Current Treatment of Chronic Lymphocytic Leukemia: The Diminishing Role of Chemoimmunotherapy

Roeker, Lindsey E.; Thompson, Meghan C.; Mato, Anthony R.

doi:10.1007/s40265-021-01657-0

Cited by 8 publications

(6 citation statements)

References 48 publications

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“…Still, the question of how to standardize patient access to molecular tests and ibrutinib treatment to ensure clinical evidence for a CLL treatment algorithm is reflected in policy remains. While the role of FCR diminishes to a selected subset of low-risk patients, there are not many alternative therapies in the Australian frontline setting that are also reimbursed [ 48 ]. There needs to be a reimbursement pathway driven by the clinical unmet need for effective treatment in high-risk patients, particularly IGHV -U.…”

Section: Discussionmentioning

confidence: 99%

Cost Effectiveness of Molecular Diagnostic Testing Algorithms for the Treatment Selection of Frontline Ibrutinib for Patients with Chronic Lymphocytic Leukemia in Australia

Vu,

Degeling,

Thompson

et al. 2023

Appl Health Econ Health Policy

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Background Clinical indications for ibrutinib reimbursement in Australia should consider the inclusion of patients with chronic lymphocytic leukemia (CLL) harboring prognostically unfavorable TP53/IGHV genomic aberrations. This study assessed the cost effectiveness of five first-line treatment strategies in CLL for young (aged ≤ 65 years), fit patients without significant comorbidities: (1) no testing (fludarabine, cyclophosphamide and rituximab [FCR] for all), (2) test for del(17p) only, (3) test for TP53 gene mutation status, (4) test for TP53 and IGHV gene mutation status and (5) no testing (ibrutinib for all). Method A decision analytic model (decision tree and partitioned survival model) was developed from the Australian healthcare system perspective with a lifetime horizon. Comparative treatment effects were estimated from indirect treatment comparisons and survival analysis using several studies. Costs, utility and adverse events were derived from public literature sources. Deterministic and probabilistic sensitivity analyses explored the impact of modeling uncertainties on outcomes. Results Strategy 1 was associated with 5.69 quality-adjusted life-years (QALYs) and cost 458,836 Australian dollars (AUD). All other strategies had greater effectiveness but were more expensive than Strategy 1. At the willingness-to-pay (WTP) threshold of 100,000 AUD per QALY gained, Strategy 1 was most cost effective with an estimated probability of 68.8%. Strategy 4 was cost effective between thresholds 155,000–432,300 AUD per QALY gained, and Strategy 5 >432,300 AUD per QALY gained. Conclusion Population targeting using mutation testing for TP53 and IGHV when performed with del(17p) testing specifically in the context of frontline ibrutinib choice does not make a cost-ineffective treatment into a cost-effective treatment. Supplementary Information The online version contains supplementary material available at 10.1007/s40258-023-00826-4.

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Section: Discussionmentioning

confidence: 99%

Cost Effectiveness of Molecular Diagnostic Testing Algorithms for the Treatment Selection of Frontline Ibrutinib for Patients with Chronic Lymphocytic Leukemia in Australia

Vu,

Degeling,

Thompson

et al. 2023

Appl Health Econ Health Policy

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“…Dear Editor, different clinical trials on Chronic Lymphocytic Leukemia (CLL) indicate the superiority of targeted agents (TA), as ibrutinib, acalabrutinib and venetoclax, respect to chemo-immunotherapy (CIT). To explore the clinical behavior of italian hematologist and the effective application of international guidelines, 1 we completed a survey based on two questionnaires submitted to the hematological centers involved in the Campus CLL network, in May 2020 (35 centers) and in May 2021 (42 centers).…”

Section: Role Of Chemotherapy In the Treatment Of Chronic Lymphocytic...mentioning

confidence: 99%

Role of chemotherapy in the treatment of chronic lymphocytic leukemia in the era of targeted therapies in Italy. A Campus CLL network report

Ballotta

Maccaferri

Paoli

et al. 2022

Hematological Oncology

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“…Chemotherapeutic agents, including chlorambucil (alkylating agent), fludarabine (purine analogue), and cyclophosphamide (alkylating agent), are effective treatments for leukemia. However, at therapeutic doses these chemotherapeutic agents may carry significant side effects that can limit their application, particularly in weaker or older patients [ 4 ]. With the introduction of molecularly targeted agents for specific druggable proteins that are overexpressed in leukemia, an additional safety margin is added.…”

Section: Introductionmentioning

confidence: 99%

Design and Characterization of a Novel Venetoclax-Zanubrutinib Nano-Combination for Enhancing Leukemic Cell Uptake and Long-Acting Plasma Exposure

Griffin

et al. 2023

Pharmaceutics

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Leukemia remains incurable partly due to difficulties in reaching and maintaining therapeutic drug concentrations in the target tissues and cells. Next-generation drugs targeted to multiple cell checkpoints, including the orally active venetoclax (Bcl-2 target) and zanubrutinib (BTK target), are effective and have improved safety and tolerability compared to conventional, nontargeted chemotherapies. However, dosing with a single agent frequently leads to drug resistance; asynchronous coverage due to the peak-and-trough time-course of two or more oral drugs has prevented drug combinations from simultaneously knocking out the respective drugs’ targets for sustained leukemia suppression. Higher doses of the drugs may potentially overcome asynchronous drug exposure in leukemic cells by saturating target occupancy, but higher doses often cause dose-limiting toxicities. To synchronize multiple drug target knockout, we have developed and characterized a drug combination nanoparticle (DcNP), which enables the transformation of two short-acting, orally active leukemic drugs, venetoclax and zanubrutinib, into long-acting nanoformulations (VZ-DCNPs). VZ-DCNPs exhibit synchronized and enhanced cell uptake and plasma exposure of both venetoclax and zanubrutinib. Both drugs are stabilized by lipid excipients to produce the VZ-DcNP nanoparticulate (d ~ 40 nm) product in suspension. The VZ-DcNP formulation has enhanced uptake of the two drugs (VZ) in immortalized leukemic cells (HL-60), threefold over that of its free drug counterpart. Additionally, drug-target selectivity of VZ was noted with MOLT-4 and K562 cells that overexpress each target. When given subcutaneously to mice, the half-lives of venetoclax and zanubrutinib were extended by approximately 43- and 5-fold, respectively, compared to an equivalent free VZ. Collectively, these data suggest that VZ in VZ-DcNP warrant consideration for preclinical and clinical development as a synchronized and long-acting drug-combination for the treatment of leukemia.

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Current Treatment of Chronic Lymphocytic Leukemia: The Diminishing Role of Chemoimmunotherapy

Cited by 8 publications

References 48 publications

Cost Effectiveness of Molecular Diagnostic Testing Algorithms for the Treatment Selection of Frontline Ibrutinib for Patients with Chronic Lymphocytic Leukemia in Australia

Cost Effectiveness of Molecular Diagnostic Testing Algorithms for the Treatment Selection of Frontline Ibrutinib for Patients with Chronic Lymphocytic Leukemia in Australia

Role of chemotherapy in the treatment of chronic lymphocytic leukemia in the era of targeted therapies in Italy. A Campus CLL network report

Design and Characterization of a Novel Venetoclax-Zanubrutinib Nano-Combination for Enhancing Leukemic Cell Uptake and Long-Acting Plasma Exposure

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