.322 | 0.975 | 0.298 | 0.769 | 0.335 | 0.677 | 0.259 |
OS, years | 0.158 | 0.183 | 0.04 | 0.38 | 0.001 | 0.707 | 0.021 | ||||||
Median | 3.16 | NR | 3.16 | 3.16 | 0.54 | 3.32 | |||||||
95% CI | 2.09—NR | 2.33—NR | 1.37—NR | 1.33—NR | 0.02—NR | 1.17–3.32 | |||||||
PFS, years | 0.16 | 0.176 | 0.004 | 0.144 | <0.001 | 0.376 | 0.001 | ||||||
Median | 1.05 | 1.45 | 0.65 | 0.65 | 0.24 | 3.32 | |||||||
95% CI | 0.55–1.95 | 0.58—NR | 0.28–1.79 | 0.28–1.79 | 0.02–0.45 | 0.13–3.32 | |||||||
CRS ≥ 1 | 133 (85.3%) | 58 (78.4%) | 75 (91.5%) | 58 (92.1%) | 5 (71.4%) | 12 (100.0%) | 0.038 | 0.048 | 0.288 | 0.705 | 1 | 0.166 | 0.237 |
CRS ≥ 3 | 11 (7.1%) | 5 (6.8%) | 6 (7.3%) | 3 (4.8%) | 1 (14.3%) | 2 (16.7%) | 1 | 0.896 | 0.864 | 0.377 | 1 | 0.551 | 1 |
ICANS ≥ 1 | 68 (43.6%) | 31 (41.9%) | 37 (45.1%) | 28 (44.4%) | 4 (57.1%) | 5 (41.7%) | 0.807 | 0.898 | 0.81 | 1 | 0.704 | 1 | 0.861 |
ICANS ≥ 3 | 18 (11.5%) | 7 (9.5%) | 11 (13.4%) | 7 (11.1%) | 2 (28.6%) | 2 (16.7%) | 0.602 | 0.972 | 0.475 | 0.954 | 0.363 | 0.804 | 0.976 |
Steroid Administration | 62 (39.7%) | 31 (41.9%) | 31 (37.8%) | 22 (34.9%) | 3 (42.9%) | 6 (50.0%) | 0.721 | 0.51 | 1 | 0.507 | 1 | 0.832 | 1 |
Tocilizumab Administration | 93 (59.6%) | 42 (56.8%) | 51 (62.2%) | 39 (61.9%) | 3 (42.9%) | 9 (75.0%) | 0.598 | 0.662 | 0.569 | 0.591 | 0.757 | 0.381 | 0.364 |
ICU Admission | 11 (7.1%) | 5 (6.8%) | 6 (7.3%) | 4 (6.3%) | 0 (0.0%) | 2 (16.7%) | 1 | 1 | 1 | 0.531 | 1 | 0.551 | 0.714 |
Characteristic | All Patients (n = 19) | Focal (n = 11) | Comprehensive (n = 8) | p |
---|---|---|---|---|
Age (median [range]) | 64.0 (21–75) | 66.0 (21–73) | 58.0 (41–75) | 0.888 |
>60 | 12 (63.2%) | 8 (72.7%) | 4 (50.0%) | 0.594 |
Male | 9 (47.4%) | 4 (36.4%) | 5 (62.5%) | 0.508 |
Race and Ethnicity | 0.592 | |||
Asian | 6 (31.6%) | 3 (27.3%) | 3 (37.5%) | |
Black | 1 (5.3%) | 1 (9.1%) | 0 (0.0%) | |
Hispanic White | 3 (15.8%) | 1 (9.1%) | 2 (25.0%) | |
Non-Hispanic White | 9 (47.4%) | 6 (54.5%) | 3 (37.5%) | |
ECOG PS 2–3 | 4 (21.1%) | 3 (27.3%) | 1 (12.5%) | 0.834 |
Stage III/IV | 14 (73.7%) | 10 (90.9%) | 4 (50.0%) | 0.141 |
Extranodal disease | 14 (73.7%) | 10 (90.9%) | 4 (50.0%) | 0.141 |
>1 Site Extranodal disease | 11 (57.9%) | 10 (90.9%) | 1 (12.5%) | 0.003 |
IPI | 0.225 | |||
IPI ≥ 3 | 4 (21.1%) | 3 (27.3%) | 1 (12.5%) | 0.834 |
Pathology | 1 | |||
DLBCL | 16 (84.2%) | 9 (81.8%) | 7 (87.5%) | |
tFL | 3 (15.8%) | 2 (18.2%) | 1 (12.5%) | |
Cell of Origin | 0.598 | |||
ABC | 9 (47.4%) | 6 (54.5%) | 3 (37.5%) | |
GCB | 7 (36.8%) | 3 (27.3%) | 4 (50.0%) | |
Unknown | 3 (15.8%) | 2 (18.2%) | 1 (12.5%) | |
HGBL-DH/TH | 4 (21.1%) | 3 (27.3%) | 1 (12.5%) | 0.834 |
Double Expresser | 5 (26.3%) | 3 (27.3%) | 2 (25.0%) | 1 |
Max Dimension (mm; median [range]) | 52.0 (13.0–137.0) | 66.0 (14.0–137.0) | 49.0 (13.0–82.0) | <0.001 |
Bulky Disease (≥7.5 cm) | 6 (31.6%) | 5 (45.5%) | 1 (12.5%) | 0.305 |
Large Disease (≥5 cm) | 10 (52.6%) | 6 (54.5%) | 4 (50.0%) | 1 |
LDH | 0.092 | |||
>ULN and <2xULN | 5 (26.3%) | 1 (9.1%) | 4 (50.0%) | |
>2xULN | 2 (10.5%) | 2 (18.2%) | 0 (0.0%) | |
LDH > 2xULN | 2 (10.5%) | 2 (18.2%) | 0 (0.0%) | 0.604 |
Maximum SUV (median [range]) | 16.5 (4.8–34.8) | 15.7 (4.8–22.1) | 23.4 (9.5–34.8) | 0.063 |
Maximum SUV > 10 | 16 (84.2%) | 10 (90.9%) | 6 (75.0%) | 0.763 |
Number of Lesions (median [range]) | 6.0 (1–20) | 7.0 (5–20) | 2.0 (1–5) | 0.002 |
Lines of prior therapy, n (median [range]) | 2.0 (2–8) | 2.0 (2–8) | 2.0 (2–5) | 0.964 |
Lines of prior therapy ≥ 3 | 8 (42.1%) | 5 (45.5%) | 3 (37.5%) | 1 |
Axi-cell CAR T product | 19 (100.0%) | 11 (100.0%) | 8 (100%) | 1 |
Leukapheresis to CAR T infusion interval, d (median [range]) | 27.0 (21–242) | 27.0 (21–35) | 27.5 (26–242) | 0.214 |
Category | OR | −95% CI | +95% CI | p |
---|---|---|---|---|
CRS ≥ Grade 1 | ||||
Lines of prior therapy, n | 0.632 | 0.432 | 0.925 | 0.018 |
Bridging Therapy | ||||
No BT | Ref | |||
BT | 2.792 | 1.047 | 7.45 | 0.04 |
>1 Lesions | 3.172 | 1.077 | 9.349 | 0.036 |
CRS ≥ Grade 3 | ||||
LDH > 2xULN | 5.949 | 1.32 | 26.802 | 0.02 |
Disease Sites | 1.028 | 1 | 1.056 | 0.049 |
ICANS ≥ Grade 1 | ||||
CRS | 10.343 | 2.332 | 45.88 | 0.002 |
ICANS ≥ Grade 3 | ||||
LDH > 2xULN | 4.643 | 1.239 | 17.394 | 0.023 |
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Share and Cite
Ladbury, C.; Dandapani, S.; Hao, C.; Fabros, M.; Amini, A.; Sampath, S.; Glaser, S.; Sokolov, K.; Yeh, J.; Baird, J.H.; et al. Long-Term Follow-Up of Bridging Therapies Prior to CAR T-Cell Therapy for Relapsed/Refractory Large B Cell Lymphoma. Cancers 2023, 15, 1747. https://doi.org/10.3390/cancers15061747
Ladbury C, Dandapani S, Hao C, Fabros M, Amini A, Sampath S, Glaser S, Sokolov K, Yeh J, Baird JH, et al. Long-Term Follow-Up of Bridging Therapies Prior to CAR T-Cell Therapy for Relapsed/Refractory Large B Cell Lymphoma. Cancers. 2023; 15(6):1747. https://doi.org/10.3390/cancers15061747
Chicago/Turabian StyleLadbury, Colton, Savita Dandapani, Claire Hao, Mildred Fabros, Arya Amini, Sagus Sampath, Scott Glaser, Karen Sokolov, Jekwon Yeh, John H. Baird, and et al. 2023. "Long-Term Follow-Up of Bridging Therapies Prior to CAR T-Cell Therapy for Relapsed/Refractory Large B Cell Lymphoma" Cancers 15, no. 6: 1747. https://doi.org/10.3390/cancers15061747