RESUMO
Real-world evidence comparing clinical outcomes between venetoclax and Bruton tyrosine kinase inhibitors (BTKis) in patients with frontline (1 L) chronic lymphocytic leukaemia (CLL) is lacking. We compared treatment effectiveness of 1 L venetoclax plus obinutuzumab (VenO) versus BTKi-based regimens. This retrospective observational study using Optum Clinformatics Data Mart® included adult patients with CLL (≥2 outpatient or ≥1 inpatient claim) who received VenO or BTKi-based regimens in 1 L (1/2019-9/2022). Baseline characteristics were balanced using stabilised inverse probability weighting. Outcomes included duration of therapy (DoT), persistence, time to next treatment or death (TTNT-D), and time off-treatment. Among 1506 eligible patients (VenO: 203; BTKi: 1303), the median follow-up duration was 12.6 (VenO) and 16.2 months (BTKi). Median DoT for VenO was 12.3 months; persistence remained higher in VenO versus BTKi through expected 1 L fixed treatment duration. Median TTNT-D was not reached for VenO; however, more VenO- versus BTKi-treated patients had not switched therapies/experienced death through Month 12 (87.1% vs. 75.3%). Among patients that discontinued, median time to discontinuation was 11.7 vs. 5.9 months for VenO versus BTKi and median time off-treatment was 11.3 vs. 4.3 months. In this real-world study, VenO was associated with better effectiveness outcomes than BTKi-based regimens in 1 L CLL.
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PURPOSE: Real-world evidence comparing health care resource use (HRU) and costs between novel targeted therapies among patients with chronic lymphocytic leukemia (CLL) is lacking. We compared all-cause and CLL-specific HRU and costs between patients initiated on B-cell lymphoma 2 inhibitor (venetoclax)- or Bruton tyrosine kinase inhibitor (BTKi)-based regimens in the second-line (2L) setting. METHODS: This is a retrospective observational study using Optum Clinformatics Data Mart of adult patients with CLL/small lymphocytic lymphoma who received 2L venetoclax- or BTKi-based regimens (January 2018-December 2021) for the first time and had ≥one CLL diagnostic claim after 2L initiation and ≥two claims for venetoclax or BTKi. Baseline characteristics were balanced using stabilized inverse probability of treatment weights. Mean monthly cost difference (MMCD) between cohorts for all-cause and CLL-specific per patient per month (PPPM) costs was estimated. Rates of PPPM-HRU were compared between cohorts using rate ratios (RRs). RESULTS: Of 280 patients, median age 75.5 years, 64.6% and 35.4% received BTKi- versus venetoclax-based regimens, respectively. Most BTKi-treated patients received monotherapy (88.4%), whereas 62.3% of venetoclax-treated patients received combination therapy with anti-CD20 agents. The median duration of 2L therapy was 11.6 and 11.0 months for BTKi versus venetoclax cohorts, respectively. All-cause total costs were lower for venetoclax versus BTKi (MMCD [SE], $-2,497.64 [$1,006.77] in US dollars (USD); P = .01), driven by lower medication costs offsetting medical costs; trends were similar for CLL-specific estimates. Outpatient HRU was higher for venetoclax versus BTKi (RR all-cause: 1.22 versus CLL-specific: 1.64). CONCLUSION: Venetoclax was associated with total monthly cost savings versus BTKis, illustrating the economic value of time-limited venetoclax-based regimens in the 2L setting.
Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes , Leucemia Linfocítica Crônica de Células B , Sulfonamidas , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/economia , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/economia , Sulfonamidas/uso terapêutico , Sulfonamidas/economia , Masculino , Feminino , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/economia , Tirosina Quinase da Agamaglobulinemia/antagonistas & inibidores , Custos de Cuidados de Saúde , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/economiaRESUMO
The treatment landscape for chronic lymphocytic leukemia (CLL) has been transformed by the availability of Bruton's tyrosine kinase inhibitors (BTKis) and the B-cell lymphoma 2 (BCL-2) inhibitor venetoclax. Despite clinical trial data supporting these novel oral agents, evidence evaluating real-world adherence is limited. This study used 2015-2019 Medicare claims data for elderly patients with relapsed/refractory CLL to assess differences in real-world adherence and discontinuation in the 12 months after treatment initiation. In the final sample of 711 venetoclax patients and 1,566 BTKi patients, we found that those initiating venetoclax tended to be younger (mean age 75.6 [SD 6.0] vs 77.6 [SD 6.9] years, p < .001) but had poorer clinical characteristics. After risk-adjustment, the venetoclax group had higher adherence (61.9% vs. 45.4%, p < .0001) and lower discontinuation when compared to the BTKi group (28.5% vs. 47.4%, p < .001). These favorable real-world findings underscore the importance of developing well-tolerated novel combinations for older adults.
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Antineoplásicos , Leucemia Linfocítica Crônica de Células B , Linfoma de Células B , Humanos , Idoso , Estados Unidos/epidemiologia , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/patologia , Medicare , Antineoplásicos/uso terapêutico , Linfoma de Células B/tratamento farmacológico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , RecidivaRESUMO
INTRODUCTION: This study assessed treatment discontinuation patterns and reasons among chronic lymphocytic leukemia (CLL) patients initiating first-line (1L) and second-line (2L) treatments in real-world settings. MATERIALS AND METHODS: Using deidentified electronic medical records from the CLL Collaborative Study of Real-World Evidence, premature treatment discontinuation was assessed among FCR, BR, BTKi-based, and BCL-2-based regimen cohorts. RESULTS: Of 1364 1L patients (initiated in 1997-2021), 190/13.9% received FCR (23.7% discontinued prematurely); 255/18.7% received BR (34.5% discontinued prematurely); 473/34.7% received BTKi-based regimens, of whom 28.1% discontinued prematurely; and 43/3.2% received venetoclax-based regimens, of whom 16.3% discontinued prematurely (venetoclax monotherapy: 7/0.5%, of whom 42.9% discontinued; VG/VR: 36/2.6%, of whom 11.1% discontinued). The most common reasons for treatment discontinuation were adverse events (FCR: 25/13.2%; BR: 36/14.1%; BTKi-based regimens: 75/15.9%) and disease progression (venetoclax-based: 3/7.0%). Of 626 2L patients, 20/3.2% received FCR (50.0% discontinued); 62/9.9% received BR (35.5% discontinued); 303/48.4% received BTKi-based regimens, of whom 38.0% discontinued; and 73/11.7% received venetoclax-based regimens, of whom 30.1% discontinued (venetoclax monotherapy: 27/4.3%, of whom 29.6% discontinued; VG/VR: 43/6.9%, of whom 27.9% discontinued). The most common reasons for treatment discontinuation were adverse events (FCR: 6/30.0%; BR: 11/17.7%; BTKi-based regimens: 60/19.8%; venetoclax-based: 6/8.2%). CONCLUSION: The findings of this study highlight the continued need for tolerable therapies in CLL, with finite therapy offering a better tolerated option for patients who are newly diagnosed or relapsed/refractory to prior treatments.
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Antineoplásicos , Leucemia Linfocítica Crônica de Células B , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Sulfonamidas/efeitos adversos , Progressão da Doença , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antineoplásicos/uso terapêuticoRESUMO
Here we describe the rationale and design of MAJIC, a phase III, prospective, multicenter, randomized trial comparing the combination of the BTK inhibitor acalabrutinib plus the BCL2 inhibitor venetoclax versus the combination of venetoclax plus obinutuzumab as frontline treatment for chronic lymphocytic leukemia or small lymphocytic lymphoma. In both treatment arms, disease response (assessed by International Workshop on Chronic Lymphocytic Leukemia criteria) and minimal residual disease will be used to guide therapy duration, with all patients ultimately discontinuing treatment after a maximum of 2 years. The primary end point is progression-free survival. Key secondary end points include rates of undetectable minimal residual disease, overall response and overall survival. This study will address key unanswered questions in frontline chronic lymphocytic leukemia/small lymphocytic lymphoma therapy by investigating the optimal duration of finite treatment and identifying the optimal venetoclax doublet regimen.
This article describes the design of the MAJIC clinical trial, which investigates two different treatment combinations for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have not received treatment for their disease previously. Patients will be randomized (put into a group by chance) to receive either acalabrutinib + venetoclax (AV) or venetoclax + obinutuzumab (VO). VO is already an approved initial treatment option for CLL/SLL. Acalabrutinib is also an approved initial treatment option when given by itself, but the AV combination is not yet approved. We are doing this study to better understand and directly compare how well AV and VO work when used for the treatment of CLL/SLL. A test done on the blood and bone marrow called 'minimal residual disease' will be used to help guide the length of time that patients receive treatment. Clinical Trial Registration: NCT05057494 (ClinicalTrials.gov).
Assuntos
Leucemia Linfocítica Crônica de Células B , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/patologia , Estudos Prospectivos , Neoplasia Residual , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto , Ensaios Clínicos Fase III como AssuntoRESUMO
BACKGROUND/OBJECTIVE: Systemic prophylactic antibiotics have been used to reduce the rate of neurosurgical drain-related infections (DRIs) but the optimal duration is unknown. The Neurocritical Care Society Consensus Statement for External Ventricular Drain (EVD) management recommends a single antibiotic dose preoperatively. Data regarding antibiotic management for other neurosurgical drains (e.g. subgaleal and subdural drains) are lacking. Previously at our institution antibiotics were continued for the duration of drain placement. In 2016 an EVD bundle was implemented to standardize nursing care, and antibiotic duration was changed to one preoperative dose for all neurosurgical drains. The objective of this study was to compare the incidence of DRI, non-DRI, and antibiotic resistance before and after the implementation of an EVD bundle and limited duration antibiotics. PATIENTS AND METHODS: This was a single center, quasi-experimental study that included patients status post EVD or craniotomy/craniectomy with subgaleal or subdural drain placement. The pre-intervention period was June 2014 through May 2015 and the post-intervention period was January 2017 through December 2017. RESULTS: Ninety-one patients were included in the pre-intervention group and 54 in the post-intervention group. The use of limited duration antibiotics (< 48 h) was 14.3 % in the pre-intervention group and 96.3 % in the post-intervention group (p < 0.001). Five DRIs were identified in the pre-intervention group and 3 in the post-intervention group (5.5 % vs 5.6 %, p = 1.00). Of patients who developed a non-DRI, 77.5 % had a resistant non-DRI in the pre-intervention group compared to 48 % in the post-intervention group (p = 0.01). The rates of resistant DRI (80 % vs 66.7 %, p = 1.00) and Clostridium difficile infection (1.1 % vs 3.7 %, p = 0.56) were similar between groups. CONCLUSIONS: Implementation of an EVD bundle and limited duration antibiotics reduced antibiotic exposure with no associated increase in risk of DRI. Rates of resistant non-DRI were significantly lower in the post-intervention group.