Patient characteristics before VEN-containing regimen
| . | VEN-R . | VEN monotherapy . | Whole cohort . |
|---|---|---|---|
| Clinico-pathologic characteristics before VEN | |||
| n | 32 | 15 | 47 |
| Age, y (median, range) | 70.5 (49-84) | 68 (47-86) | 70 (47-86) |
| Treatments (n) before VEN (including cBTKi)∗ | 2 (1-5) | 3 (1-7) | 2 (1-7) |
| Chemoimmunotherapy exposed | 28 (89%) | 14 (93%) | 42 (89%) |
| Fludarabine refractory (<PR or PD within 6 mos) | 3 (9%) | 1 (7%) | 4 (9%) |
| First cBTKi-containing therapy | |||
| Ibrutinib | 23 (72%) | 14 (93%) | 37 (79%) |
| Acalabrutinib | 1 (3%) | 0 (0%) | 1 (2%) |
| Zanubrutinib | 8 (25%) | 1 (7%) | 9 (19%) |
| Reason for BTKi cessation | |||
| PD | 25 (78%) | 13 (87%) | 38 (81%) |
| Toxicity | 7 (22%) | 2 (13%) | 9 (19%) |
| Time to progression after cBTKi initiation, mos (median, range) | 32 (6.3-83.1) | 24.0 (1.1-90.7) | 31.5 (1.1-90.7) |
| Intervening therapy between cBTKi-containing regimen and VEN | |||
| None | 29 (91%) | 13 (87%) | 42 (89%) |
| Bendamustine-R | 0 (0%) | 1 (7%) | 1 (2%) |
| Methylprednisolone-R | 0 (0%) | 1 (7%) | 1 (2%) |
| Pirtobrutinib | 3 (9%) | 0 (0%) | 3 (6%) |
| Genetics before VEN-containing regimen | |||
| IGHV unmutated | 13 of 15 (87%) | 5 of 6 (83%) | 18 of 21 (86%) |
| Genomic complexity (≥5 lesions) | 8 of 16 (50%) | 3 of 8 (38%) | 11 of 24 (46%) |
| del17p and/or TP53 mutated | 17 of 24 (71%) | 9 of 14 (64%) | 26 of 38 (68%) |
| BTKi resistance mutation(s) detected | 13 of 16 (81%) | 2 of 5 (40%) | 15 of 21 (71%) |
| Outcomes after VEN-based therapy | |||
| Best iwCLL response to VEN-based regimen | |||
| CR¶ | 6 (19%) | 3 (20%) | 9 (19%) |
| PR | 20 (63%) | 4 (27%) | 24 (51%) |
| SD | 3 (9%) | 4 (27%) | 7 (15%) |
| PD | 2 (6%) | 0 (0%) | 2 (4%) |
| Not evaluated† | 1 (3%) | 4 (27%) | 5 (11%) |
| uMRD attained in PB or BM‡ | 7 of 10 (70%) | 1 of 5 (20%) | 8 of 15 (53%) |
| Reason for VEN cessation | |||
| PD | 9 (28%) | 6 (40%) | 15 (32%) |
| Remains on VEN at last follow-up | 10 (31%) | 3 (20%) | 13 (28%) |
| Completed time-limited therapy | 6 (19%) | 0 (0%) | 6 (13%) |
| Proceeded to allo-SCT | 3 (9%) | 1 (7%) | 4 (9%) |
| Toxicity§ | 1 (3%) | 3 (20%) | 4 (9%) |
| Other|| | 3 (9%) | 2 (13%) | 5 (11%) |
| . | VEN-R . | VEN monotherapy . | Whole cohort . |
|---|---|---|---|
| Clinico-pathologic characteristics before VEN | |||
| n | 32 | 15 | 47 |
| Age, y (median, range) | 70.5 (49-84) | 68 (47-86) | 70 (47-86) |
| Treatments (n) before VEN (including cBTKi)∗ | 2 (1-5) | 3 (1-7) | 2 (1-7) |
| Chemoimmunotherapy exposed | 28 (89%) | 14 (93%) | 42 (89%) |
| Fludarabine refractory (<PR or PD within 6 mos) | 3 (9%) | 1 (7%) | 4 (9%) |
| First cBTKi-containing therapy | |||
| Ibrutinib | 23 (72%) | 14 (93%) | 37 (79%) |
| Acalabrutinib | 1 (3%) | 0 (0%) | 1 (2%) |
| Zanubrutinib | 8 (25%) | 1 (7%) | 9 (19%) |
| Reason for BTKi cessation | |||
| PD | 25 (78%) | 13 (87%) | 38 (81%) |
| Toxicity | 7 (22%) | 2 (13%) | 9 (19%) |
| Time to progression after cBTKi initiation, mos (median, range) | 32 (6.3-83.1) | 24.0 (1.1-90.7) | 31.5 (1.1-90.7) |
| Intervening therapy between cBTKi-containing regimen and VEN | |||
| None | 29 (91%) | 13 (87%) | 42 (89%) |
| Bendamustine-R | 0 (0%) | 1 (7%) | 1 (2%) |
| Methylprednisolone-R | 0 (0%) | 1 (7%) | 1 (2%) |
| Pirtobrutinib | 3 (9%) | 0 (0%) | 3 (6%) |
| Genetics before VEN-containing regimen | |||
| IGHV unmutated | 13 of 15 (87%) | 5 of 6 (83%) | 18 of 21 (86%) |
| Genomic complexity (≥5 lesions) | 8 of 16 (50%) | 3 of 8 (38%) | 11 of 24 (46%) |
| del17p and/or TP53 mutated | 17 of 24 (71%) | 9 of 14 (64%) | 26 of 38 (68%) |
| BTKi resistance mutation(s) detected | 13 of 16 (81%) | 2 of 5 (40%) | 15 of 21 (71%) |
| Outcomes after VEN-based therapy | |||
| Best iwCLL response to VEN-based regimen | |||
| CR¶ | 6 (19%) | 3 (20%) | 9 (19%) |
| PR | 20 (63%) | 4 (27%) | 24 (51%) |
| SD | 3 (9%) | 4 (27%) | 7 (15%) |
| PD | 2 (6%) | 0 (0%) | 2 (4%) |
| Not evaluated† | 1 (3%) | 4 (27%) | 5 (11%) |
| uMRD attained in PB or BM‡ | 7 of 10 (70%) | 1 of 5 (20%) | 8 of 15 (53%) |
| Reason for VEN cessation | |||
| PD | 9 (28%) | 6 (40%) | 15 (32%) |
| Remains on VEN at last follow-up | 10 (31%) | 3 (20%) | 13 (28%) |
| Completed time-limited therapy | 6 (19%) | 0 (0%) | 6 (13%) |
| Proceeded to allo-SCT | 3 (9%) | 1 (7%) | 4 (9%) |
| Toxicity§ | 1 (3%) | 3 (20%) | 4 (9%) |
| Other|| | 3 (9%) | 2 (13%) | 5 (11%) |
IGHV, immunoglobulin heavy-chain variable region gene; iwCLL, International Working Group on CLL; PR, partial response; SCC, squamous cell carcinoma; SD, stable disease; t-MN, therapy-related myeloid neoplasm.
One patient previously had undergone allo-SCT; 5 patients received a BTKi-containing regimen as first-line therapy;
Not evaluated because of early death (infection, n =3; t-MN, n =2);
uMRD, defined as <1 CLL cell per 10 000 leukocytes by flow cytometry;
Fatal infection (n = 2), fatal intracranial hemorrhage (n = 1), and recurrent neutropenia (n = 1);
t-MN (n = 2), radiotherapy for anal SCC (n =1), metastatic SCC (n =1), metastatic melanoma (n =1);
BM and CT evaluation was performed in 11 of 23 (48%) patients with clinical parameters consistent with CR, patients not assessed by both methods were classified as achieving PR.