Table 1.
Summary of treatment-related parameters.
| Treatments | PFS and OS (Transition Probability by 28-Day Cycle) * |
Grade 3/4 AEs (%) | Drug Cost a
(CAD/Cycle) |
References |
|---|---|---|---|---|
| 1L | ||||
| FR | Median PFS, 45.0 months (1.4%) Median OS, 105.0 months (0.6%) |
Anemia, 4 Neutropenia, 76 Thrombocytopenia, 20 Infection, 20 |
IV: C1: 3194 C2–6: 3896 Oral: C1: 3620 C2–6: 4322 |
Woyach, 2011 [38], Byrd, 2003 [41] |
| FCR | 3-year PFS, 72.9% (0.8%) 3-year OS, 91.5% (0.2%) |
Anemia, 14.6 Neutropenia, 45 Febrile neutropenia, 15.8 Thrombocytopenia, 15.2 Infection, 9.5 Atrial fibrillation, 1.2 |
IV: C1: 3071 C2–6: 3773 Oral: C1: 3069 C2–6: 3770 |
Shanafelt, 2019 [15] |
| CLB + O | Median PFS, 29.8 months (2.2%) TP53+, median PFS, 11.3 months (5.5%) 5-year OS, 66.0% (0.6%) TP53+, 30-month OS, 85.0% (0.5%) |
Anemia, 5 Neutropenia, 35 Thrombocytopenia, 11 Infection, 11 |
C1: 16,498 C2–6: 5542 |
Goede, 2018 [26], Moreno, 2019 [27], Goede, 2014 [42] |
| CLB + R | Median PFS, 15.7 months (4.0%) Median OS, 73.1 months (0.9%) |
Anemia, 4 Neutropenia, 27 Thrombocytopenia, 4 Infection, 13 |
C1: 2169 C2–6: 2871 |
Goede, 2018 [26], Goede, 2014 [42] |
| BR | Median PFS, 15.7 months (1.4%) 2-year OS, 95.0% (0.2%) |
Anemia, 12 Febrile neutropenia, 7 Infection, 15 Atrial fibrillation, 3 |
C1: 5720 C2–6: 6421 |
Woyach, 2018 [43] |
| IBRU | 5-year PFS, 73.0% (0.5%) TP53+, 1-year PFS, 87.0% (1.1%) 5-year OS, 83.0% (0.3%) TP53+, 1-year OS, 89.0% (0.9%) |
Anemia, 7 Neutropenia, 13 Infection, 12 Atrial fibrillation, 5 |
8386 | Burger, 2020 [30], Mato, 2018 [32] |
| VO | 5-year PFS, 62.6% (0.7%) TP53+, 5-year PFS, 40.6% (1.4%) 4-year OS, 85.4% (0.3%) |
Anemia, 9 Neutropenia, 53 Febrile neutropenia, 5 Thrombocytopenia, 13 Infection, 7 Atrial fibrillation, 2 |
C1: 16,532 C2: 9153 C3–6: 13,318 C7–13: 7840 |
Al-Sawaf, 2022 [19], Al-Sawaf, 2020 [44] |
| ACAL | 4-year PFS, 78.0% (0.5%) TP53+, 39-month PFS, 74.0% (0.7%) 4-year OS, 88.0% (0.2%) TP53+, 2-year OS, 95.0% (0.2%) |
Neutropenia, 11.2 Bleeding, 2.8 Atrial fibrillation, 1.1 |
7615 | Sharman, 2021 [37], Sharman, 2020 [36] |
| ACAL + O | 4-year PFS, 87.0% (0.3%) TP53+, 33-month PFS, 70.2% (1.0%) 4-year OS, 93.0% (0.1%) TP53+, 2-year OS, 95.0% (0.2%) |
Neutropenia, 30.9 Bleeding, 2.9 Atrial fibrillation, 0.6 |
C1: 7615 C2: 24,048 C3: 13,092 C8+: 7615 |
Sharman, 2021 [37], Sharman, 2020 [36] |
| 2L/3L ** | ||||
| FCR | Median PFS, 30.6 months (2.1%) 55-month OS, 60.0% (0.9%) |
Anemia, 12 Neutropenia, 42 Febrile neutropenia, 12 Thrombocytopenia, 11 Infection, 5 |
IV: C1: 3071 C2–6: 3773 Oral: C1: 3069 C2–6: 3770 |
Robak, 2010 [25] |
| BR | Median PFS, 21.6 months (2.9%) TP53+, median PFS, 14.6 months (4.3%) 5-year OS, 62.2% (0.7%) |
Anemia, 13.8 Neutropenia, 38.8 Febrile neutropenia, 9.6 Thrombocytopenia, 10.1 Infection, 8 |
C1: 5720 C2–6: 6421 |
EMA, 2020 [29], Seymour, 2018 [45] |
| IBRU | Median PFS, 42.5 months (1.5%) TP53+, median PFS, 40.6 months (1.6%) Median OS, 67.7 months (0.9%) TP53+, median OS, 61.8 months (1.0%) |
Anemia, 9 Neutropenia, 25 Thrombocytopenia, 10 Bleeding, 10 Infection, 21 Atrial fibrillation, 6 |
8386 | Munir, 2019 [31] Byrd, 2003 [46], Munir, 2019 [31] |
| V | 2-year PFS, 24.0 months (2.3%) TP53+, 1-year PFS, 72.0% (2.5%) 12-month OS, 92.0% (0.6%) TP53+, 2-year OS, 73.0% (1.2%) |
Anemia, 29 Neutropenia, 51 Febrile neutropenia, 13 Thrombocytopenia, 29 Infection, 12 |
C1: 1813 C2+: 7840 |
EMA, 2020 [29], Jones, 2018 [47] |
| VR | Median PFS, 55.1 months (1.2%) TP53+, median PFS, 47.9 months (1.3%) 5-year OS, 82.1% (0.3%) |
Anemia, 10.8 Neutropenia, 57.7 Febrile neutropenia, 3.6 Thrombocytopenia, 5.7 Infection, 17.5 |
Ramp-up: 3773 C1: 9945 C2–6: 10,647 C7–26: 7840 |
EMA, 2020 [29], Seymour, 2018 [45] |
| ACAL | 22-month PFS, 74.7% (1.2%) TP53+, 19-month PFS, 80.2% (1.1%) 12-month OS, 94.0% (0.5%) |
Anemia, 11 Neutropenia, 15 Febrile neutropenia, 0 Thrombocytopenia, 4 Infection, 5 Atrial fibrillation, 2 |
7615 | Ghia, 2020 [33] |
Descriptions: 1L: first-line, 2L: second-line, 3L: third-line, ACAL: acalabrutinib, ACAL + O: acalabrutinib in combination with obinutuzumab, AEs: adverse events, BR: bendamustine in combination with rituximab, C: cycle, CAD: Canadian dollars, CLB + O: chlorambucil in combination with obinutuzumab, CLB + R: chlorambucil in combination with rituximab, FCR: fludarabine, cyclophosphamide, rituximab, FR: fludarabine in combination with rituximab, IBRU: ibrutinib, OS: overall survival, PFS: progression-free survival, V: venetoclax, VO: venetoclax in combination with obinutuzumab, VR: venetoclax in combination with rituximab. * PFS and OS probabilities extracted from clinical trials were converted to 28-day model cycle probabilities using the conversion equations published by Fleurence (2007) [40]. ** Note that PFS and OS data for 2L and 3L are assumed to be similar. a all costs are shown in 2022 Canadian dollars.