Adverse event summary in the overall population and by subgroup
| Event . | Overall N = 476 . | BTKi . | Prior therapies . | Bendamustine . | |||
|---|---|---|---|---|---|---|---|
| Prior, n = 412 . | No prior, n = 57 . | 1-2 lines, n = 104 . | ≥3 lines, n = 365 . | Prior, n = 259 . | No prior, n = 210 . | ||
| CRS∗,† | |||||||
| Any grade, % (95% CI) | 89 (86-92) | 89 (85-92) | 91 (81-97) | 92 (85-97) | 88 (84-91) | 88 (83-91) | 91 (86-94) |
| Grade ≥3, % (95% CI)‡ | 11 (8-14) | 11 (8-15) | 9 (3-19) | 13 (8-22) | 10 (7-14) | 9 (6-13) | 13 (9-19) |
| Grade 4, n/n (%) | 16/473 (3) | 14/409 (3) | 2/57 (4) | 4/104 (4) | 12/362 (3) | 8/258 (3) | 8/208 (4) |
| Grade 5, n/n (%) | 9/473 (2)§ | 8/409 (2) | 1/57 (2) | 1/104 (<1) | 8/362 (2) | 4/258 (2) | 5/208 (2) |
| Time to onset, median (range), d | 5.0 (1.0-46.0) | 5.0 (1.0-46.0) | 5.0 (1.0-11.0) | 5.0 (1.0-13.0) | 5.0 (1.0-46.0) | 5.0 (1.0-46.0) | 5.0 (1.0-13.0) |
| Duration, median (range), d | 6.0 (1.0-176.0) | 6.0 (1.0-80.0) | 6.0 (1.0-176.0) | 6.0 (1.0-41.0) | 6.0 (1.0-176.0) | 5.0 (1.0-80.0) | 6.0 (1.0-176.0) |
| Cumulative incidence of resolution estimate at week 3 after onset, % (95% CI)|| | 95 (92-96) | 95 (92-96) | 94 (82-98) | 96 (89-99) | 94 (91-96) | 93 (89-96) | 96 (92-98) |
| ICANS∗,† | |||||||
| Any grade, % (95% CI) | 62 (57-66) | 61 (56-66) | 67 (53-79) | 63 (53-73) | 61 (56-66) | 59 (53-65) | 65 (58-71) |
| Grade ≥3, % (95% CI)‡ | 30 (26-34) | 30 (26-35) | 31 (19-45) | 31 (22-41) | 30 (25-35) | 25 (19-30) | 37 (30-44) |
| Grade 4, n/n (%) | 32/459 (7) | 26/397 (7) | 6/55 (11) | 8/103 (8) | 24/349 (7) | 12/248 (5) | 20/204 (10) |
| Grade 5, n/n (%) | 9/459 (2)¶ | 8/397 (2) | 1/55 (2) | 3/103 (3) | 6/349 (2) | 6/248 (2) | 3/204 (1) |
| Time to onset, median (range), d | 7.0 (1.0-31.0) | 7.0 (1.0-31.0) | 9.0 (1.0-16.0) | 8.0 (2.0-20.0) | 7.0 (1.0-31.0) | 7.0 (1.0-29.0) | 7.0 (1.0-31.0) |
| Duration, median (range), d | 8.0 (1.0-98.0) | 8.0 (1.0-98.0) | 5.0 (2.0-49.0) | 8.0 (1.0-66.0) | 8.5 (1.0-98.0) | 7.0 (1.0-70.0) | 9.0 (1.0-98.0) |
| Cumulative incidence of resolution estimate at week 3 after onset, % (95% CI)|| | 76 (71-81) | 76 (70-81) | 78 (61-89) | 83 (71-90) | 74 (68-79) | 77 (69-83) | 75 (67-82) |
| Treatment for CRS and/or ICANS, n/n (%) | |||||||
| Tocilizumab | 361/475 (76) | 310/411 (75) | 46/57 (81) | 82/104 (79) | 274/364 (75) | 192/259 (74) | 164/209 (78) |
| Corticosteroids | 292/475 (61) | 252/411 (61) | 37/57 (65) | 68/104 (65) | 221/364 (61) | 150/259 (58) | 139/209 (67) |
| Anakinra | 75/475 (16) | 66/411 (16) | 9/57 (16) | 20/104 (19) | 55/364 (15) | 30/259 (12) | 45/209 (22) |
| Siltuximab | 22/475 (5) | 19/411 (5) | 3/57 (5) | 11/104 (11) | 11/364 (3) | 8/259 (3) | 14/209 (7) |
| Prolonged cytopenia, % (95% CI)‡,# | 25 (21-30) | 26 (22-31) | 20 (11-34) | 21 (14-31) | 27 (22-32) | 31 (25-37) | 19 (14-25) |
| Neutropenia | 14 (11-18) | 15 (12-19) | 7 (2-18) | 12 (6-20) | 15 (12-19) | 18 (13-23) | 10 (6-15) |
| Thrombocytopenia | 19 (16-23) | 19 (16-24) | 19 (9-31) | 14 (8-23) | 21 (17-25) | 23 (18-29) | 15 (10-21) |
| Cumulative incidence of NRM, % (95% CI)∗∗ | |||||||
| Day 100 | 4 (3-6) | 4 (2-6) | 9 (3-19) | 7 (3-13) | 3 (2-6) | 4 (2-7) | 4 (2-8) |
| Day 180 | 6 (4-8) | 5 (3-7) | 11 (4-21) | 9 (4-15) | 5 (3-7) | 6 (4-9) | 5 (3-9) |
| Year 1 | 8 (6-11) | 8 (5-11) | 13 (6-23) | 10 (5-17) | 8 (5-11) | 8 (5-12) | 8 (5-13) |
| Clinically significant infection, n/n (%) | 239/475 (50) | 211/411 (51) | 25/57 (44) | 43/104 (41) | 193/364 (53) | 129/258 (50) | 107/210 (51) |
| Viral | 164/475 (35) | 143/411 (35) | 19/57 (33) | 34/104 (33) | 128/364 (35) | 88/258 (34) | 74/210 (35) |
| Bacterial | 112/475 (24) | 97/411 (24) | 13/57 (23) | 17/104 (16) | 93/364 (26) | 56/258 (22) | 54/210 (26) |
| Fungal | 24/475 (5) | 22/411 (5) | 2/57 (4) | 3/104 (3) | 21/364 (6) | 16/258 (6) | 8/210 (4) |
| Other | 31/475 (7) | 26/411 (6) | 4/57 (7) | 6/104 (6) | 24/364 (7) | 12/258 (5) | 18/210 (9) |
| Not reported, n | 1 | 1 | 0 | 0 | 1 | 1 | 0 |
| Subsequent neoplasms, n (%)†† | 41 (9) | 37 (9) | 4 (7) | 6 (6) | 35 (10) | 27 (10) | 14 (7) |
| Therapy-related myeloid neoplasms at year 1, % (95% CI)‡‡ | 1 (<1-2) | ND | ND | ND | ND | ND | ND |
| Nonmelanoma skin cancer at year 1, % (95% CI)‡‡ | 3 (1-5) | ND | ND | ND | ND | ND | ND |
| Event . | Overall N = 476 . | BTKi . | Prior therapies . | Bendamustine . | |||
|---|---|---|---|---|---|---|---|
| Prior, n = 412 . | No prior, n = 57 . | 1-2 lines, n = 104 . | ≥3 lines, n = 365 . | Prior, n = 259 . | No prior, n = 210 . | ||
| CRS∗,† | |||||||
| Any grade, % (95% CI) | 89 (86-92) | 89 (85-92) | 91 (81-97) | 92 (85-97) | 88 (84-91) | 88 (83-91) | 91 (86-94) |
| Grade ≥3, % (95% CI)‡ | 11 (8-14) | 11 (8-15) | 9 (3-19) | 13 (8-22) | 10 (7-14) | 9 (6-13) | 13 (9-19) |
| Grade 4, n/n (%) | 16/473 (3) | 14/409 (3) | 2/57 (4) | 4/104 (4) | 12/362 (3) | 8/258 (3) | 8/208 (4) |
| Grade 5, n/n (%) | 9/473 (2)§ | 8/409 (2) | 1/57 (2) | 1/104 (<1) | 8/362 (2) | 4/258 (2) | 5/208 (2) |
| Time to onset, median (range), d | 5.0 (1.0-46.0) | 5.0 (1.0-46.0) | 5.0 (1.0-11.0) | 5.0 (1.0-13.0) | 5.0 (1.0-46.0) | 5.0 (1.0-46.0) | 5.0 (1.0-13.0) |
| Duration, median (range), d | 6.0 (1.0-176.0) | 6.0 (1.0-80.0) | 6.0 (1.0-176.0) | 6.0 (1.0-41.0) | 6.0 (1.0-176.0) | 5.0 (1.0-80.0) | 6.0 (1.0-176.0) |
| Cumulative incidence of resolution estimate at week 3 after onset, % (95% CI)|| | 95 (92-96) | 95 (92-96) | 94 (82-98) | 96 (89-99) | 94 (91-96) | 93 (89-96) | 96 (92-98) |
| ICANS∗,† | |||||||
| Any grade, % (95% CI) | 62 (57-66) | 61 (56-66) | 67 (53-79) | 63 (53-73) | 61 (56-66) | 59 (53-65) | 65 (58-71) |
| Grade ≥3, % (95% CI)‡ | 30 (26-34) | 30 (26-35) | 31 (19-45) | 31 (22-41) | 30 (25-35) | 25 (19-30) | 37 (30-44) |
| Grade 4, n/n (%) | 32/459 (7) | 26/397 (7) | 6/55 (11) | 8/103 (8) | 24/349 (7) | 12/248 (5) | 20/204 (10) |
| Grade 5, n/n (%) | 9/459 (2)¶ | 8/397 (2) | 1/55 (2) | 3/103 (3) | 6/349 (2) | 6/248 (2) | 3/204 (1) |
| Time to onset, median (range), d | 7.0 (1.0-31.0) | 7.0 (1.0-31.0) | 9.0 (1.0-16.0) | 8.0 (2.0-20.0) | 7.0 (1.0-31.0) | 7.0 (1.0-29.0) | 7.0 (1.0-31.0) |
| Duration, median (range), d | 8.0 (1.0-98.0) | 8.0 (1.0-98.0) | 5.0 (2.0-49.0) | 8.0 (1.0-66.0) | 8.5 (1.0-98.0) | 7.0 (1.0-70.0) | 9.0 (1.0-98.0) |
| Cumulative incidence of resolution estimate at week 3 after onset, % (95% CI)|| | 76 (71-81) | 76 (70-81) | 78 (61-89) | 83 (71-90) | 74 (68-79) | 77 (69-83) | 75 (67-82) |
| Treatment for CRS and/or ICANS, n/n (%) | |||||||
| Tocilizumab | 361/475 (76) | 310/411 (75) | 46/57 (81) | 82/104 (79) | 274/364 (75) | 192/259 (74) | 164/209 (78) |
| Corticosteroids | 292/475 (61) | 252/411 (61) | 37/57 (65) | 68/104 (65) | 221/364 (61) | 150/259 (58) | 139/209 (67) |
| Anakinra | 75/475 (16) | 66/411 (16) | 9/57 (16) | 20/104 (19) | 55/364 (15) | 30/259 (12) | 45/209 (22) |
| Siltuximab | 22/475 (5) | 19/411 (5) | 3/57 (5) | 11/104 (11) | 11/364 (3) | 8/259 (3) | 14/209 (7) |
| Prolonged cytopenia, % (95% CI)‡,# | 25 (21-30) | 26 (22-31) | 20 (11-34) | 21 (14-31) | 27 (22-32) | 31 (25-37) | 19 (14-25) |
| Neutropenia | 14 (11-18) | 15 (12-19) | 7 (2-18) | 12 (6-20) | 15 (12-19) | 18 (13-23) | 10 (6-15) |
| Thrombocytopenia | 19 (16-23) | 19 (16-24) | 19 (9-31) | 14 (8-23) | 21 (17-25) | 23 (18-29) | 15 (10-21) |
| Cumulative incidence of NRM, % (95% CI)∗∗ | |||||||
| Day 100 | 4 (3-6) | 4 (2-6) | 9 (3-19) | 7 (3-13) | 3 (2-6) | 4 (2-7) | 4 (2-8) |
| Day 180 | 6 (4-8) | 5 (3-7) | 11 (4-21) | 9 (4-15) | 5 (3-7) | 6 (4-9) | 5 (3-9) |
| Year 1 | 8 (6-11) | 8 (5-11) | 13 (6-23) | 10 (5-17) | 8 (5-11) | 8 (5-12) | 8 (5-13) |
| Clinically significant infection, n/n (%) | 239/475 (50) | 211/411 (51) | 25/57 (44) | 43/104 (41) | 193/364 (53) | 129/258 (50) | 107/210 (51) |
| Viral | 164/475 (35) | 143/411 (35) | 19/57 (33) | 34/104 (33) | 128/364 (35) | 88/258 (34) | 74/210 (35) |
| Bacterial | 112/475 (24) | 97/411 (24) | 13/57 (23) | 17/104 (16) | 93/364 (26) | 56/258 (22) | 54/210 (26) |
| Fungal | 24/475 (5) | 22/411 (5) | 2/57 (4) | 3/104 (3) | 21/364 (6) | 16/258 (6) | 8/210 (4) |
| Other | 31/475 (7) | 26/411 (6) | 4/57 (7) | 6/104 (6) | 24/364 (7) | 12/258 (5) | 18/210 (9) |
| Not reported, n | 1 | 1 | 0 | 0 | 1 | 1 | 0 |
| Subsequent neoplasms, n (%)†† | 41 (9) | 37 (9) | 4 (7) | 6 (6) | 35 (10) | 27 (10) | 14 (7) |
| Therapy-related myeloid neoplasms at year 1, % (95% CI)‡‡ | 1 (<1-2) | ND | ND | ND | ND | ND | ND |
| Nonmelanoma skin cancer at year 1, % (95% CI)‡‡ | 3 (1-5) | ND | ND | ND | ND | ND | ND |
ASTCT, American Society for Transplantation and Cellular Therapy; ND, not determined.
Based on ASTCT consensus criteria.
With 100-day follow-up.
Among all patients; percentages are based on patients with available data.
Three patients died due to CRS as primary cause of death; 6 patients died with CRS as a contributing cause of death.
Among patients with documented CRS or ICANS during 100-day follow-up; censored at subsequent infusion.
Of 7 patients with neurotoxicity reported as primary cause of death, 1 patient experienced toxic encephalopathy unrelated to ICANS; 3 patients died with ICANS as a contributing cause of death.
Among patients who survived 30 days after infusion.
Relapse/PD was treated as a competing risk.
Includes acute myeloid leukemia; basal cell and squamous cell skin malignancy; gastrointestinal and genitourinary malignancy; breast, lung, and oropharyngeal cancer; melanoma; sarcoma; and myelodysplasia.
Death was treated as a competing risk.