Baseline demographic and clinical characteristics
| . | 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) . | |
| Age | |||||||
| Median age, y (range) | 59 (49-68) | 62 (43-84) | 68 (41-85) | 64 (50-77) | 68 (36-78) | 64 (41-85) | 64 (36-85) |
| ≥65 y, n (%) | 2 (29) | 5 (42) | 5 (56) | 4 (44) | 5 (63) | 10 (48) | 21 (47) |
| Male sex, n (%) | 4 (57) | 8 (67) | 4 (44) | 4 (44) | 5 (63) | 12 (57) | 25 (56) |
| White race, n (%)* | 5 (71) | 11 (92) | 8 (89) | 9 (100) | 7 (88) | 19 (90) | 40 (89) |
| Mean BMI, kg/m2 (SD) | 29.0 (5.80) | 31.0 (10.30) | 29.3 (5.10) | 28.0 (5.50) | 25.9 (4.49) | 30.3 (8.33) | 28.8 (6.90) |
| ECOG PS, n (%) | |||||||
| 0 | 1 (14) | 7 (58) | 2 (22) | 3 (33) | 1 (13) | 9 (43) | 14 (31) |
| 1 | 6 (86) | 5 (42) | 7 (78) | 6 (67) | 7 (88) | 12 (57) | 31 (69) |
| Median time from initial diagnosis, mo (range) | 14.4 (6-38) | 15.2 (8-83) | 11.2 (3-252) | 11.8 (9-72) | 16.9 (7-154) | 14.1 (3-252) | 14.1 (3-252) |
| DLBCL subtype, n (%)† | |||||||
| Non-GCB | 2 (29) | 5 (42) | 8 (89) | 5 (56) | 3 (37) | 13 (61) | 23 (51) |
| GCB | 3 (42) | 5 (42) | 1 (11) | 3 (33) | 5 (63) | 6 (29) | 17 (38) |
| Not reported/missing | 2 (29) | 2 (16) | 0 (0) | 1 (11) | 0 (0) | 2 (10) | 5 (11) |
| DLBCL category, n (%) | |||||||
| De novo | 5 (71) | 8 (67) | 7 (78) | 6 (67) | 4 (50) | 15 (71) | 30 (67) |
| Transformed | 2 (29) | 4 (33) | 2 (22) | 3 (33) | 4 (50) | 6 (29) | 15 (33) |
| Ann Arbor staging, n (%) | |||||||
| II/IIE | 3 (42) | 1 (8) | 1 (11) | 1 (11) | 0 (0) | 2 (9) | 6 (13) |
| III/IIIE/IIIE,S | 2 (29) | 1 (8) | 0 (0) | 2 (22) | 3 (37) | 1 (5) | 8 (18) |
| IV | 2 (29) | 10 (84) | 8 (89) | 6 (67) | 5 (63) | 18 (86) | 31 (69) |
| Bulky disease, n (%) | 6 (86) | 5 (42) | 3 (33) | 5 (56) | 5 (63) | 8 (38) | 24 (53) |
| 5-10 cm | 4 (57) | 2 (17) | 2 (22) | 3 (33) | 5 (63) | 4 (19) | 16 (36) |
| >10 cm | 2 (29) | 3 (25) | 1 (11) | 2 (22) | 0 (0) | 4 (19) | 8 (18) |
| No. of prior regimens, n (%) | |||||||
| 1 | 0 (0) | 2 (17) | 2 (22) | 2 (22) | 1 (13) | 4 (19) | 7 (16) |
| ≥2 | 7 (100) | 10 (83) | 7 (78) | 7 (78) | 7 (88) | 17 (81) | 38 (84) |
| Disease status at completion of treatment regimen preceding study entry, n (%) | |||||||
| Refractory‡ | 4 (57) | 8 (67) | 5 (56) | 5 (56) | 5 (63) | 13 (62) | 27 (60) |
| Relapsed | 3 (43) | 4 (33) | 4 (44) | 4 (44) | 3 (38) | 8 (38) | 18 (40) |
| CR | 1 (14) | 3 (25) | 4 (44) | 4 (44) | 3 (38) | 7 (33) | 15 (33) |
| PR | 2 (29) | 1 (8) | 0 (0) | 0 (0) | 0 (0) | 1 (5) | 3 (7) |
| Primary refractory disease, n (%)¶ | 5 (71) | 3 (25) | 2 (22) | 1 (11) | 1 (13) | 5 (24) | 12 (27) |
| Prior autologous transplant§ | 2 (29) | 3 (25) | 4 (44) | 0 (0) | 2 (25) | 7 (33) | 11 (24) |
| Median time from last dose of prior therapy to first ibrutinib dose, mo (range) | 1.9 (1.1-20.7) | 2.2 (0.7-20.6) | 2.4 (0.7-36.6) | 2.5 (2.1-68.3) | 2.7 (0.0-65.7) | 2.4 (0.7-36.6) | 2.4 (0.0-68.3) |
| . | 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) . | |
| Age | |||||||
| Median age, y (range) | 59 (49-68) | 62 (43-84) | 68 (41-85) | 64 (50-77) | 68 (36-78) | 64 (41-85) | 64 (36-85) |
| ≥65 y, n (%) | 2 (29) | 5 (42) | 5 (56) | 4 (44) | 5 (63) | 10 (48) | 21 (47) |
| Male sex, n (%) | 4 (57) | 8 (67) | 4 (44) | 4 (44) | 5 (63) | 12 (57) | 25 (56) |
| White race, n (%)* | 5 (71) | 11 (92) | 8 (89) | 9 (100) | 7 (88) | 19 (90) | 40 (89) |
| Mean BMI, kg/m2 (SD) | 29.0 (5.80) | 31.0 (10.30) | 29.3 (5.10) | 28.0 (5.50) | 25.9 (4.49) | 30.3 (8.33) | 28.8 (6.90) |
| ECOG PS, n (%) | |||||||
| 0 | 1 (14) | 7 (58) | 2 (22) | 3 (33) | 1 (13) | 9 (43) | 14 (31) |
| 1 | 6 (86) | 5 (42) | 7 (78) | 6 (67) | 7 (88) | 12 (57) | 31 (69) |
| Median time from initial diagnosis, mo (range) | 14.4 (6-38) | 15.2 (8-83) | 11.2 (3-252) | 11.8 (9-72) | 16.9 (7-154) | 14.1 (3-252) | 14.1 (3-252) |
| DLBCL subtype, n (%)† | |||||||
| Non-GCB | 2 (29) | 5 (42) | 8 (89) | 5 (56) | 3 (37) | 13 (61) | 23 (51) |
| GCB | 3 (42) | 5 (42) | 1 (11) | 3 (33) | 5 (63) | 6 (29) | 17 (38) |
| Not reported/missing | 2 (29) | 2 (16) | 0 (0) | 1 (11) | 0 (0) | 2 (10) | 5 (11) |
| DLBCL category, n (%) | |||||||
| De novo | 5 (71) | 8 (67) | 7 (78) | 6 (67) | 4 (50) | 15 (71) | 30 (67) |
| Transformed | 2 (29) | 4 (33) | 2 (22) | 3 (33) | 4 (50) | 6 (29) | 15 (33) |
| Ann Arbor staging, n (%) | |||||||
| II/IIE | 3 (42) | 1 (8) | 1 (11) | 1 (11) | 0 (0) | 2 (9) | 6 (13) |
| III/IIIE/IIIE,S | 2 (29) | 1 (8) | 0 (0) | 2 (22) | 3 (37) | 1 (5) | 8 (18) |
| IV | 2 (29) | 10 (84) | 8 (89) | 6 (67) | 5 (63) | 18 (86) | 31 (69) |
| Bulky disease, n (%) | 6 (86) | 5 (42) | 3 (33) | 5 (56) | 5 (63) | 8 (38) | 24 (53) |
| 5-10 cm | 4 (57) | 2 (17) | 2 (22) | 3 (33) | 5 (63) | 4 (19) | 16 (36) |
| >10 cm | 2 (29) | 3 (25) | 1 (11) | 2 (22) | 0 (0) | 4 (19) | 8 (18) |
| No. of prior regimens, n (%) | |||||||
| 1 | 0 (0) | 2 (17) | 2 (22) | 2 (22) | 1 (13) | 4 (19) | 7 (16) |
| ≥2 | 7 (100) | 10 (83) | 7 (78) | 7 (78) | 7 (88) | 17 (81) | 38 (84) |
| Disease status at completion of treatment regimen preceding study entry, n (%) | |||||||
| Refractory‡ | 4 (57) | 8 (67) | 5 (56) | 5 (56) | 5 (63) | 13 (62) | 27 (60) |
| Relapsed | 3 (43) | 4 (33) | 4 (44) | 4 (44) | 3 (38) | 8 (38) | 18 (40) |
| CR | 1 (14) | 3 (25) | 4 (44) | 4 (44) | 3 (38) | 7 (33) | 15 (33) |
| PR | 2 (29) | 1 (8) | 0 (0) | 0 (0) | 0 (0) | 1 (5) | 3 (7) |
| Primary refractory disease, n (%)¶ | 5 (71) | 3 (25) | 2 (22) | 1 (11) | 1 (13) | 5 (24) | 12 (27) |
| Prior autologous transplant§ | 2 (29) | 3 (25) | 4 (44) | 0 (0) | 2 (25) | 7 (33) | 11 (24) |
| Median time from last dose of prior therapy to first ibrutinib dose, mo (range) | 1.9 (1.1-20.7) | 2.2 (0.7-20.6) | 2.4 (0.7-36.6) | 2.5 (2.1-68.3) | 2.7 (0.0-65.7) | 2.4 (0.7-36.6) | 2.4 (0.0-68.3) |
BMI, body mass index; ECOG PS, Eastern Cooperative Oncology Group performance status; SD, standard deviation.
1 patient in dose level −1 had unknown race.
Based on local pathology laboratory reports.
Defined as stable disease or progressive disease at completion of treatment regimen preceding study entry.
Defined as refractory to front-line regimen (only received 1 prior therapy) based on medical history.
Two patients with prior autologous transplant did not respond to salvage therapy.