Chronic lymphocytic leukemia international prognostic index (CLL-IPI) in patients receiving chemoimmuno or targeted therapy: a systematic review and meta-analysis

2018 ◽  
Vol 97 (10) ◽  
pp. 2005-2008 ◽  
Author(s):  
Stefano Molica ◽  
Diana Giannarelli ◽  
Rosanna Mirabelli ◽  
Luciano Levato ◽  
Tait D. Shanafelt
Keyword(s):  
Systematic Review ◽  
Targeted Therapy ◽  
Chronic Lymphocytic Leukemia ◽  
Meta Analysis ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Lymphocytic Leukemia

scholarly journals Chronic lymphocytic leukemia international prognostic index: a systematic review and meta-analysis

Blood ◽  
2018 ◽  
Vol 131 (3) ◽  
pp. 365-368 ◽  
Author(s):  
Stefano Molica ◽  
Diana Giannarelli ◽  
Rosanna Mirabelli ◽  
Luciano Levato ◽  
Neil E. Kay ◽  
...  
Keyword(s):  
Systematic Review ◽  
Chronic Lymphocytic Leukemia ◽  
Meta Analysis ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Lymphocytic Leukemia

scholarly journals Prognostic impact of prevalent chronic lymphocytic leukemia stereotyped subsets: analysis within prospective clinical trials of the German CLL Study Group (GCLLSG)

Haematologica ◽  
2019 ◽  
Vol 105 (11) ◽  
pp. 2598-2607 ◽  
Author(s):  
Sonia Jaramillo ◽  
Andreas Agathangelidis ◽  
Christof Schneider ◽  
Jasmin Bahlo ◽  
Sandra Robrecht ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Chronic Lymphocytic Leukemia ◽  
Early Stage ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Lymphocytic Leukemia ◽  
Phase Iii ◽  
Prognostic Impact ◽  
Advanced Stage ◽  
Multicenter Clinical Trials

Almost one-third of all patients with chronic lymphocytic leukemia (CLL) express stereotyped B cell receptor immunoglobulins (BcR IG) and can be assigned to distinct subsets, each with a particular BcR IG. The largest stereotyped subsets are #1, #2, #4 and #8, associated with specific clinicobiological characteristics and outcomes in retrospective studies. We assessed the associations and prognostic value of these BcR IG in prospective multicenter clinical trials reflective of two different clinical situations: i) early-stage patients (watch-and-wait arm of the CLL1 trial) (n=592); ii) patients in need of treatment, enrolled in 3 phase III trials (CLL8, CLL10, CLL11), treated with different chemo-immunotherapies (n=1861). Subset #1 was associated with del(11q), higher CLL international prognostic index (CLL-IPI) scores and similar clinical course to CLL with unmutated immunoglobulin heavy variable (IGHV) genes (U-CLL) in both early and advanced stage groups. IGHV-mutated (M-CLL) subset #2 cases had shorter time-to-first-treatment (TTFT) versus other M-CLL cases in the early-stage cohort (HR: 4.2, CI: 2-8.6, p<0.001), and shorter time-to-next-treatment (TTNT) in the advanced-stage cohort (HR: 2, CI: 1.2-3.3, p=0.005). M-CLL subset #4 was associated with lower CLL-IPI scores and younger age at diagnosis; in both cohorts, these patients showed a trend towards better outcomes versus other M-CLL. U-CLL subset #8 was associated with trisomy 12. Overall, this study shows that major stereotyped subsets have distinctive characteristics. For the first time in prospective multicenter clinical trials, subset # 2 appeared as an independent prognostic factor for earlier TTFT and TTNT and should be proposed for risk stratification of patients.

scholarly journals Safety and efficacy of Ofatumumab in chronic lymphocytic leukemia: a systematic review and meta-analysis

Hematology ◽  
2017 ◽  
Vol 22 (10) ◽  
pp. 578-584 ◽  
Author(s):  
Yougen Wu ◽  
Yang Wang ◽  
Yuting Gu ◽  
Ju Xia ◽  
Xiaoyang Kong ◽  
...  
Keyword(s):  
Systematic Review ◽  
Chronic Lymphocytic Leukemia ◽  
Meta Analysis ◽  
Lymphocytic Leukemia ◽  
Safety And Efficacy

scholarly journals Comparison between Time-Limited,Venetoclax-Based and Continuous Bruton Thyrosine Kinase Inhibitors-Based Therapy in the Upfront Treatment of Chronic Lymphocytic Leukemia (CLL):a Systematic Review and Network Meta-Analysis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 5-6
Author(s):  
Stefano Molica ◽  
Diana Giannarelli ◽  
Emili Montserrat
Keyword(s):  
Systematic Review ◽  
Chronic Lymphocytic Leukemia ◽  
Board Of Directors ◽  
Meta Analysis ◽  
Lymphocytic Leukemia ◽  
Cochrane Library ◽  
Base Case ◽  
Advisory Committees ◽  
Significant Difference ◽  
Upfront Therapy

Background: Targeted agents (TAs) have shown impressive activity in the upfront treatment of chronic lymphocytic leukemia (CLL). However, TAs have rarely been compared in head-to-head clinical trials. With this background, a systematic literature review and network meta-analysis (NMA) was performed to estimate the relative efficacy of TAs approved by the FDA and/or EMA for upfront therapy of CLL (i.e., ibrutinib, acalabrutinib, and venetoclax). Methods: A systematic search of MEDLINE, EMBASE, BioSciences Information Service, and the Cochrane Library databases was conducted. Eligible studies consisted of randomized controlled trials (RCTs) assessing the efficacy or safety of TAs in previously untreated CLL patients. Outcomes considered were hazard ratios for progression-free survival (PFS), odds ratios for overall response rate (ORR) and adverse event rates. A given treatment was considered more effective than another one when a 95 % upper confidence interval (CI) for relative risk (RR) did not cross the value 1.0 (equivalent to a Bayesian probability for this pairwise comparison p≥97.5%). Results: Among relevant RCTs, 6 met criteria of low risk for bias according to the Cochrane Handbook for Systematic Reviews of Interventions and were selected for analysis. Three studies were excluded because they lacked a common comparator arm (i.e., RESONATE2, ALLIANCE,and ECOG-ACRIN). Three trials were suitable for the base-case network analysis (i.e., ILLUMINATE, ELEVATE-TN, and CLL14). In aggregate, these trials included1336 patients and evaluated the combination of ibrutinib-obinutuzumab (IO) (ILLUMINATE trial;n=113), venetoclax-obinutuzumab (VO) (CLL14 trial;n=216) and acalabrutinib (A) single agent (ELEVATE-TN trial; n=179). Chlorambucil-obinutuzumab (CO) was the control arm across these studies (n=504). Since results of A plus obinutuzumab (AO)(n=179) in the ELEVATE-TN trial were based on a post-hoc analysis they were not included in the NMA. In terms of PFS, fixed-effect analyses comparing VO to IO (RR 1.52[0.82-2.81]), A to IO (RR 0.87 [0.47-1.61]) and A to VO (RR 0.57[0.32-1.03]) revealed that the upper limit of 95% CI for RR did exceed the 1.0 value (Fig 1). This implies a lack of significant difference in PFS for IO, VO, and acalabrutinib. Similarly, no differences with respect to ORR were found in the indirect comparison of different TAs: VO vs. IO (RR 0.98 [0.61-1.59]), A vs. IO (RR 0.90[0.55-1.48]) and A vs. VO (RR 0.92[0.60-1.40]). The analysis of treatment side effects was performed comparing in aggregate all adverse events (AEs). No differences in the frequency of AEs was observed across different TAs: VO vs. IO (RR 1.00 [0.63-1.58]), A vs. IO (RR 1.01[0.62-1.63]) and A vs. VO (RR 1.01[0.68-1.52]). The same applied when the analysis was restricted to events with grade 3-4 toxicity: VO vs. IO (RR 1.05[0.64-1.73]), A vs. IO (RR 0.73[0.43-1.24]) and A vs. VO (RR 0.69[0.44-1.09]). Conclusions: This systematic review and network meta-analysis did not identify significant differences in PFS between BTKi-and time-limited venetoclax-based treatments in CLL upfront therapy. Further trials are needed to ascertain the pros and cons of different targeted treatments. Meanwhile, treatment selection in routine clinical practice should be based on drugs' safety, cost, availability, and treatment objectives. Figure Disclosures Molica: Gilead: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Ibrutinib as initial therapy in chronic lymphocytic leukemia: A systematic review and meta‐analysis

2020 ◽  
Vol 104 (5) ◽  
pp. 512-515 ◽  
Author(s):  
Stefano Molica ◽  
Diana Giannarelli ◽  
Tycho Baumann ◽  
Emili Montserrat
Keyword(s):  
Systematic Review ◽  
Chronic Lymphocytic Leukemia ◽  
Meta Analysis ◽  
Initial Therapy ◽  
Lymphocytic Leukemia
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