Phase III trials comparing targeted therapies including BTKi, PI3Ki, and BCL2i vs anti-CD20 monoclonal antibodies or chemoimmunotherapy regimens in patients with R/R CLL
| Treatment . | Median age (y) . | TP53 aberrations . | Prior lines of therapy, median (range) . | 3-y PFS . | Neutropenia grade ≥3 AEs . | Infection grade ≥3 AEs . | Any nonhematologic grade ≥3 AEs* . | Median follow-up . |
|---|---|---|---|---|---|---|---|---|
| IBRU (vs ofatumumab)4,5 | 67 | 32% del(17p) | 3 (1-12) | 59%† | 25% | 30% | Hypertension (9%), AF (6%), major bleeding (4%) | 59 mo (final analysis of the study) |
| IDELA-R (vs R)6,7 | 71 | 43% either del(17p) or TP53 mutation | 3 (1-12) | Median 19.4 mo | 13% | 53.6% | Diarrhea (16%), transaminitis (5%-9%), colitis (8%), pneumonitis (6%) | 18 mo (final analysis of the study) |
| VEN-R (vs BR)8,9 | 65 | 26% del(17p), 25% TP53 mutation | 2 (1-4) | 71.4% | 58.8% | 10% | TLS (2%), hyperglycemia (2%) | 23.8 mo (last update up to 4 y) |
| A (vs IDELA-R or BR)10 | 67 | 16% del(17p), 24% TP53 mutation | 1 (1-8) | Median NR | 17% | 20% | AF (1%), hemorrhage (3%), hypertension (3%) | 16 mo |
| DUV (vs ofatumumab)11 | 68 | 21% del(17p), 20% TP53 mutation | 3 (2-8) | Median 15.7 mo | 23% | 13% | Diarrhea (23%), colitis (11%), pneumonia (11%) | 22 mo |
| Treatment . | Median age (y) . | TP53 aberrations . | Prior lines of therapy, median (range) . | 3-y PFS . | Neutropenia grade ≥3 AEs . | Infection grade ≥3 AEs . | Any nonhematologic grade ≥3 AEs* . | Median follow-up . |
|---|---|---|---|---|---|---|---|---|
| IBRU (vs ofatumumab)4,5 | 67 | 32% del(17p) | 3 (1-12) | 59%† | 25% | 30% | Hypertension (9%), AF (6%), major bleeding (4%) | 59 mo (final analysis of the study) |
| IDELA-R (vs R)6,7 | 71 | 43% either del(17p) or TP53 mutation | 3 (1-12) | Median 19.4 mo | 13% | 53.6% | Diarrhea (16%), transaminitis (5%-9%), colitis (8%), pneumonitis (6%) | 18 mo (final analysis of the study) |
| VEN-R (vs BR)8,9 | 65 | 26% del(17p), 25% TP53 mutation | 2 (1-4) | 71.4% | 58.8% | 10% | TLS (2%), hyperglycemia (2%) | 23.8 mo (last update up to 4 y) |
| A (vs IDELA-R or BR)10 | 67 | 16% del(17p), 24% TP53 mutation | 1 (1-8) | Median NR | 17% | 20% | AF (1%), hemorrhage (3%), hypertension (3%) | 16 mo |
| DUV (vs ofatumumab)11 | 68 | 21% del(17p), 20% TP53 mutation | 3 (2-8) | Median 15.7 mo | 23% | 13% | Diarrhea (23%), colitis (11%), pneumonia (11%) | 22 mo |
A, acalabrutinib; AEs, adverse events; AF, atrial fibrillation; BR, bendamustine and rituximab; DUV, duvelisib; IBRU, ibrutinib; IDELA, idelalisib; NR, not reached; PFS, progression-free survival; R, rituximab; TLS, tumor lysis syndrome; VEN, venetoclax.
Focused on diverse events of clinical interest.
Median PFS 44.1 mo in the final analysis (6 years of follow-up).