Treatment exposure and dose modifications
| . | 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) . | |
| No. of treatment cycles received, n (%) | |||||||
| 1 | 2 (29) | 3 (25) | 1 (11) | 1 (11) | 1 (13) | 4 (19) | 8 (18) |
| 2 | 2 (29) | 1 (8) | 1 (11) | 2 (22) | 0 (0) | 2 (10) | 6 (13) |
| 3-5 | 0 (0) | 4 (33) | 2 (22) | 4 (44) | 1 (13) | 6 (29) | 11 (24) |
| 6 | 1 (14) | 0 (0) | 1 (11) | 1 (11) | 2 (25) | 1 (5) | 5 (11) |
| 7-12 | 2 (29) | 2 (17) | 1 (11) | 0 (0) | 1 (13) | 3 (14) | 6 (13) |
| >12 | 0 (0) | 2 (17) | 3 (33) | 1 (11) | 3 (38) | 5 (24) | 9 (20) |
| Mean relative dose intensity, % (SD)* | |||||||
| Ibrutinib | 94.6 (6.50) | 89.1 (14.11) | 80.5 (13.44) | 85.3 (18.98) | 78.3 (21.44) | 85.4 (14.17) | 85.6 (16.07) |
| Lenalidomide | 79.6 (34.30) | 81.2 (16.48) | 69.5 (27.02) | 69.6 (27.70) | 64.9 (26.45) | 76.2 (21.83) | 73.4 (25.57) |
| Rituximab | 100 (0.00) | 100 (0.00) | 100 (0.00) | 98.6 (4.17) | 100.1 (0.35) | 100 (0.00) | 99.7 (1.87) |
| Dose delay or reduction because of an AE, n (%) | 4 (57) | 7 (58) | 7 (78) | 8 (89) | 8 (100) | 14 (67) | 34 (76) |
| Dose reduction† | 0 (0) | 4 (33) | 4 (44) | 4 (44) | 5 (63) | 8 (38) | 17 (38) |
| Ibrutinib | 0 (0) | 2 (17) | 4 (44) | 3 (33) | 3 (38) | 6 (29) | 12 (27) |
| Lenalidomide | 0 (0) | 2 (17) | 3 (33) | 4 (44) | 4 (50) | 5 (24) | 13 (29) |
| Rituximab | 0 (0) | 0 (0) | 0 (0) | 1 (11) | 0 (0) | 0 (0) | 1 (2) |
| Dose delay‡ | 4 (57) | 7 (58) | 7 (78) | 8 (89) | 8 (100) | 14 (67) | 34 (76) |
| Ibrutinib | 4 (57) | 6 (50) | 7 (78) | 8 (89) | 8 (100) | 13 (62) | 33 (73) |
| Lenalidomide | 2 (29) | 4 (33) | 4 (44) | 7 (78) | 7 (88) | 8 (38) | 24 (53) |
| Rituximab | 1 (14) | 1 (8) | 1 (11) | 0 (0) | 0 (0) | 2 (10) | 3 (7) |
| . | 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) . | |
| No. of treatment cycles received, n (%) | |||||||
| 1 | 2 (29) | 3 (25) | 1 (11) | 1 (11) | 1 (13) | 4 (19) | 8 (18) |
| 2 | 2 (29) | 1 (8) | 1 (11) | 2 (22) | 0 (0) | 2 (10) | 6 (13) |
| 3-5 | 0 (0) | 4 (33) | 2 (22) | 4 (44) | 1 (13) | 6 (29) | 11 (24) |
| 6 | 1 (14) | 0 (0) | 1 (11) | 1 (11) | 2 (25) | 1 (5) | 5 (11) |
| 7-12 | 2 (29) | 2 (17) | 1 (11) | 0 (0) | 1 (13) | 3 (14) | 6 (13) |
| >12 | 0 (0) | 2 (17) | 3 (33) | 1 (11) | 3 (38) | 5 (24) | 9 (20) |
| Mean relative dose intensity, % (SD)* | |||||||
| Ibrutinib | 94.6 (6.50) | 89.1 (14.11) | 80.5 (13.44) | 85.3 (18.98) | 78.3 (21.44) | 85.4 (14.17) | 85.6 (16.07) |
| Lenalidomide | 79.6 (34.30) | 81.2 (16.48) | 69.5 (27.02) | 69.6 (27.70) | 64.9 (26.45) | 76.2 (21.83) | 73.4 (25.57) |
| Rituximab | 100 (0.00) | 100 (0.00) | 100 (0.00) | 98.6 (4.17) | 100.1 (0.35) | 100 (0.00) | 99.7 (1.87) |
| Dose delay or reduction because of an AE, n (%) | 4 (57) | 7 (58) | 7 (78) | 8 (89) | 8 (100) | 14 (67) | 34 (76) |
| Dose reduction† | 0 (0) | 4 (33) | 4 (44) | 4 (44) | 5 (63) | 8 (38) | 17 (38) |
| Ibrutinib | 0 (0) | 2 (17) | 4 (44) | 3 (33) | 3 (38) | 6 (29) | 12 (27) |
| Lenalidomide | 0 (0) | 2 (17) | 3 (33) | 4 (44) | 4 (50) | 5 (24) | 13 (29) |
| Rituximab | 0 (0) | 0 (0) | 0 (0) | 1 (11) | 0 (0) | 0 (0) | 1 (2) |
| Dose delay‡ | 4 (57) | 7 (58) | 7 (78) | 8 (89) | 8 (100) | 14 (67) | 34 (76) |
| Ibrutinib | 4 (57) | 6 (50) | 7 (78) | 8 (89) | 8 (100) | 13 (62) | 33 (73) |
| Lenalidomide | 2 (29) | 4 (33) | 4 (44) | 7 (78) | 7 (88) | 8 (38) | 24 (53) |
| Rituximab | 1 (14) | 1 (8) | 1 (11) | 0 (0) | 0 (0) | 2 (10) | 3 (7) |
Calculated as the total received dose level divided by the total expected dose level up to the last treatment.
Ibrutinib dose reduced to 420 mg in 11 (24%) patients and 280 mg in 4 (9%) patients; lenalidomide dose reduced to 20 mg in 3 (7%) patients, 15 mg in 6 (13%) patients, 10 mg in 11 (24%) patients, and 5 mg in 5 (11%) patients; rituximab dose reduced to 450 mg in 1 (2%) patient.
Delays of ≥7 d reported for ibrutinib in 23 (51%) patients and for lenalidomide in 15 (33%) patients.