Selected studies of BTKi + BCL2i ± CD20 antibody
| Study . | Regimen . | Population . | CR/CRi . | U-MRD4 . | PFS/OS . |
|---|---|---|---|---|---|
| 1L “Doublets” | |||||
| M.D. Anderson phase 2,64,65 n = 80 | I, 3 cycles; then I + V, 24 cycles; MRD–adapted I maintenance; then third year of I + V | TN; ≥65 y or high-risk genomics∗ | 78 (best) | 75 (BM-best) | 93/96 (3 y) |
| CAPTIVATE FD73 phase 2, n = 159 | I, 3 cycles; then I + V, 12 cycles; FD | TN; 18-70 y | 55.9 | 77 (PB)/60 (BM) | 95/96 (2 y) |
| CAPTIVATE MRD66 phase 2, n = 164 | I, 3 cycles; then I + V, 12 cycles; randomized, MRD–adapted consolidation and maintenance | TN; 18-70 y | 46 | 75 PB/68 BM (best) | Confirmed MRD 30 mo, 95 (placebo)/100 (I) Unconfirmed MRD, 95 (I)/97 (I + V) |
| 1L “Triplets” | |||||
| IVO,74 n = 50 | I + V + O, 14 cycles: O on d 1, 2, 8, and 15 of C1, then monthly for C2-7; I C2-14; V C3-14 | TN and RR | 32 (TN) 44 (RR) | BM: 67 (TN), 50 (RR) | NR |
| CLL2-GIVe,75 n = 41 | I + V + O, 15 cycles with response–adapted I maintenance: O, C1-6 I, C1-15; then maintenance if not in U-MRD CR; V, C1-12 (starting d22) | TN; high-risk: del(17p)/TP53mut | 59 | 88 (PB-best) | 79/93 (3 y) |
| CLL13 GAIA76 | IVO, 12 cycles | TN, excluding patients with TP53 aberrations | 231 | 92 (PB) | 91/96 (3 y) |
| AVO phase 2,77,78 n = 61 | AVO (A from C1; O cycles 2-7; V from C3). Duration 15/24 cycles, followed by MRD–adapted A maintenance beyond C24. | TN; cohort 1 (n = 37), all TN patients; cohort 2 (n = 31) | 48 | 86 (BM-best) | 93 (3 y) |
| BOVen, n = 5079 | BOVen, 8-24 cycles MRD adapted | TN | 57 | 96 (PB)/92 (BM)-best | NR |
| R/R “Doublets” | |||||
| M.D. Anderson phase 2,80 n = 80 | I + V, MRD–adapted I maintenance | R/R | NR | 67 (24 m BM) | NR |
| TAP CLARITY,67,81 n = 50 | I + V, MRD response–adapted duration (maximum 36 cycles). I maintenance in MRD+ | R/R | 78 (best) | 64 (PB)/50 (BM) | 78/91 (5 y) |
| HOVON141/Vision,82 n = 225 | I + V, MRD–adapted ibrutinib maintenance | R/R | 64 | 50 (PB)/37 (BM) | 98 (27 mo) |
| Study . | Regimen . | Population . | CR/CRi . | U-MRD4 . | PFS/OS . |
|---|---|---|---|---|---|
| 1L “Doublets” | |||||
| M.D. Anderson phase 2,64,65 n = 80 | I, 3 cycles; then I + V, 24 cycles; MRD–adapted I maintenance; then third year of I + V | TN; ≥65 y or high-risk genomics∗ | 78 (best) | 75 (BM-best) | 93/96 (3 y) |
| CAPTIVATE FD73 phase 2, n = 159 | I, 3 cycles; then I + V, 12 cycles; FD | TN; 18-70 y | 55.9 | 77 (PB)/60 (BM) | 95/96 (2 y) |
| CAPTIVATE MRD66 phase 2, n = 164 | I, 3 cycles; then I + V, 12 cycles; randomized, MRD–adapted consolidation and maintenance | TN; 18-70 y | 46 | 75 PB/68 BM (best) | Confirmed MRD 30 mo, 95 (placebo)/100 (I) Unconfirmed MRD, 95 (I)/97 (I + V) |
| 1L “Triplets” | |||||
| IVO,74 n = 50 | I + V + O, 14 cycles: O on d 1, 2, 8, and 15 of C1, then monthly for C2-7; I C2-14; V C3-14 | TN and RR | 32 (TN) 44 (RR) | BM: 67 (TN), 50 (RR) | NR |
| CLL2-GIVe,75 n = 41 | I + V + O, 15 cycles with response–adapted I maintenance: O, C1-6 I, C1-15; then maintenance if not in U-MRD CR; V, C1-12 (starting d22) | TN; high-risk: del(17p)/TP53mut | 59 | 88 (PB-best) | 79/93 (3 y) |
| CLL13 GAIA76 | IVO, 12 cycles | TN, excluding patients with TP53 aberrations | 231 | 92 (PB) | 91/96 (3 y) |
| AVO phase 2,77,78 n = 61 | AVO (A from C1; O cycles 2-7; V from C3). Duration 15/24 cycles, followed by MRD–adapted A maintenance beyond C24. | TN; cohort 1 (n = 37), all TN patients; cohort 2 (n = 31) | 48 | 86 (BM-best) | 93 (3 y) |
| BOVen, n = 5079 | BOVen, 8-24 cycles MRD adapted | TN | 57 | 96 (PB)/92 (BM)-best | NR |
| R/R “Doublets” | |||||
| M.D. Anderson phase 2,80 n = 80 | I + V, MRD–adapted I maintenance | R/R | NR | 67 (24 m BM) | NR |
| TAP CLARITY,67,81 n = 50 | I + V, MRD response–adapted duration (maximum 36 cycles). I maintenance in MRD+ | R/R | 78 (best) | 64 (PB)/50 (BM) | 78/91 (5 y) |
| HOVON141/Vision,82 n = 225 | I + V, MRD–adapted ibrutinib maintenance | R/R | 64 | 50 (PB)/37 (BM) | 98 (27 mo) |
Treatment details: for the sake of space, the details of precombination BTKi monotherapy have not been included.
1L, first-line; A, acalabrutinib; AVO, acalabrutinib/venetoclax/obinutuzumab; BM, bone marrow; BOVen, Brukinsa (zanubrutinib)/obinutuzumab/venetoclax; C1, cycle 1; CR/CRi, complete remission with or without marrow recovery; FD, fixed duration; I, ibrutinib; IVO, ibrutinib-venetoclax-obinutuzumab; NR, no response; O, Obinutuzumab; PB, peripheral blood; TN, treatment-naïve; V, venetoclax.
High-risk genomics: any of del(11q), del(17p), unmutated IgHV, or TP53 mutation.