Clinical characteristics of patients with 2 distinct IRs after CD19-directed CAR-T therapy, split based on biopsy confirmation
| . | SLR . | HR . | ||||
|---|---|---|---|---|---|---|
| Total (n = 11∗) . | Confirmed by biopsy (n = 5∗) . | Not confirmed by biopsy (n = 6∗) . | Total (n = 9∗) . | Confirmed by biopsy (n = 3) . | Not confirmed by biopsy (n = 6∗) . | |
| Median age†, y (range) | 61 (35-73) | 61 (35-73) | 61 (46-72) | 58 (47-66) | 52 (47-66) | 59 (54-66) |
| Male sex†, n (%) | 7 (64) | 2 (40) | 5 (83) | 7 (78) | 2 (67) | 5 (83) |
| Histological subtype† , n (%) | ||||||
| DLBCL | 8 (73) | 4 (80) | 4 (67) | 6 (67) | 1 (33) | 5 (83) |
| tFL | 2 (18) | 1 (20) | 1 (17) | 3 (33) | 2 (67) | 1 (17) |
| MCL | 1 (9) | — | 1 (17) | — | — | — |
| Ann Arbor stage† , n (%) | ||||||
| I-II | 1 (10) | — | 1 (17) | 2 (22) | 1 (33) | 1 (17) |
| III-IV | 10 (90) | 5 (100) | 5 (83) | 7 (78) | 2 (67) | 5 (83) |
| Prior lines of systemic therapy† , n (%) | ||||||
| 1 | 2 (18) | 2 (40) | — | 1 (11) | — | 1 (17) |
| 2 | 7 (64) | 3 (60) | 4 (67) | 6 (67) | 2 (67) | 4 (67) |
| ≥3 | 2 (18) | — | 2 (33) | 2 (18) | 1 (33) | 1 (17) |
| Prior stem cell transplantation† , n (%) | ||||||
| No | 8 (73) | 4 (80) | 4 (67) | 9 (100) | 3 (100) | 6 (100) |
| Auto-SCT | 3 (27) | 1 (20) | 2 (33) | — | — | — |
| Allo-SCT | — | — | — | — | — | — |
| Bridging strategy, n (%) | ||||||
| No bridging | 6 (55) | 5 (100) | 1 (17) | 4 (44) | 1 (3) | 3 (50) |
| Systemic therapy | 2 (18) | — | 2 (33) | — | — | — |
| RT | 1 (9) | — | 1 (17) | 5 (56) | 2 (67) | 3 (50) |
| Best response to CAR-T therapy, n (%) | ||||||
| CMR | 10 (90) | 5 (100) | 5 (83) | 7 (78) | 3 (100) | 4 (67) |
| PMR | 1 (10) | — | 1 (17) | 2 (22) | — | 2 (33) |
| Response to CAR-T therapy at last assessment, n (%) | ||||||
| CMR | 9 (82) | 5 (100) | 4 (67) | 6 (67) | 2 (67) | 4 (67) |
| PMR | 1 (9) | — | 1 (17) | 2 (22) | — | 2 (33) |
| PD | 1 (9) | — | 1 (17) | 1 (11) | 1 (33) | — |
| Median follow-up from the onset of IR (d), median (range) | 755 (133-1558) | 1140 (949-1558) | 530 (133-755) | 550 (180-1397) | 584 (383-1126) | 396.5 (180-1397) |
| Time between CAR-T infusion and onset of IR (d), median (range) | 116 (–259 to 548) | 184 (–259 to 268) | 70.5 (–105 to 548) | 28 (21-31) | 28 (28-29) | 28 (21-31) |
| Time between IR onset and resolution (d), median(range) | 190 (13-585) | 459 (187-494) | 181 (13-585) | 141 (102-427) | 284 (141-427) | 102 (—) |
| Ongoing, n (%) | 3 (27) | 2 (40) | 1 (17) | 6 (67) | 1 (33) | 5 (83) |
| Duration if ongoing (d), median (range) | 989 (402-1321) | 1155 (989-1321) | 402 (—) | 285.5 (85-1035) | 329 (—) | 242 (85-1035) |
| Any B symptoms reported at the time of onset of IR | ||||||
| Yes, n (%) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| Missing, n (%) | 1 (9) | 1 (20) | — | 0 (0) | — | — |
| LDH levels at the time of onset of IR, n (%) | ||||||
| ≤ULN | 5 (45) | 3 (60) | 2 (33) | 6 (67) | 1 (33) | 5 (83) |
| >ULN | 3 (27) | — | 3 (50) | 3 (33) | 2 (67) | 1 (17) |
| >2 × ULN | — | — | — | — | — | — |
| Missing, n (%) | 3 (27) | 2 (40) | 1 (17) | — | — | — |
| CRP at time of onset of IR, median (range) | 3.3 (1.1-7) | 2.5 (1.7-3.3) | 4.5 (1.1-7) | 1.5 (0.3-53) | 0.9 (0.7-43) | 2 (0.3-53) |
| Missing, n (%) | 6 (55) | 3 (60) | 3 (50) | 1 (11) | — | 1 (17) |
| IR in irradiated field if patient received RT, yes, n (%) | — | — | — | 5 (100) | 2 (100) | 3 (100) |
| . | SLR . | HR . | ||||
|---|---|---|---|---|---|---|
| Total (n = 11∗) . | Confirmed by biopsy (n = 5∗) . | Not confirmed by biopsy (n = 6∗) . | Total (n = 9∗) . | Confirmed by biopsy (n = 3) . | Not confirmed by biopsy (n = 6∗) . | |
| Median age†, y (range) | 61 (35-73) | 61 (35-73) | 61 (46-72) | 58 (47-66) | 52 (47-66) | 59 (54-66) |
| Male sex†, n (%) | 7 (64) | 2 (40) | 5 (83) | 7 (78) | 2 (67) | 5 (83) |
| Histological subtype† , n (%) | ||||||
| DLBCL | 8 (73) | 4 (80) | 4 (67) | 6 (67) | 1 (33) | 5 (83) |
| tFL | 2 (18) | 1 (20) | 1 (17) | 3 (33) | 2 (67) | 1 (17) |
| MCL | 1 (9) | — | 1 (17) | — | — | — |
| Ann Arbor stage† , n (%) | ||||||
| I-II | 1 (10) | — | 1 (17) | 2 (22) | 1 (33) | 1 (17) |
| III-IV | 10 (90) | 5 (100) | 5 (83) | 7 (78) | 2 (67) | 5 (83) |
| Prior lines of systemic therapy† , n (%) | ||||||
| 1 | 2 (18) | 2 (40) | — | 1 (11) | — | 1 (17) |
| 2 | 7 (64) | 3 (60) | 4 (67) | 6 (67) | 2 (67) | 4 (67) |
| ≥3 | 2 (18) | — | 2 (33) | 2 (18) | 1 (33) | 1 (17) |
| Prior stem cell transplantation† , n (%) | ||||||
| No | 8 (73) | 4 (80) | 4 (67) | 9 (100) | 3 (100) | 6 (100) |
| Auto-SCT | 3 (27) | 1 (20) | 2 (33) | — | — | — |
| Allo-SCT | — | — | — | — | — | — |
| Bridging strategy, n (%) | ||||||
| No bridging | 6 (55) | 5 (100) | 1 (17) | 4 (44) | 1 (3) | 3 (50) |
| Systemic therapy | 2 (18) | — | 2 (33) | — | — | — |
| RT | 1 (9) | — | 1 (17) | 5 (56) | 2 (67) | 3 (50) |
| Best response to CAR-T therapy, n (%) | ||||||
| CMR | 10 (90) | 5 (100) | 5 (83) | 7 (78) | 3 (100) | 4 (67) |
| PMR | 1 (10) | — | 1 (17) | 2 (22) | — | 2 (33) |
| Response to CAR-T therapy at last assessment, n (%) | ||||||
| CMR | 9 (82) | 5 (100) | 4 (67) | 6 (67) | 2 (67) | 4 (67) |
| PMR | 1 (9) | — | 1 (17) | 2 (22) | — | 2 (33) |
| PD | 1 (9) | — | 1 (17) | 1 (11) | 1 (33) | — |
| Median follow-up from the onset of IR (d), median (range) | 755 (133-1558) | 1140 (949-1558) | 530 (133-755) | 550 (180-1397) | 584 (383-1126) | 396.5 (180-1397) |
| Time between CAR-T infusion and onset of IR (d), median (range) | 116 (–259 to 548) | 184 (–259 to 268) | 70.5 (–105 to 548) | 28 (21-31) | 28 (28-29) | 28 (21-31) |
| Time between IR onset and resolution (d), median(range) | 190 (13-585) | 459 (187-494) | 181 (13-585) | 141 (102-427) | 284 (141-427) | 102 (—) |
| Ongoing, n (%) | 3 (27) | 2 (40) | 1 (17) | 6 (67) | 1 (33) | 5 (83) |
| Duration if ongoing (d), median (range) | 989 (402-1321) | 1155 (989-1321) | 402 (—) | 285.5 (85-1035) | 329 (—) | 242 (85-1035) |
| Any B symptoms reported at the time of onset of IR | ||||||
| Yes, n (%) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| Missing, n (%) | 1 (9) | 1 (20) | — | 0 (0) | — | — |
| LDH levels at the time of onset of IR, n (%) | ||||||
| ≤ULN | 5 (45) | 3 (60) | 2 (33) | 6 (67) | 1 (33) | 5 (83) |
| >ULN | 3 (27) | — | 3 (50) | 3 (33) | 2 (67) | 1 (17) |
| >2 × ULN | — | — | — | — | — | — |
| Missing, n (%) | 3 (27) | 2 (40) | 1 (17) | — | — | — |
| CRP at time of onset of IR, median (range) | 3.3 (1.1-7) | 2.5 (1.7-3.3) | 4.5 (1.1-7) | 1.5 (0.3-53) | 0.9 (0.7-43) | 2 (0.3-53) |
| Missing, n (%) | 6 (55) | 3 (60) | 3 (50) | 1 (11) | — | 1 (17) |
| IR in irradiated field if patient received RT, yes, n (%) | — | — | — | 5 (100) | 2 (100) | 3 (100) |
allo-SCT, allogeneic stem cell transplantation; auto-SCT, autologous stem cell transplantation; CMR, complete metabolic response; CRP, C-reactive protein; DLBCL, diffuse large B-cell lymphoma; LDH, lactate dehydrogenase; PD, progressive disease; PMR, partial metabolic response; RT, radiotherapy; tFL, transformed follicular lymphoma.
Two patients experienced both an HR and an SLR simultaneously; thus, a total 20 IRs were observed in 18 patients.
At screening for CAR-T therapy.