First-Line Treatment of Older Patients with CLL: A New Approach in the Chemo-Free Era
Abstract
:Simple Summary
Abstract
1. Introduction
2. Literature Search
3. Older Patients
3.1. Impact of Comorbidities
3.2. Impact of CGA
4. Data from Trials
4.1. Bruton Tyrosine Kinase Inhibitors
4.2. The BCL-2 Inhibitor Venetoclax
4.3. Combination Therapy
5. Real-World Evidence
6. Cost-Effectiveness
7. Conclusions and Future Directions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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N. of Patients | Median Age (Years) | Median Follow-Up (Months) | % TP53 Aberrations | PFS and HR (95% CI) | OS | CR/ORR (%) | Reference | |
---|---|---|---|---|---|---|---|---|
BTKi vs. comparator | ||||||||
IBR vs. Chlor | 269 | 72–73 | 18.4 | 0% | 18-month PFS: IBR 90%; Chlor 52%; HR 0.16 (0.09–0.28) | 2-year OS: IBR 98%; Chlor 85% | 4/86 2/35 | [49] |
IBR vs. IBR + R vs. BR | 547 | 71 | 38 | 10% | 2-year PFS: IBR 87%; IBR + R 88%; BR 74%; HR IBR 0.37 (0.25–0.56); HR IBR + R 0.40 (0.27–0.60) | 2-year OS: IBR 90%; IBR + R 94%; BR 95% | 7/93 12/94 26/81 | [21] |
IBR + O vs. Chlor + O | 229 | 70–72 | 31.3 | 16%/20% | 30-month PFS: IBR + O 77%; CHLOR + O 16%; HR 0.23 (0.15–0.37) | 30-month OS: IBR + O 86%; CHLOR + O 85% | 19/88 8/73 | [50] |
ACALA + O, ACALA, Chlor + O | 535 | 70 | 28.3 | 9% | 2-year PFS: ACALA 87%; ACALA + O 93%; CHLOR + O 47%; HR ACALA + O 0.10 (0.06–0.17) HR ACALA 0.20, (0.13–0.30) | 2-year OS: ACALA 95%; ACALA + O 95%; CHOLOR + O 92% | 1/85 24/94 5/79 | [24] |
ZANU vs. BR | 479 | 70 years | 26.2 | 0% * | 24-month PFS: ZANU 85.5%; BR 69.5%; HR 0.42 (0.28–0.63) | 24-month OS: ZANU 94.3%; BR 94.6% | 7/95 15/85 | [15] |
Venetoclax-containing regimen vs. comparator | ||||||||
V + O vs. Chlor + O | 432 | 72–74 | 28.1 | 11.1% | 24-month PFS: VO 88.2%; CHLOR + O 64.1% HR 0.35 (0.23 to 0.53) | 24-month OS: VO 91.8%; CHLOR + O 93.3% | 49/85 33/71 | [20] |
IBR + V vs. Chlor + O | 211 | 71 | 27.7 | 4.3% | 30-month PFS: IBRU + V 80.5%; CHLOR + O 35.8%; HR 0.216 (0.131 to 0.357) | NR | 39/87 11/85 | [23] |
Trial | Median Follow-Up (Months) | AFib (*) | Hypertension | Bleeding | Infections ^ | Arthralgia | Reference |
---|---|---|---|---|---|---|---|
Resonate-2 | 18.4 | IBRU *6%/1.5%; CHLOR 0.7% | IBRU 4%; CHLOR 0% | IBRU 4% CHLOR 2% | 8% 4% | IBRU 16% **; CHLOR 7%; | [49] |
Alliance | 38 | IBR *17%/9%; IBR + R *14%/6% BR 3%/3% | IBR 29%; IBR + R 34%; BR 15% | IBR 2% IBR + R 4% BR 0% | 20% 20% 15% | NR | [21] |
iLLUMINATE | 31.3 | IBRU + O *12%/5%; CHLOR + O 0% | IBRU + O 4%; CHLOR + O 4% | NR | 11% 5% | IBRU + O 1% CHLOR + O 0% | [50] |
ACAL + O, ACAL, Chlor + O | 28.3 | A *4%; A + O *3%; CHLOR + O: *1% | A 2%; A + O 3% | A 2%; A + O 2% | 11% 3.9% 2.4% | A 0.6%; A + O 1.1% | [24] |
SEQUOIA | 26.2 | ZANU *3%; BR *3% | ZANU 6%; BR 5% | ZANU 3.5% BR 1.5% | 3% 5% | ZANU 1%; BR 0.5% | [15] |
Trial | Median Follow-Up (Months) | Infusion Related Reactions | Tumor Lysis Syndrome | Neutropenia | Infections | AFib * | Reference |
---|---|---|---|---|---|---|---|
CLL14 | 28.1 | V + O 9%; Chlor + O 10.3% | V + O 0.5%; Chlor + O 1.9% | V + O 52.8%; Chlor + O 48.1% | V + O 17.5%; Chlor + O 15.0% | NA | [20] |
GLOW | 27.7 | NA | Ibr + V 0%; Chlor + O 5.7% | Ibr + V 34.9%; Chlor + O 49.5% | Ibr + V 12.3%; Chlor + O 8.6% | Ibr + V ^ 14%/6%; Chlor + O 1.9%/0% | [23] |
Source/Country/ Reference | WTP/QALY | Treatment | Comparator | Target Population | ICER | Comments | Cost- Effective |
---|---|---|---|---|---|---|---|
NICE/U.K./114 | GBP 20,000 to 30,000 | V + O | Ibrutinib | 17p | GBP 549,699 saved per QALY lost * | V + O results in cost saving of GBP 199,622 and QALY loss of 0.363 * | YES ^ |
Chlor + O | Unsuitable for FCR/BR | NR | Dominant effect V + O vs. Chlor + O ° (more effective and less costly) | YES ^ | |||
FR/BR | Suitable for FCR/BR | GBP 47,494 vs. FCR GBP 67,445 vs. BR per QALY gained | ICERs varied widely if the upper and lower bounds of the PFS and OS HR-CI were applied | NO | |||
Dutch National Health Care Institute/ Holland/115 | EUR 50,000 | V + O | Chlor + O | Non-fit patients, uIGHV § | Incremental QALYs of 1.14 and cost saving EUR 159,276 | Dominant effect (more effective and less costly); negotiation of prices recommended | YES |
Non-fit patients, mIGHV § | NR | V + O cost saving despite limited availability of data | YES | ||||
Erasmus University Rotterdam/Holland/116 | EUR 20,000 | V + O | Chlor + O | All patients | 1.25 QALYs gained; EUR 62,316 saved | The sensitivity analyses demonstrated the robustness of these results | YES |
Stanford University/ U.S.A./117 | USD 150,000 | Ibrutinib | Chlor + O | CLL without 17p | USD 189,000 per QALY gained | A reduction of USD 20,400 per year would be required to reach the WTP of USD 150,000 | NO # |
Erasmus University Rotterdam/U.K./118 | GBP 20,000 to 30,000 | Ibrutinib | Chlor + O | CLL | GBP 75,648 per QALY gained | An adequate discount on ibrutinib is required to make it cost-effective as per the U.K. thresholds | NO # |
NICE/U.K./119 | Acalabrutinib | Chlor + O | CLL unsuitable for FRC/BR, including 17p | GBP < 30,000 per QALY gained | Considering confidential discounts | YES | |
NICE/U.K./120 | GBP 20,000 to 30,000 | Ibrutinib and venetoclax | FRC/BR | CLL suitable for FRC/BR, including 17p | GBP < 30,000 per QALY gained | Considering confidential discounts | YES |
Chlor + O and V + O | Unsuitable for FRC/BR, including 17p | GBP <30,000 per QALY gained | Dominant effect vs. Chlo + O ° | YES | |||
Acalabrutinib and ibrutinib | NR | Cost saving and a small QALY loss compared with acalabrutinib and ibrutinib | YES |
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Urso, A.; Cavazzini, F.; Ballardini, M.P.; Gambara, S.; Consolo, S.; Rigolin, G.M.; Cuneo, A. First-Line Treatment of Older Patients with CLL: A New Approach in the Chemo-Free Era. Cancers 2023, 15, 3859. https://doi.org/10.3390/cancers15153859
Urso A, Cavazzini F, Ballardini MP, Gambara S, Consolo S, Rigolin GM, Cuneo A. First-Line Treatment of Older Patients with CLL: A New Approach in the Chemo-Free Era. Cancers. 2023; 15(15):3859. https://doi.org/10.3390/cancers15153859
Chicago/Turabian StyleUrso, Antonio, Francesco Cavazzini, Maria Pia Ballardini, Silvia Gambara, Sara Consolo, Gian Matteo Rigolin, and Antonio Cuneo. 2023. "First-Line Treatment of Older Patients with CLL: A New Approach in the Chemo-Free Era" Cancers 15, no. 15: 3859. https://doi.org/10.3390/cancers15153859
APA StyleUrso, A., Cavazzini, F., Ballardini, M. P., Gambara, S., Consolo, S., Rigolin, G. M., & Cuneo, A. (2023). First-Line Treatment of Older Patients with CLL: A New Approach in the Chemo-Free Era. Cancers, 15(15), 3859. https://doi.org/10.3390/cancers15153859