A network meta-analysis of maintenance therapy in chronic lymphocytic leukemia

Lee, Chien-Hsing; Chen, Po-Huang; Lin, Chin; Wang, Chieh-Yung; Ho, Ching‐Liang

doi:10.1371/journal.pone.0226879

Cited by 4 publications

(3 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Overall, 138 records were retrieved: 13 fully published MAs reported PFS or OS ( Table 1 and Table 2 ) [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ] and 10 MAs reported safety outcomes ( Table 3 ) [ 8 , 9 , 11 , 15 , 18 , 19 , 20 , 21 , 22 , 23 ].…”

Section: Resultsmentioning

confidence: 99%

Comparative Clinical Value of Pharmacologic Therapies for B-Cell Chronic Lymphocytic Leukemia: An Umbrella Analysis

Marchetti

Rivela

Bertassello

et al. 2022

JCM

View full text Add to dashboard Cite

Several new drugs are progressively improving the life span of patients with B-cell chronic lymphocytic leukemia (CLL). However, the rapidly evolving standard of care precludes robust assessments of the incremental clinical value of further innovative drugs. Therefore, we systematically reviewed comparative evidence on newly authorized CLL drugs, as reported by standard and network meta-analyses (MA) published since 2016. Overall, 17 MAs addressed the relative survival or safety of naïve and/or refractory/relapsed (R/R) CLL patients. In R/R patients, therapies including BTK- and BCL2-inhibitors reported progression free survival (PFS) hazard ratios ranging from 0.08 to 0.24 (versus chemotherapy) and a significant advantage in overall survival (OS). In naïve patients, the PFS hazard ratios associated with four recent chemo-free therapies (obinutuzumab- and/or acalabrutinib-based) ranged from 0.11 to 0.61 versus current standard treatments (STs), without a significant OS advantage. Ten MAs addressed the risk of cardiovascular, bleeding, and infective events associated with BTK inhibitors, with some reporting a different relative safety in naïve and R/R patients. In conclusion, last-generation therapies for CLL consistently increase PFS, but not OS, and minimally decrease safety, as compared with STs. Based on available evidence, the patient-customized adoption of new therapies, rather than universal recommendations, seems desirable in CLL patients.

show abstract

Section: Resultsmentioning

confidence: 99%

Comparative Clinical Value of Pharmacologic Therapies for B-Cell Chronic Lymphocytic Leukemia: An Umbrella Analysis

Marchetti

Rivela

Bertassello

et al. 2022

JCM

View full text Add to dashboard Cite

show abstract

“…Previous network meta-analysis had shown that maintenance therapies achieved superior effect in prolonging progression-free survival (PFS) compared without intervention. Moreover, the therapy did not significantly increase the risk of overall serious adverse events (SAE) [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

Effect of Lenalidomide Maintenance in Chronic Lymphocytic Leukemia: A Meta-Analysis and Trial-Sequential Analysis

Jhou

Chen

et al. 2022

Current Oncology

Self Cite

View full text Add to dashboard Cite

Chronic lymphocytic leukemia (CLL) is the most common lymphoproliferative disease in adults. Despite durable responses and sustained remission rates to frontline therapy, CLL is still incurable within standard therapy and eventually relapses. Maintenance therapies aim to achieve deep remission. However, the efficacy and safety of lenalidomide maintenance are still debated. Randomized controlled trials published before March 2022 were retrieved from databases. Primary outcomes were progression-free survival (PFS) and overall survival (OS). Trial sequential analysis examined analytical power in primary outcomes. Secondary outcomes were Grade 3–4 neutropenia, treatment discontinuation (TD), serious adverse events (SAE), and fatal adverse events (FAE). Hazard (HR) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Four articles (733 patients) met the selection criteria. Lenalidomide maintenance was associated with a statistically significant effect in prolonging PFS (HR, 0.43; 95% CI, 0.28–0.68; I2 = 57%) and higher proportion of SAE (OR 4.64; 95% CI 2.96–7.26; I2 = 0%) and exhibited no difference in OS (HR, 0.62; 95% CI, 0.29–1.30; I2 = 52%) observation/placebo. It showed no significant difference compared with observation/placebo regarding Grade 3–4 neutropenia (OR 2.30; 95% CI 0.84–6.28; I2 = 81%), TD (OR 0.76; 95% CI 0.29–1.99; I2 = 84%), and FAE (OR 0.86; 95% CI 0.28–2.63; I2 = 0%). Lenalidomide maintenance can prolong PFS in CLL. Further studies should verify its effect on OS.

show abstract

“…Different CLL populations may benefit from an individualized approach that considers risk factors and prognosis (e.g. age, stage, immunoglobulin heavy chain [ IGHV ] status, del11q and del17p abnormalities, TP53 gene mutations), and treatment preferences 6‐8 . Many patients have comorbidities, which may have an adverse impact on treatment, precluding them from standard chemoimmunotherapy (CIT) and affecting OS.…”

Section: Introductionmentioning

confidence: 99%

Treatment strategies for a rapidly evolving landscape in chronic lymphocytic leukemia management

Eyre

Hori

Munir

2021

Hematological Oncology

View full text Add to dashboard Cite

With the advent of targeted therapies for chronic lymphocytic leukemia (CLL), treatment choice has expanded and patients are living longer. Careful consideration is needed regarding treatment duration and sequence, how best to meet patients' needs, balancing toxicities while improving long-term survival and maximizing depth of response. This review addresses these considerations and discusses current targeted treatment dilemmas. Targeted therapies have dramatically transformed the CLL treatment landscape. Two treatment paradigms have emerged using B-cell lymphoma 2 inhibitors (BCL2i) and Bruton's tyrosine kinase (BTK): (i) fixed duration and (ii) continuous treatment. The BCL2i venetoclax can attain deep remissions with a fixed-duration approach, resulting in high rates of undetectable minimal residual disease (uMRD) in treatment-naïve and relapsed/refractory (R/R) patients with CLL.BTKis such as ibrutinib and acalabrutinib achieve high objective response rates and long-term disease control, although they rarely attain complete response or uMRD status as monotherapy. Numerous studies are evaluating the clinical utility of BTKi and BCL2i as combination therapies, where deep remissions have been found to occur. MRD status may also be a useful marker for deciding when to stop continuous therapy, and randomized trials on MRD-guided treatment strategies are currently ongoing. The current treatment choice between continuous or fixedduration therapy should be based on comorbidities, risks, preferences, and treatment goals, whilst areas of emerging clinical interest include the potential utility of BTKi-BCL2i combination therapies, as well as an MRD-guided treatment strategies in the future.

show abstract

A network meta-analysis of maintenance therapy in chronic lymphocytic leukemia

Cited by 4 publications

References 48 publications

Comparative Clinical Value of Pharmacologic Therapies for B-Cell Chronic Lymphocytic Leukemia: An Umbrella Analysis

Comparative Clinical Value of Pharmacologic Therapies for B-Cell Chronic Lymphocytic Leukemia: An Umbrella Analysis

Effect of Lenalidomide Maintenance in Chronic Lymphocytic Leukemia: A Meta-Analysis and Trial-Sequential Analysis

Treatment strategies for a rapidly evolving landscape in chronic lymphocytic leukemia management

Contact Info

Product

Resources

About