Patient, disease, and treatment characteristics throughout first, second, and third lines of therapy in the main cohort (n = 160)
| Characteristics at diagnosis and first-line rituximab-based chemotherapy . | |
|---|---|
| Median age at diagnosis (range) | 67 (38-90) |
| Male sex, n (%) | 117 (73) |
| Blastoid/pleomorphic morphology, n (%) | 14 (9) |
| Ki67 ≥ 30%, n/N (%) | 68/117 (58) |
| TP53 mutation, n/N (%) | 4/11 (36) |
| Elevated LDH, n/N (%) | 43/115 (37) |
| Stage IV, n/N (%) | 135/158 (85) |
| ECOG performance status 0-1, n/N (%) | 111/129 (86) |
| MIPI risk group, n/N (%) | |
| High | 66/137 (48) |
| Intermediate | 45/137 (33) |
| Low | 26/137 (19) |
| First-line rituximab-based therapy, n (%) | |
| BR | 80 (50) |
| Alternating regimens (Younger/Nordic) | 31 (19) |
| Other cytarabine-based regimens∗ | 14 (9) |
| R-CHOP | 28 (18) |
| Other† | 7 (4) |
| High-dose cytarabine induction, n (%) | 40 (25) |
| Consolidative stem cell transplant, n/N (%) | 49/159 (31)‡ |
| Intensive induction/consolidation, n/N (%) | 61/159 (38) |
| Rituximab maintenance, n/N (%) | 53/145 (37) |
| Response to 1st line therapy, n/N (%) | |
| CR | 92/159 (58) |
| PR | 45/159 (28) |
| SD | 5/159 (3) |
| PD | 17/159 (11) |
| Characteristics at diagnosis and first-line rituximab-based chemotherapy . | |
|---|---|
| Median age at diagnosis (range) | 67 (38-90) |
| Male sex, n (%) | 117 (73) |
| Blastoid/pleomorphic morphology, n (%) | 14 (9) |
| Ki67 ≥ 30%, n/N (%) | 68/117 (58) |
| TP53 mutation, n/N (%) | 4/11 (36) |
| Elevated LDH, n/N (%) | 43/115 (37) |
| Stage IV, n/N (%) | 135/158 (85) |
| ECOG performance status 0-1, n/N (%) | 111/129 (86) |
| MIPI risk group, n/N (%) | |
| High | 66/137 (48) |
| Intermediate | 45/137 (33) |
| Low | 26/137 (19) |
| First-line rituximab-based therapy, n (%) | |
| BR | 80 (50) |
| Alternating regimens (Younger/Nordic) | 31 (19) |
| Other cytarabine-based regimens∗ | 14 (9) |
| R-CHOP | 28 (18) |
| Other† | 7 (4) |
| High-dose cytarabine induction, n (%) | 40 (25) |
| Consolidative stem cell transplant, n/N (%) | 49/159 (31)‡ |
| Intensive induction/consolidation, n/N (%) | 61/159 (38) |
| Rituximab maintenance, n/N (%) | 53/145 (37) |
| Response to 1st line therapy, n/N (%) | |
| CR | 92/159 (58) |
| PR | 45/159 (28) |
| SD | 5/159 (3) |
| PD | 17/159 (11) |
| Characteristics at first progression and second-line BTKi monotherapy . | |
|---|---|
| Median age (range) | 69 (38-91) |
| Mo to first progression, median (range) | 24 (<1-161) |
| Time to POD categories, n (%) | |
| POD6 | 30 (19) |
| POD6-24 | 51 (32) |
| POD>24 | 79 (49) |
| Blastoid/pleomorphic, n/N (%) | 27/88 (31) |
| Ki67 ≥ 30%, n/N (%) | 53/66 (80) |
| TP53 mutation, n/N (%) | 7/11 (64) |
| Elevated LDH, n/N (%) | 48/121 (40) |
| Stage IV, n/N (%) | 111/139 (80) |
| ECOG performance status 0-1, n/N (%) | 104/127 (82) |
| MIPI risk group, n/N (%) | |
| High | 59/113 (52) |
| Intermediate | 33/113 (29) |
| Low | 21/113 (19) |
| Months to second-line BTKi, median (range) | 25 (<1-162) |
| <24 mo to 2L BTKi, n (%) | 84 (53) |
| 2L BTK inhibitor, n (%) | |
| Ibrutinib | 134 (84) |
| Acalabrutinib | 20 (13) |
| Zanubrutinib | 3 (2) |
| TG-1701 | 3 (2) |
| Response to 2L BTKi, n/N (%) | |
| CR | 31/151 (21) |
| PR | 78/151 (52) |
| SD | 11/151 (7) |
| PD | 31/151 (21) |
| Months of 2L BTKi duration, median (range) | |
| Entire cohort | 9 (<1-72) |
| 2L BTKi ongoing at data cutoff | 16 (<1-72) |
| 2L BTKi discontinued at data cutoff | 5 (<1-57) |
| Ongoing 2L BTKi at data cutoff, n (%) | 50 (31) |
| Reason 2L BTKi termination, n/N (%) | |
| PD | 82/110 (75) |
| Toxicity§ | 18/110 (16) |
| Consolidative alloSCT | 4/110 (4) |
| Secondary primary cancer | 4/110 (4) |
| Noncompliance | 1/110 (1) |
| Sudden death cause unknown | 1/110 (1) |
| Characteristics at first progression and second-line BTKi monotherapy . | |
|---|---|
| Median age (range) | 69 (38-91) |
| Mo to first progression, median (range) | 24 (<1-161) |
| Time to POD categories, n (%) | |
| POD6 | 30 (19) |
| POD6-24 | 51 (32) |
| POD>24 | 79 (49) |
| Blastoid/pleomorphic, n/N (%) | 27/88 (31) |
| Ki67 ≥ 30%, n/N (%) | 53/66 (80) |
| TP53 mutation, n/N (%) | 7/11 (64) |
| Elevated LDH, n/N (%) | 48/121 (40) |
| Stage IV, n/N (%) | 111/139 (80) |
| ECOG performance status 0-1, n/N (%) | 104/127 (82) |
| MIPI risk group, n/N (%) | |
| High | 59/113 (52) |
| Intermediate | 33/113 (29) |
| Low | 21/113 (19) |
| Months to second-line BTKi, median (range) | 25 (<1-162) |
| <24 mo to 2L BTKi, n (%) | 84 (53) |
| 2L BTK inhibitor, n (%) | |
| Ibrutinib | 134 (84) |
| Acalabrutinib | 20 (13) |
| Zanubrutinib | 3 (2) |
| TG-1701 | 3 (2) |
| Response to 2L BTKi, n/N (%) | |
| CR | 31/151 (21) |
| PR | 78/151 (52) |
| SD | 11/151 (7) |
| PD | 31/151 (21) |
| Months of 2L BTKi duration, median (range) | |
| Entire cohort | 9 (<1-72) |
| 2L BTKi ongoing at data cutoff | 16 (<1-72) |
| 2L BTKi discontinued at data cutoff | 5 (<1-57) |
| Ongoing 2L BTKi at data cutoff, n (%) | 50 (31) |
| Reason 2L BTKi termination, n/N (%) | |
| PD | 82/110 (75) |
| Toxicity§ | 18/110 (16) |
| Consolidative alloSCT | 4/110 (4) |
| Secondary primary cancer | 4/110 (4) |
| Noncompliance | 1/110 (1) |
| Sudden death cause unknown | 1/110 (1) |
| Characteristics of third-line therapy (after BTKi discontinuation) . | |
|---|---|
| Third-line therapy, n/N (%) | |
| Supportive care (steroids, radiation) | 48/110 (44) |
| CHOP (± rituximab) | 13/110 (12) |
| Venetoclax | 11/110 (9) |
| Bendamustine (± rituximab) | 10/110 (9) |
| Lenalidomide | 8/110 (7) |
| Bortezomib | 4/110 (4) |
| Novel BTK inhibitor | 4/110 (4) |
| Other‖ | 12/110 (11) |
| Type of third-line systemic therapy | |
| Chemotherapy/rituximab-based | 30/62 |
| Targeted therapy/novel agent | 32/62 |
| Intensive therapy (third line or later), n | |
| CAR T-cell therapy | 4 |
| Autologous stem cell transplant | 2 |
| Allogeneic stem cell transplant | 1 |
| Characteristics of third-line therapy (after BTKi discontinuation) . | |
|---|---|
| Third-line therapy, n/N (%) | |
| Supportive care (steroids, radiation) | 48/110 (44) |
| CHOP (± rituximab) | 13/110 (12) |
| Venetoclax | 11/110 (9) |
| Bendamustine (± rituximab) | 10/110 (9) |
| Lenalidomide | 8/110 (7) |
| Bortezomib | 4/110 (4) |
| Novel BTK inhibitor | 4/110 (4) |
| Other‖ | 12/110 (11) |
| Type of third-line systemic therapy | |
| Chemotherapy/rituximab-based | 30/62 |
| Targeted therapy/novel agent | 32/62 |
| Intensive therapy (third line or later), n | |
| CAR T-cell therapy | 4 |
| Autologous stem cell transplant | 2 |
| Allogeneic stem cell transplant | 1 |
BR, bendamustine and rituximab; CR, complete response; ECOG, Eastern Cooperative Oncology Group; LDH, lactate dehydrogenase; PR, partial response; R-CHOP, rituximab-cyclophosphamide-hydroxydaunorubicin-vincristine-prednisone.
7 R-HyperCVAD, 4 R-BAC, 2 R-DHAP, 1 iHDS regimen.
2 R-chlorambucil, 2 R-CVP, 1 FR, 1 R2, 1 unknown.
48 autologous SCT, 1 alloSCT.
5 cardiac/atrial fibrillation, 4 bleeding, 4 infection, 1 dyspnea, 1 pulmonary embolism, 1 thrombocytopenia, 1 fatigue, 1 diarrhea.
2 cytarabine, 2 BAC (+/− rituximab), 2 acalabrutinib, 1 R-ICE, 1 rituximab, 1 chlorambucil, 1 bispecific antibody, 1 CD47 antibody, 1 direct to CAR T-cell therapy.