Characteristics of patients with multiple myeloma treated with BCMA-directed CAR T cells
| Neurotoxicity after BCMA-directed CAR T-cell therapy . | No ICANS (%) . | ICANS grade 1-4 (%) . | Total (%) . | P value . |
|---|---|---|---|---|
| Overall, n (%) | n = 45 | n = 31 | n = 76 | |
| Demographics | ||||
| Age at CAR T-cell transfusion (y) | 63.5 ± 1.3 | 65.5 ± 1.6 | 64.3 ± 1.0 | .346 |
| M:F ratio | 1:0.6 | 1:0.6 | 1:0.6 | .839 |
| Clinical characteristics | ||||
| ECOG at CAR T-cell transfusion (median, range) | 1 (0-3) | 1 (0-2) | 1 (0-3) | .566 |
| Presence of neurologic symptoms | 2 (4.4) | 5 (16.1) | 7 (9.2) | .083 |
| Disease entity | ||||
| IgG | 24 (53.3) | 14 (45.2) | 38 (50.0) | .613 |
| IgA | 8 (17.8) | 9 (29.0) | 17 (22.4) | |
| IgD | 1 (2.2) | 0 | 1 (1.3) | |
| Light chain | 11 (24.4) | 8 (25.8) | 19 (25.0) | |
| Nonsecretory | 1 (2.2) | 0 | 1 (1.3) | |
| Previous therapies | ||||
| Median therapy lines (median, range) | 5.0 (1-11) | 6.0 (1-10) | 5.0 (1-11) | .101 |
| Lenalidomide | 45 (100) | 29 (93.6) | 74 (97.4) | .994 |
| Bortezomib | 42 (93.3) | 30 (96.8) | 72 (94.7) | |
| Pomalidomide | 38 (84.4) | 27 (87.1) | 65 (85.5) | |
| Carfilzomib | 31 (68.9) | 22 (71.0) | 43 (56.6) | |
| Daratumumab | 24 (53.3) | 15 (48.4) | 39 (51.3) | |
| ASCT | 25 (55.6) | 20 (64.4) | 45 (59.2) | |
| Bridging | ||||
| Cyclophosphamide | 12 (26.7) | 8 (25.8) | 20 (26.3) | .377 |
| Bortezomib | 11 (24.4) | 5 (16.1) | 16 (21.1) | |
| Pomalidomide | 5 (11.1) | 8 (25.8) | 13 (17.1) | |
| Carfilzomib | 5 (11.1) | 7 (22.6) | 12 (15.8) | |
| None | 15 (33.3) | 9 (29.0) | 31 (40.8) | |
| Lymphodepletion | ||||
| Fludarabine/cyclophosphamide | 44 (97.8) | 31 (100) | 75 (98.7) | .403 |
| Cyclophosphamide alone | 1 (2.2) | 0 | 1 (1.3) | |
| Baseline laboratory findings | ||||
| CRP (mg/L) | 26.9 ± 6.5 | 34.6 ± 10.1 | 30.1 ± 5.6 | .275 |
| Ferritin (μg/L) | 1058 ± 264 | 1255 ± 345 | 1139 ± 210 | .481 |
| Platelets (103/μL) | 112 ± 9.3 | 100 ± 10.4 | 107 ± 7.0 | .396 |
| Albumin (g/dL) | 3.4 ± 0.1 | 3.1 ± 0.1 | 3.3 ± 0.1 | .024 |
| LDH (U/L) | 245 ± 24 | 337 ± 143 | 283 ± 60 | .387 |
| CAR T-cell product | ||||
| Idecabtagene vicleucel | 22 (48.9) | 14 (45.2) | 36 (47.4) | .405 |
| Ciltacabtagene autoleucel | 2 (4.4) | 4 (12.9) | 6 (7.9) | |
| Others∗ | 21 (46.7) | 13 (41.9) | 34 (44.7) | |
| Vein-to-vein time (d) | 39.8 ± 1.5 | 39.4 ± 1.5 | 39.6 ± 1.1 | .545 |
| CD3+ cells per lymphocytes in peripheral blood (on day 7-31; %) | 84.3 ± 3.7 | 80.6 ± 4.9 | 82.8 ± 2.9 | .540 |
| CRS | ||||
| None | 6 (13.3) | 1 (3.2) | 7 (9.2) | .041 |
| Grade 1-2 | 39 (86.7) | 27 (87.1) | 66 (86.8) | |
| Grade 3-4 | 0 | 3 (9.7) | 3 (4.0) | |
| Anti-inflammatory therapy | ||||
| Tocilizumab | 22 (48.9) | 19 (61.3) | 41 (91.1) | .286 |
| Anakinra | 1 (2.2) | 9 (29.0) | 10 (13.2) | .001 |
| Dexamethasone | 10 (34.5) | 19 (65.2) | 29 (38.2) | .001 |
| Neurotoxicity after BCMA-directed CAR T-cell therapy . | No ICANS (%) . | ICANS grade 1-4 (%) . | Total (%) . | P value . |
|---|---|---|---|---|
| Overall, n (%) | n = 45 | n = 31 | n = 76 | |
| Demographics | ||||
| Age at CAR T-cell transfusion (y) | 63.5 ± 1.3 | 65.5 ± 1.6 | 64.3 ± 1.0 | .346 |
| M:F ratio | 1:0.6 | 1:0.6 | 1:0.6 | .839 |
| Clinical characteristics | ||||
| ECOG at CAR T-cell transfusion (median, range) | 1 (0-3) | 1 (0-2) | 1 (0-3) | .566 |
| Presence of neurologic symptoms | 2 (4.4) | 5 (16.1) | 7 (9.2) | .083 |
| Disease entity | ||||
| IgG | 24 (53.3) | 14 (45.2) | 38 (50.0) | .613 |
| IgA | 8 (17.8) | 9 (29.0) | 17 (22.4) | |
| IgD | 1 (2.2) | 0 | 1 (1.3) | |
| Light chain | 11 (24.4) | 8 (25.8) | 19 (25.0) | |
| Nonsecretory | 1 (2.2) | 0 | 1 (1.3) | |
| Previous therapies | ||||
| Median therapy lines (median, range) | 5.0 (1-11) | 6.0 (1-10) | 5.0 (1-11) | .101 |
| Lenalidomide | 45 (100) | 29 (93.6) | 74 (97.4) | .994 |
| Bortezomib | 42 (93.3) | 30 (96.8) | 72 (94.7) | |
| Pomalidomide | 38 (84.4) | 27 (87.1) | 65 (85.5) | |
| Carfilzomib | 31 (68.9) | 22 (71.0) | 43 (56.6) | |
| Daratumumab | 24 (53.3) | 15 (48.4) | 39 (51.3) | |
| ASCT | 25 (55.6) | 20 (64.4) | 45 (59.2) | |
| Bridging | ||||
| Cyclophosphamide | 12 (26.7) | 8 (25.8) | 20 (26.3) | .377 |
| Bortezomib | 11 (24.4) | 5 (16.1) | 16 (21.1) | |
| Pomalidomide | 5 (11.1) | 8 (25.8) | 13 (17.1) | |
| Carfilzomib | 5 (11.1) | 7 (22.6) | 12 (15.8) | |
| None | 15 (33.3) | 9 (29.0) | 31 (40.8) | |
| Lymphodepletion | ||||
| Fludarabine/cyclophosphamide | 44 (97.8) | 31 (100) | 75 (98.7) | .403 |
| Cyclophosphamide alone | 1 (2.2) | 0 | 1 (1.3) | |
| Baseline laboratory findings | ||||
| CRP (mg/L) | 26.9 ± 6.5 | 34.6 ± 10.1 | 30.1 ± 5.6 | .275 |
| Ferritin (μg/L) | 1058 ± 264 | 1255 ± 345 | 1139 ± 210 | .481 |
| Platelets (103/μL) | 112 ± 9.3 | 100 ± 10.4 | 107 ± 7.0 | .396 |
| Albumin (g/dL) | 3.4 ± 0.1 | 3.1 ± 0.1 | 3.3 ± 0.1 | .024 |
| LDH (U/L) | 245 ± 24 | 337 ± 143 | 283 ± 60 | .387 |
| CAR T-cell product | ||||
| Idecabtagene vicleucel | 22 (48.9) | 14 (45.2) | 36 (47.4) | .405 |
| Ciltacabtagene autoleucel | 2 (4.4) | 4 (12.9) | 6 (7.9) | |
| Others∗ | 21 (46.7) | 13 (41.9) | 34 (44.7) | |
| Vein-to-vein time (d) | 39.8 ± 1.5 | 39.4 ± 1.5 | 39.6 ± 1.1 | .545 |
| CD3+ cells per lymphocytes in peripheral blood (on day 7-31; %) | 84.3 ± 3.7 | 80.6 ± 4.9 | 82.8 ± 2.9 | .540 |
| CRS | ||||
| None | 6 (13.3) | 1 (3.2) | 7 (9.2) | .041 |
| Grade 1-2 | 39 (86.7) | 27 (87.1) | 66 (86.8) | |
| Grade 3-4 | 0 | 3 (9.7) | 3 (4.0) | |
| Anti-inflammatory therapy | ||||
| Tocilizumab | 22 (48.9) | 19 (61.3) | 41 (91.1) | .286 |
| Anakinra | 1 (2.2) | 9 (29.0) | 10 (13.2) | .001 |
| Dexamethasone | 10 (34.5) | 19 (65.2) | 29 (38.2) | .001 |
Characteristics are given for patients without neurotoxicity (n = 45), neurotoxicity (n = 31), and summarized for all cases (total; N = 76). Differences between the groups were analyzed using the unpaired Student t test (for parametric data) or the Mann-Whitney U test (for nonparametric data) for continuous variables; and categorical variables were assessed by the χ2-test. No correction for multiple testing was done. P values are given, and boldface indicates P ≤ .05.
ASCT, autologous stem cell transplantation; CRP, C-reactive protein; ECOG, Eastern Cooperative Oncology Group performance status; F, female; Ig, immunoglobulin; LDH, lactate dehydrogenase; M, male.
Others: mainly CART-ddBCMA (NCT04155749), bb21217 (NCT03274219), and TriPRIL CAR T cells (NCT05020444).