Summary of TEAEs
| . | 560 mg/day ibrutinib + 375 mg/m2 IV rituximab combined with: . | ||||||
|---|---|---|---|---|---|---|---|
| Dose level −1: 10 mg LEN (n = 7) . | Dose level 1: 15 mg LEN (n = 12) . | Dose level 1+:15 mg LEN (n = 9) . | Dose level 2:20 mg LEN (n = 9) . | Dose level 3:25 mg LEN (n = 8) . | Dose level 1 combined (n = 21) . | All dose levels (N = 45) . | |
| TEAEs in ≥20% of patients, n (%) | |||||||
| Diarrhea | 3 (43) | 9 (75) | 2 (22) | 4 (44) | 6 (75) | 11 (52) | 24 (53) |
| Nausea | 3 (43) | 7 (58) | 4 (44) | 3 (33) | 5 (63) | 11 (52) | 22 (49) |
| Fatigue | 3 (43) | 6 (50) | 5 (56) | 2 (22) | 4 (50) | 11 (52) | 20 (44) |
| Neutropenia | 0 (0) | 5 (42) | 6 (67) | 3 (33) | 4 (50) | 11 (52) | 18 (40) |
| Constipation | 2 (29) | 5 (42) | 4 (44) | 4 (44) | 2 (25) | 9 (43) | 17 (38) |
| Thrombocytopenia | 2 (29) | 4 (33) | 3 (33) | 4 (44) | 3 (38) | 7 (33) | 16 (36) |
| Hypokalemia | 1 (14) | 4 (33) | 3 (33) | 3 (33) | 3 (38) | 7 (33) | 14 (31) |
| Anemia | 0 (0) | 3 (25) | 5 (56) | 3 (33) | 2 (25) | 8 (38) | 13 (29) |
| Peripheral edema | 1 (14) | 2 (17) | 3 (33) | 3 (33) | 4 (50) | 5 (24) | 13 (29) |
| Maculopapular rash | 1 (14) | 2 (17) | 5 (56) | 3 (33) | 2 (25) | 7 (33) | 13 (29) |
| Vomiting | 1 (14) | 3 (25) | 2 (22) | 3 (33) | 3 (38) | 5 (24) | 12 (27) |
| Decreased appetite | 1 (14) | 2 (17) | 4 (44) | 2 (22) | 2 (25) | 6 (29) | 11 (24) |
| Dizziness | 0 (0) | 4 (33) | 2 (22) | 3 (33) | 2 (25) | 6 (29) | 11 (24) |
| Dyspnea | 1 (14) | 3 (25) | 1 (11) | 3 (33) | 2 (25) | 4 (19) | 10 (22) |
| Abdominal pain | 2 (29) | 2 (17) | 0 (0) | 3 (33) | 2 (25) | 2 (10) | 9 (20) |
| Decreased weight | 2 (29) | 3 (25) | 0 (0) | 1 (11) | 3 (38) | 3 (14) | 9 (20) |
| Any grade 3-4 TEAE, n (%) | 5 (71) | 11 (92) | 8 (89) | 9 (100) | 7 (88) | 19 (90) | 40 (89) |
| Ibrutinib related | 3 (43) | 10 (83) | 6 (67) | 7 (78) | 6 (75) | 16 (76) | 32 (71) |
| Lenalidomide related | 3 (43) | 9 (75) | 7 (78) | 7 (78) | 5 (63) | 16 (76) | 31 (69) |
| Any serious TEAE, n (%) | 5 (71) | 3 (25) | 7 (78) | 5 (56) | 5 (63) | 10 (48) | 25 (56) |
| Serious TEAEs in ≥5% of patients, n (%) | |||||||
| Worsening of DLBCL | 1 (14) | 0 (0) | 1 (11) | 2 (22) | 1 (13) | 1 (5) | 5 (11) |
| Febrile neutropenia | 0 (0) | 0 (0) | 0 (0) | 2 (22) | 1 (13) | 0 (0) | 3 (7) |
| Atrial fibrillation | 0 (0) | 0 (0) | 0 (0) | 2 (22) | 1 (13) | 0 (0) | 3 (7) |
| Dehydration | 0 (0) | 0 (0) | 1 (11) | 1 (11) | 1 (13) | 1 (5) | 3 (7) |
| Any grade 5 TEAE, n (%)* | 1 (14) | 0 (0) | 2 (22) | 1 (11) | 1 (13) | 2 (10) | 5 (11) |
| Discontinuation due to TEAE, n (%) | 1 (14) | 4 (33) | 3 (33) | 2 (22) | 1 (13) | 7 (33) | 11 (24) |
| . | 560 mg/day ibrutinib + 375 mg/m2 IV rituximab combined with: . | ||||||
|---|---|---|---|---|---|---|---|
| Dose level −1: 10 mg LEN (n = 7) . | Dose level 1: 15 mg LEN (n = 12) . | Dose level 1+:15 mg LEN (n = 9) . | Dose level 2:20 mg LEN (n = 9) . | Dose level 3:25 mg LEN (n = 8) . | Dose level 1 combined (n = 21) . | All dose levels (N = 45) . | |
| TEAEs in ≥20% of patients, n (%) | |||||||
| Diarrhea | 3 (43) | 9 (75) | 2 (22) | 4 (44) | 6 (75) | 11 (52) | 24 (53) |
| Nausea | 3 (43) | 7 (58) | 4 (44) | 3 (33) | 5 (63) | 11 (52) | 22 (49) |
| Fatigue | 3 (43) | 6 (50) | 5 (56) | 2 (22) | 4 (50) | 11 (52) | 20 (44) |
| Neutropenia | 0 (0) | 5 (42) | 6 (67) | 3 (33) | 4 (50) | 11 (52) | 18 (40) |
| Constipation | 2 (29) | 5 (42) | 4 (44) | 4 (44) | 2 (25) | 9 (43) | 17 (38) |
| Thrombocytopenia | 2 (29) | 4 (33) | 3 (33) | 4 (44) | 3 (38) | 7 (33) | 16 (36) |
| Hypokalemia | 1 (14) | 4 (33) | 3 (33) | 3 (33) | 3 (38) | 7 (33) | 14 (31) |
| Anemia | 0 (0) | 3 (25) | 5 (56) | 3 (33) | 2 (25) | 8 (38) | 13 (29) |
| Peripheral edema | 1 (14) | 2 (17) | 3 (33) | 3 (33) | 4 (50) | 5 (24) | 13 (29) |
| Maculopapular rash | 1 (14) | 2 (17) | 5 (56) | 3 (33) | 2 (25) | 7 (33) | 13 (29) |
| Vomiting | 1 (14) | 3 (25) | 2 (22) | 3 (33) | 3 (38) | 5 (24) | 12 (27) |
| Decreased appetite | 1 (14) | 2 (17) | 4 (44) | 2 (22) | 2 (25) | 6 (29) | 11 (24) |
| Dizziness | 0 (0) | 4 (33) | 2 (22) | 3 (33) | 2 (25) | 6 (29) | 11 (24) |
| Dyspnea | 1 (14) | 3 (25) | 1 (11) | 3 (33) | 2 (25) | 4 (19) | 10 (22) |
| Abdominal pain | 2 (29) | 2 (17) | 0 (0) | 3 (33) | 2 (25) | 2 (10) | 9 (20) |
| Decreased weight | 2 (29) | 3 (25) | 0 (0) | 1 (11) | 3 (38) | 3 (14) | 9 (20) |
| Any grade 3-4 TEAE, n (%) | 5 (71) | 11 (92) | 8 (89) | 9 (100) | 7 (88) | 19 (90) | 40 (89) |
| Ibrutinib related | 3 (43) | 10 (83) | 6 (67) | 7 (78) | 6 (75) | 16 (76) | 32 (71) |
| Lenalidomide related | 3 (43) | 9 (75) | 7 (78) | 7 (78) | 5 (63) | 16 (76) | 31 (69) |
| Any serious TEAE, n (%) | 5 (71) | 3 (25) | 7 (78) | 5 (56) | 5 (63) | 10 (48) | 25 (56) |
| Serious TEAEs in ≥5% of patients, n (%) | |||||||
| Worsening of DLBCL | 1 (14) | 0 (0) | 1 (11) | 2 (22) | 1 (13) | 1 (5) | 5 (11) |
| Febrile neutropenia | 0 (0) | 0 (0) | 0 (0) | 2 (22) | 1 (13) | 0 (0) | 3 (7) |
| Atrial fibrillation | 0 (0) | 0 (0) | 0 (0) | 2 (22) | 1 (13) | 0 (0) | 3 (7) |
| Dehydration | 0 (0) | 0 (0) | 1 (11) | 1 (11) | 1 (13) | 1 (5) | 3 (7) |
| Any grade 5 TEAE, n (%)* | 1 (14) | 0 (0) | 2 (22) | 1 (11) | 1 (13) | 2 (10) | 5 (11) |
| Discontinuation due to TEAE, n (%) | 1 (14) | 4 (33) | 3 (33) | 2 (22) | 1 (13) | 7 (33) | 11 (24) |
Includes study treatment–related Escherichia sepsis in 1 patient in dose cohort 1+ and worsening of DLBCL in 4 patients. One additional death occurred that was not considered a TEAE, as it occurred 16 days after receiving subsequent anticancer therapy in a patient who discontinued ibrutinib. TEAEs were defined as AEs occurring after the first dose of study drugs and within 30 days after the last dose of study drug; any AE that is considered study drug-related regardless of the start date of the event; or any AE that is present at baseline but worsens after the first administration of study drug in severity or is subsequently considered drug-related by the investigator.