Chronic Lymphocytic Leukemia in the Elderly: Epidemiology and Proposed Patient-Related Approach

2015 ◽  
Vol 22 (4_suppl) ◽  
pp. 3-6 ◽  
Author(s):  
Lodovico Balducci ◽  
Dawn Dolan
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
The Elderly ◽  
Lymphocytic Leukemia ◽  
Related Approach

Comparative Efficacy of First-Line Chemotherapy-Free Combinations in Chronic Lymphocytic Leukemia (CLL): A Network Meta-Analysis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 25-26
Author(s):  
Philip A Haddad ◽  
Nowell Ganey ◽  
Kevin M. Gallagher
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
English Language ◽  
Conflicts Of Interest ◽  
Residual Disease ◽  
Meta Analysis ◽  
The Elderly ◽  
Lymphocytic Leukemia ◽  
First Line ◽  
Significant Difference ◽  
Anti Cd20

Introduction: Chronic Lymphocytic Leukemia (CLL) is an incurable B-cell malignancy which disproportionately affects the elderly. Although first-line chemoimmunotherapy (CIT) improved CLL clinical outcomes, recent randomized trials revealed superior outcomes with novel chemotherapy-free combinations (CFC) incorporating anti-CD20 monoclonal antibodies and inhibitors of BTK or Bcl-2. So far, these CFC have not been compared head-to-head. We conducted this network meta-analysis to evaluate their relative efficacy to each other. Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of English language; diagnosis of CLL; trials that explored the efficacy of first-line CFC with Obinutuzumab (O), Rituximab (R), Ibrutinib (IB), Acalabrutinib (ACAL), Venetoclax (VEN) compared to standard CIT that included Chlorambucil (CHLOR) with either R or O, Bendamustine+Rituximab, or Fludarabine+ Cyclophosphamide+R; and phase 3 randomized studies reporting responses, progression, death, and adverse (AE) events. A frequentists network meta-analysis was conducted using netmeta package and random-effects model. Results: Five studies comprising a total of 2,272 participants were included. When O-based CFC data was analyzed, only ACAL-O had a significant lower relative risk (RR) of progression and death (P&D). There were no significant differences with respect to overall response rates (ORR), complete remission (CR), minimal residual disease (MRD), or grade >3 adverse events (Grd3+) among O-based CFC. When R-based CFC data was analyzed, IB and IB-R were not different with respect to RR of P&D, ORR, CR, MRD, or Grd3+. When the data was analyzed as CFC versus combined CIT, only ACAL-O was found to be significantly superior to other O- and R-based CFC with respect to RR of P&D. ORR and Grad3+ rates of O- and R-based CFC were not significantly different. While ACAL-O, IB-O, and VEN-O had superior CR and MRD rates compared to other CFC, there were no significant differences among each other. Conclusions: This network meta-analysis is the first to compare and rank first-line CFC therapies in CLL. It indicates that ACAL-O has a superior profile having the lowest RR of P&D without significant difference in Grd3+ among CFC. Disclosures No relevant conflicts of interest to declare.

Bendamustine in the Treatment of Chronic Lymphocytic Leukemia -Consistent Superiority Over Chlorambucil in Elderly Patients and Across Clinically Defined Risk Groups.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2367-2367 ◽  
Author(s):  
Wolfgang Ulrich Knauf ◽  
Toshko Lissitchkov ◽  
Ali Aldaoud ◽  
Anna Liberati ◽  
Javier Loscertales ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Remission Rate ◽  
Risk Groups ◽  
The Elderly ◽  
Lymphocytic Leukemia ◽  
Phase Iii ◽  
Response To Treatment ◽  
Open Label ◽  
Significant Difference ◽  
Binet Stage

Abstract Abstract 2367 Poster Board II-344 Introduction: Bendamustine is a purine analog/alkylator hybrid agent with a unique mechanism of action, which has shown good clinical efficacy and acceptable tolerability in various hematological malignancies. Chronic lymphocytic leukemia (CLL) is a disease of the elderly, and presents with a variety of clinical characteristics which influence the prognosis. We analyzed tolerability and efficacy of bendamustine (BEN) in comparison to chlorambucil (CLB) in clinical risk groups defined by age and specific indicators of disease activity. Patients and Methods: The efficacy and safety of BEN and CLB have been compared in a randomized, open-label, multicenter, phase III trial in patients with previously untreated advanced (Binet stage B/C) CLL. Patients were randomized to receive BEN (100 mg/m2 on days 1 + 2) or CLB (0.8 mg/kg on days 1 and 15) for up to 6 treatment cycles. The primary endpoints were overall remission rate (ORR), which was defined as complete or partial response, and progression-free survival (PFS). Secondary endpoints included overall survival (OS) and safety. The response to treatment was evaluated by a blinded Independent Response Assessment Committee. Results: A total of 319 patients were randomized (162 bendamustine, 157 chlorambucil), of whom all were included in the efficacy analysis, while 312 were evaluable for safety. Median age was 64 years (35 to 78). The median number of treatment cycles was 6 in both study arms, regardless of an age above or below 65 years. The median observation time was 35 months. ORR was significantly higher with BEN than with CLB (68% versus 31%, P<0.0001). The median PFS was 21.6 months with BEN and 8.3 months with CLB (P<0.0001). So far, there is no difference in OS (median not reached with BEN versus 65.4 months with CLB; p = 0.16). No significant difference in the remission rates became apparent when comparing patients below and above the age of 65 years (ORR 71.6 % versus 63.5 % with BEN, p>0.3; and 28.4 % versus 32.5 % with CLB, p>0.6). PFS was not influenced by age above 65 years, stage of disease (Binet stage B versus C), or elevated LDH. However, patients without B symptoms had a longer median PFS with BEN than those patients with B symptoms (30.4 months versus 17.7 months; p<0.0001), whereas median PFS was not affected by the presence of B symptoms in patients with CLB (8.9 months in both patient groups). Conclusion: This study has shown that bendamustine offers significantly greater efficacy than chlorambucil in the elderly and across clinically defined major risk groups, even in the presence of B symptoms. BEN should be considered as first-line chemotherapy for patients with advanced CLL. Disclosures: Knauf: mundipharma: Consultancy, Honoraria; cephalon: Consultancy, Honoraria. Klein:mundipharma: Consultancy, Honoraria. Merkle:mundipharma: Consultancy, Honoraria. Montillo:mundipharma Italy: Consultancy, Research Funding.

Features of the overexpressed V1-69 genes in the unmutated subset of chronic lymphocytic leukemia are distinct from those in the healthy elderly repertoire

Blood ◽  
2003 ◽  
Vol 101 (8) ◽  
pp. 3082-3084 ◽  
Author(s):  
Kathleen N. Potter ◽  
Jenny Orchard ◽  
Eustacia Critchley ◽  
C. Ian Mockridge ◽  
Annette Jose ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
The Elderly ◽  
Immunoglobulin M ◽  
Lymphocytic Leukemia ◽  
Cell Repertoire ◽  
Healthy Elderly ◽  
B Cell Repertoire ◽  
Cdr3 Length ◽  
Worse Prognosis

Abstract Chronic lymphocytic leukemia (CLL) comprises 2 subsets, distinguished by expression of unmutated or mutated VHgenes, with the former having a worse prognosis. Biased usage of the V1-69 gene is found in unmutated cases and is combined with selected D gene segments and JH6. It is controversial whether this is a CLL-associated feature or mirrors the normal B-cell pattern. Since CLL is a disease of the elderly, where changes in the B-cell repertoire may occur, we have analyzedV1-69 usage in the elderly (older than 75 years) population. Using monoclonal antibody (MoAb) G6, specific for 51p1-related V1-69 alleles, we found no increased expression with age. In 51p1-encoded immunoglobulin M (IgM), complementarity-determining region 3 (CDR3) length and frequency of D and JH genes were similar to those in the healthy young and distinct from those in CLL. These findings support the concept that CLL arises from B cells driven by antigen/superantigen and is not a stochastic event in the elderly B-cell population.

scholarly journals The Tumor Microenvironment-Dependent Transcription Factors AHR and HIF-1α Are Dispensable for Leukemogenesis in the Eµ-TCL1 Mouse Model of Chronic Lymphocytic Leukemia

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4518
Author(s):  
Susanne Gonder ◽  
Anne Largeot ◽  
Ernesto Gargiulo ◽  
Sandrine Pierson ◽  
Iria Fernandez Botana ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Tumor Microenvironment ◽  
Chronic Lymphocytic Leukemia ◽  
Mouse Model ◽  
Hypoxia Inducible Factor ◽  
The Elderly ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Knock Out

Chronic lymphocytic leukemia (CLL) is the most frequent leukemia in the elderly and is characterized by the accumulation of mature B lymphocytes in peripheral blood and primary lymphoid organs. In order to proliferate, leukemic cells are highly dependent on complex interactions with their microenvironment in proliferative niches. Not only soluble factors and BCR stimulation are important for their survival and proliferation, but also the activation of transcription factors through different signaling pathways. The aryl hydrocarbon receptor (AHR) and hypoxia-inducible factor (HIF)-1α are two transcription factors crucial for cancer development, whose activities are dependent on tumor microenvironment conditions, such as the presence of metabolites from the tryptophan pathway and hypoxia, respectively. In this study, we addressed the potential role of AHR and HIF-1α in chronic lymphocytic leukemia (CLL) development in vivo. To this end, we crossed the CLL mouse model Eµ-TCL1 with the corresponding transcription factor-conditional knock-out mice to delete one or both transcription factors in CD19+ B cells only. Despite AHR and HIF-1α being activated in CLL cells, deletion of either or both of them had no impact on CLL progression or survival in vivo, suggesting that these transcription factors are not crucial for leukemogenesis in CLL.

scholarly journals Impact of Age on Outcomes After Initial Therapy With Chemotherapy and Different Chemoimmunotherapy Regimens in Patients With Chronic Lymphocytic Leukemia: Results of Sequential Cancer and Leukemia Group B Studies

2013 ◽  
Vol 31 (4) ◽  
pp. 440-447 ◽  
Author(s):  
Jennifer A. Woyach ◽  
Amy S. Ruppert ◽  
Kanti Rai ◽  
Thomas S. Lin ◽  
Susan Geyer ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Chronic Lymphocytic Leukemia ◽  
Older Patients ◽  
Progression Free Survival ◽  
The Elderly ◽  
Initial Therapy ◽  
Routine Care ◽  
Lymphocytic Leukemia ◽  
Age Group ◽  
Group B

Purpose Chronic lymphocytic leukemia (CLL) is a disease of the elderly, yet few clinical trials include a significant number of older patients, and outcomes after specific therapies can be different depending on age. Patients and Methods We examined patients enrolled onto successive first-line CALGB CLL trials to determine whether efficacy of regimens varied by age, focusing on ideal chemotherapy choice and benefit of immunotherapy addition to chemotherapy in older patients. Regimens included chlorambucil, fludarabine, fludarabine plus rituximab (FR), fludarabine with consolidation alemtuzumab, and FR with consolidation alemtuzumab. Results A total of 663 patients were evaluated for response, progression-free survival (PFS), and overall survival (OS) by age group. Interaction effects of fludarabine versus chlorambucil by age group (PFS, P = .046; OS, P = .006) showed that among patients younger than 70 years, PFS and OS was improved with fludarabine over chlorambucil (PFS: hazard ratio [HR] = 0.6, 95% CI, 0.5 to 0.8; OS: HR = 0.7, 95% CI, 0.5 to 0.9), but not in older adults (PFS, HR = 1.0, 95% CI, 0.6 to 1.7; OS: HR = 1.5, 95% CI, 0.9 to 2.3). In contrast, FR improved outcomes relative to fludarabine, irrespective of age (PFS: HR = 0.6, 95% CI, 0.4 to 0.7; OS: HR = 0.7, 95% CI, 0.5 to 0.9). Alemtuzumab consolidation did not provide benefit over similar regimens without alemtuzumab (P > .20), irrespective of age. Conclusion These data support the use of chlorambucil as an acceptable treatment for many older patients with CLL and suggest rituximab is beneficial regardless of age. These findings bear relevance to both routine care of CLL patients 70 years and older and also future clinical trials in this population.

Transplant in Chronic Lymphocytic Leukemia: To Do It or Not and If So, When and How?

2012 ◽  
pp. 399-404
Author(s):  
John G. Gribben
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Treatment Options ◽  
The Elderly ◽  
Underlying Disease ◽  
Lymphocytic Leukemia ◽  
Major Focus ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Graft Versus Leukemia ◽  
Related Mortality

Overview: Most patients with chronic lymphocytic leukemia (CLL) have an indolent clinical course, but the disease remains incurable with standard therapy and the prognosis is dismal for those patients with disease refractory to available treatment options. The only potentially curative treatment is allogeneic hematopoietic stem cell transplantation (SCT), but since CLL is a disease of elderly patients, few patients are candidates for myeloablative allogeneic SCT. Although autologous SCT is feasible and has low treatment-related mortality, it is not curative. The widespread adoption of reduced-intensity conditioning (RIC) allogeneic SCT has made this approach applicable to the elderly patient population with CLL. This approach relies on the documented graft-versus-leukemia (GVL) effect and is strong in CLL. Steps to further decrease the morbidity and mortality of the RIC SCT and in particular to reduce the incidence of chronic extensive graft-versus-host disease (GVHD) remain a major focus. Many potential treatments are available for CLL, and appropriate patient selection and SCT timing remain controversial and the focus of ongoing clinical trials. The use of SCT must always be weighed against the risk of the underlying disease, particularly in a setting where improvements in treatment are leading to improved outcome. The major challenge remains how to identify which patients with CLL merit this approach and where in the treatment course this treatment can be applied optimally.

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