From: Unresolved questions in selection of therapies for treatment-naïve chronic lymphocytic leukemia
Pivotal studies | All any-grade/grade ≥ 3 adverse events | Any-grade/grade ≥ 3 neutropenia; any-grade/grade ≥ 3 infection | Any-grade/grade ≥ 3 thrombocytopenia; any-grade/grade ≥ 3 bleeding | Any-grade/grade ≥ 3 diarrhoea | Any-grade/grade ≥ 3 atrial fibrillation | Any-grade/grade ≥ 3 hypertension | Treatment discontinuation due to AE Treatment related deaths |
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UK/63% (FC) vs. UK/73% (FCR)) | Neutropenia: UK/21% (FC) vs. UK/34% (FCR) Infection: UK/21% (FC) vs. UK/25% (FCR) | Thrombocytopenia: UK/11% (FC) vs. UK/7% (FCR) Bleeding: N/R | N/R | N/R | N/R | Discontinuation: UK/17% overall Death: 3% (FC) vs. 2% (FCR) | |
CLL10 [18] | 92%/UK (BR) vs. 98%/UK (FCR) | Neutropenia: 60%/59% (BR) vs. 76%/75%% (FCR) Infection: 67%/26% (BR) vs. 77%/40% (FCR) | Thrombocytopenia:18%/14% (BR) vs. 24%/21% (FCR) Bleeding: N/R | N/R | N/R | N/R | Discontinuation: 13% (BR) vs. 23% (FCR) Death: 2% (BR) vs. 5% (FCR |
N/R | Neutropenia: 16%/10% (Ib) vs. 23%/18% (Chl) Infection: N/R | Thrombocytopenia: UK/2% (Ib) vs. UK/2% (Ib) Bleeding: UK/4% (Ib) vs. UK/2% (Chl) Ext. f/up UK/7% (Ib) | 42%/4% (Ib) vs. 17%/0% (Chl) | 6%/1.5% (Ib) vs. 1%/UK (Chl) Ext. f/up—UK/6% (Ib) | 14%/4% (Ib) vs. UK/0% (Chl) Ext. f/up—UK/12% (Ib) | Discontinuation: 9% (Ib) vs. 23% (Chl) Ext. f/up—24% (Ib) Death: N/R 3% fatal cardiac events (Ib) | |
ALLIANCE 202 [53] | Haematologic: UK/41% (Ib), UK/39% (IbR), UK/61% (BR) Non-haematologic: UK/74% (Ib), UK/74% (Ib), UK/63% (BR) | Neutropenia: UK/15% (Ib), UK/21% (IbR), UK/40% (BR) Infection: UK/18% (Ib), UK/20% (IbR), UK/15% (BR) | Thrombocytopenia: UK/7% (Ib), UK/5% (IbR), UK/15% (BR) Bleeding: UK/2% (Ib), UK/4% (IbR), UK/0% (BR) | N/R | 17%/9% (Ib), 14%/6% (IbR), 3%/3% (BR) | UK/29% (Ib), UK/33% (IbR), UK/15% (BR) | Discontinuation: N/R Death: Sudden deaths 4% (Ib), 2% (IbR), 1% (BR) |
90%/68% (IbO) vs. 95%/70% (ChlO) | Neutropenia: 44%/37% (IbO) vs 63%/46% (ChlO) Infection: N/R | Thrombocytopenia: 35%/19% (IbO) vs. 25%/10% (ChlO) Bleeding: IbO: 4%/UK (IbO) vs. UK/UK (ChlO) | 34%/3% (IbO) vs 10%/0% (ChlO) Ext. f/up—35%/3% (IbO) | 7%/5% (IbO) vs. 0%/0% (ChlO) Ext. f/up—15%/6% (IbO) | 13%/4% (IbO) vs. 4%/3% (ChlO) Ext. f/up—19%/4% (IbO) | Discontinuation: 16% (IbO) vs. 9% (ChlO) Ext. f/up—22% (IbO) Death: 12.4% (IbO) vs. 2.6% (ChlO) | |
96.1%/70.2% (AO), 95.0%/49.7% (A), 98.8%/69.8% (ChlO) | Neutropenia: 31.5%/29.8% (AO), 10.6%/9.5% (A), 45%/41.4% (ChlO) Infection: UK/21% (AO), UK/14% (A), UK/8% (ChlO) | Thrombocytopenia: 12.9%/8.4% (AO), 7.3%/2.8% (A), 14.2%/11.8% (ChlO) Bleeding: 43%/2% (AO), 39%/2% (A), 12%/0% (ChlO) | 38.8%/4.5% (AO), 34.6%/0.6% (A), 21.3%/1.8% (ChlO) | 3%/UK (AO), 4%/UK (A), 1%/UK (ChlO | UK/3% (AO), UK/2% (A), UK/3% (ChlO) | Discontinuation: 11% (AO), 9% (A), 14% (ChlO) Ext. f/up: 17% (AO), 16% (A), 14% (ChlO) Death: 2.2% (AO), 3.6% (A), 6.5% (ChlO) | |
SEQUOIA [4] | 94%/53% (Z) vs. 96%/80% (BR) | Neutropenia: 16%/12% (Z) vs 57%/51% (BR) Infection: UK/16.3% (Z) vs. UK/18.9% (BR) | Thrombocytopenia: 3–4%/1–2% (Z) vs. 13%/7% (BR) Bleeding: 45%/4% (Z) vs. 11%/1.8% (BR) | 14%/1% (Z) vs. 13%/1% (BR) | 3.3%/0.4% (Z) vs. 2.6%/1.3% (BR) | 14.2%/6.3% (Z) vs. 10.6%/4.8% (BR) | Discontinuation: 8% (Z) vs. 14% (BR) Death: 4.6% (Z) vs.5.3% (BR) |
FLAIR [2] | N/R | Neutropenia: N/R Infection: 27.1%/UK (FCR) vs 33.6%/UK (IbR) | N/R | N/R | All cardiac adverse events; 1.1% (FCR) vs. 8.3% (IbR) | Discontinuation: N/R Death: Sudden deaths—2.1% (IbR) vs. 0.5% (FCR) | |
UK/80.1% (IbR) vs. UK/79.7% (FCR) | Neutropenia: UK/25.6% (IbR) vs. UK/44.9% (FCR) Ext. f/up—UK/28.4% (IbR) Infection: UK/9.1% (IbR) vs. UK/8.9% (FCR) Ext. f/up—UK/11.4% (IbR) | Thrombocytopenia: UK/3.3% (IbR) vs. UK/36.8% (FCR) Bleeding: UK/1.1% (IbR) vs. UK/0% (FCR) | UK/4.3% (IbR) vs. UK/1.3% (FCR) | 7.4%/UK (IbR) vs. 3.2%/UK (FCR) Ext. f/up—UK/4.5% (IbR) vs. UK/0% (FCR) | UK/18.8% (IbR) vs. UK/ 8.2% (FCR) | Discontinuation: N/R Ext. f/up—21.9% (IbR) (2022) Death: 1 sudden death in IbR arm | |
CLL13 [10] | 96.6%/71.3% (VenR), 98.7%/84.7% (VenO), 98.7%/82.2% (IbVenO), 98.1%/78.7% (CIT) | Neutropenia: 53.2%/46.0% (VenR), 58.8%/55.7% (VenO), 56.7%/48.5% (IbVenO), 55.6%/52.3% (CIT) Infection: 59.5%/11.4% (VenR), 68%/14% (VenO), 75.3%/22.1% (IbVenO), 60.6%/19.9% (CIT) | Thrombocytopenia: 10.1%/4.2% (VenR), 23.2%/18.4% (VenO), 29.9%/16.0% (IbVenO), 19.0%/10.2% (CIT) Bleeding: 5.1%/0.4% (VenR), 10.1%/0.4% (VenO), 27.7%/1.7% (IbVenO), 6.0%/0.5% (CIT) | N/R | 0.8%/0.4 (VenR), 0.9%/0.0% (VenO), 7.8%/2.6% (IbVenO), 1.9%/0.5% (CIT) | N/R | Discontinuation: N/R Death: N/R |
CLL14 [7] | VenO: UK/78.8% ChlO: UK/76.6% | Neutropenia: UK/52.8% (VenO) vs UK/48.1% (ChlO) Infection: UK/17.5% (VenO) vs. UK/15.0% (ChlO) | Thrombocytopenia UK/13.7% (VenO) vs. UK/15.0% (ChlO) Bleeding: N/R | UK/4.2% (VenO) vs. UK/0.5% (ChlO) | N/R | N/R | Discontinuation: N/R Death: N/R |
CAPTIVATE (FD cohort) [52] | N/R | Neutropenia: 42%/33% Infection: 67%/8% | Thrombocytopenia: 59%/13% Major bleeding: 2%/1% | 62%/3% | 4%/1% | 16%/6% | Discontinuation: N/R Death: N/R |
GLOW [34] | UK/75.5% vs. UK/69.5% | Neutropenia: 41.5%/34.9% (IbVen) vs. 58.1%/49.5% (ChlO) Infection: UK/17.0% (IbVen) vs. UK/11.5% (ChlO) | Thrombocytopenia: 11.3%/5.7% (IbVen) vs. 26.7%/20.0% (ChlO) Bleeding: N/R | 50.9%/10.4% (IbVen) vs. 12.4%/1.0% (ChlO) | 14.2%/6.6% (IbVen) vs. 1.9%/0.0% (ChlO) | 13.2%/7.5% (IbVen) vs. 4.8%/1.9% (ChlO) | Discontinuation: N/R Death: 6.6% (IbVen) vs. 1.9% (ChlO) |