Long-term Efficacy of Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia: Results of the Polish Adult Leukemia Study Group Observational Study

2020 ◽  
Vol 40 (7) ◽  
pp. 4059-4066 ◽  
Author(s):  
BARTOSZ PULA ◽  
ELZBIETA ISKIERKA-JAZDZEWSKA ◽  
MONIKA DLUGOSZ-DANECKA ◽  
AGNIESZKA SZYMCZYK ◽  
MAREK HUS ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Observational Study ◽  
Lymphocytic Leukemia ◽  
Study Group ◽  
Term Efficacy ◽  
Adult Leukemia

Long-term results of the Polish Adult Leukemia Group PALG-CLL2 phase III randomized study comparing cladribine-based combinations in chronic lymphocytic leukemia

2013 ◽  
Vol 55 (3) ◽  
pp. 606-610 ◽  
Author(s):  
Tadeusz Robak ◽  
Jerzy Z. Blonski ◽  
Joanna Gora-Tybor ◽  
Malgorzata Calbecka ◽  
Jadwiga Dwilewicz-Trojaczek ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Randomized Study ◽  
Lymphocytic Leukemia ◽  
Phase Iii ◽  
Long Term Results ◽  
Adult Leukemia ◽  
Leukemia Group

scholarly journals Final Results of a Randomized, Phase III Study of Rituximab With or Without Idelalisib Followed by Open-Label Idelalisib in Patients With Relapsed Chronic Lymphocytic Leukemia

2019 ◽  
Vol 37 (16) ◽  
pp. 1391-1402 ◽  
Author(s):  
Jeff P. Sharman ◽  
Steven E. Coutre ◽  
Richard R. Furman ◽  
Bruce D. Cheson ◽  
John M. Pagel ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Phase Iii ◽  
Extension Study ◽  
Efficacy And Safety ◽  
Term Efficacy ◽  
Phase Iii Study ◽  
Grade 3 ◽  
To Receive

PURPOSE A randomized, double-blind, phase III study of idelalisib (IDELA) plus rituximab versus placebo plus rituximab in patients with relapsed chronic lymphocytic leukemia (CLL) was terminated early because of superior efficacy of the IDELA-plus-rituximab (IDELA/R) arm. Patients in either arm could then enroll in an extension study to receive IDELA monotherapy. Here, we report the long-term efficacy and safety data for IDELA-treated patients across the primary and extension studies. PATIENTS AND METHODS Patients were randomly assigned to receive rituximab in combination with either IDELA 150 mg twice daily (IDELA/R; n = 110) or placebo (placebo/R; n = 110). Key end points were progression-free survival (PFS), overall response rate (ORR), overall survival (OS), and safety. RESULTS The long-term efficacy and safety of treatment with IDELA was assessed in 110 patients who received at least one dose of IDELA in the primary study, 75 of whom enrolled in the extension study. The IDELA/R-to-IDELA group had a median PFS of 20.3 months (95% CI, 17.3 to 26.3 months) after a median follow-up time of 18 months (range, 0.3 to 67.6 months). The ORR was 85.5% (94 of 110 patients; n = 1 complete response). The median OS was 40.6 months (95% CI, 28.5 to 57.3 months) and 34.6 months (95% CI, 16.0 months to not reached) for patients randomly assigned to the IDELA/R and placebo/R groups, respectively. Prolonged exposure to IDELA increased the incidence of all-grade, grade 2, and grade 3 or greater diarrhea (46.4%, 17.3%, and 16.4%, respectively), all-grade and grade 3 or greater colitis (10.9% and 8.2%, respectively) and all-grade and grade 3 or greater pneumonitis (10.0% and 6.4%, respectively) but did not increase the incidence of elevated hepatic aminotransferases. CONCLUSION IDELA improved PFS and OS compared with rituximab alone in patients with relapsed CLL. Long-term IDELA was effective and had an expected safety profile. No new IDELA-related adverse events were identified with longer exposure.

scholarly journals Early autologous stem cell transplantation for chronic lymphocytic leukemia: long-term follow-up of the German CLL Study Group CLL3 trial

Blood ◽  
2012 ◽  
Vol 119 (21) ◽  
pp. 4851-4859 ◽  
Author(s):  
Peter Dreger ◽  
Hartmut Döhner ◽  
Fabienne McClanahan ◽  
Raymonde Busch ◽  
Matthias Ritgen ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chronic Lymphocytic Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Lymphocytic Leukemia ◽  
Study Group ◽  
Long Term Outcome ◽  
The Impact

Abstract The CLL3 trial was designed to study intensive treatment including autologous stem cell transplantation (autoSCT) as part of first-line therapy in patients with chronic lymphocytic leukemia (CLL). Here, we present the long-term outcome of the trial with particular focus on the impact of genomic risk factors, and we provide a retrospective comparison with patients from the fludarabine-cyclophosphamide-rituximab (FCR) arm of the German CLL Study Group (GCLLSG) CLL8 trial. After a median observation time of 8.7 years (0.3-12.3 years), median progression-free survival (PFS), time to retreatment, and overall survival (OS) of 169 evaluable patients, including 38 patients who did not proceed to autoSCT, was 5.7, 7.3, and 11.3 years, respectively. PFS and OS were significantly reduced in the presence of 17p- and of an unfavorable immunoglobulin heavy variable chain mutational status, but not of 11q-. Five-year nonrelapse mortality was 6.5%. When 110 CLL3 patients were compared with 126 matched patients from the FCR arm of the CLL8 trial, 4-year time to retreatment (75% vs 77%) and OS (86% vs 90%) was similar despite a significant benefit for autoSCT in terms of PFS. In summary, early treatment intensification including autoSCT can provide very effective disease control in poor-risk CLL, although its clinical benefit in the FCR era remains uncertain. The trial has been registered with www.clinicaltrials.gov as NCT00275015.

scholarly journals Impact of long-term ibrutinib treatment on circulating immune cells in previously untreated chronic lymphocytic leukemia

2021 ◽  
Vol 102 ◽  
pp. 106520
Author(s):  
Isabelle G. Solman ◽  
Lisa K. Blum ◽  
Jan A. Burger ◽  
Thomas J. Kipps ◽  
James P. Dean ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Immune Cells ◽  
Lymphocytic Leukemia

scholarly journals Immunological and genetic kinetics from diagnosis to clinical progression in chronic lymphocytic leukemia

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Isabel Jiménez ◽  
Bárbara Tazón-Vega ◽  
Pau Abrisqueta ◽  
Juan C. Nieto ◽  
Sabela Bobillo ◽  
...  
Keyword(s):  
T Cells ◽  
Chronic Lymphocytic Leukemia ◽  
Ex Vivo ◽  
Clonal Evolution ◽  
Lymphocytic Leukemia ◽  
Clinical Progression ◽  
Molecular Changes ◽  
Main Driver ◽  
Altered Gene

Abstract Background Mechanisms driving the progression of chronic lymphocytic leukemia (CLL) from its early stages are not fully understood. The acquisition of molecular changes at the time of progression has been observed in a small fraction of patients, suggesting that CLL progression is not mainly driven by dynamic clonal evolution. In order to shed light on mechanisms that lead to CLL progression, we investigated longitudinal changes in both the genetic and immunological scenarios. Methods We performed genetic and immunological longitudinal analysis using paired primary samples from untreated CLL patients that underwent clinical progression (sampling at diagnosis and progression) and from patients with stable disease (sampling at diagnosis and at long-term asymptomatic follow-up). Results Molecular analysis showed limited and non-recurrent molecular changes at progression, indicating that clonal evolution is not the main driver of clinical progression. Our analysis of the immune kinetics found an increasingly dysfunctional CD8+ T cell compartment in progressing patients that was not observed in those patients that remained asymptomatic. Specifically, terminally exhausted effector CD8+ T cells (T-betdim/−EomeshiPD1hi) accumulated, while the the co-expression of inhibitory receptors (PD1, CD244 and CD160) increased, along with an altered gene expression profile in T cells only in those patients that progressed. In addition, malignant cells from patients at clinical progression showed enhanced capacity to induce exhaustion-related markers in CD8+ T cells ex vivo mainly through a mechanism dependent on soluble factors including IL-10. Conclusions Altogether, we demonstrate that the interaction with the immune microenvironment plays a key role in clinical progression in CLL, thereby providing a rationale for the use of early immunotherapeutic intervention.

scholarly journals Therapeutic Targets in Chronic Lymphocytic Leukemia

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3259
Author(s):  
Luca Laurenti ◽  
Dimitar G. Efremov
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Therapeutic Targets ◽  
Common Type ◽  
Lymphocytic Leukemia ◽  
Western Countries ◽  
B Cell Malignancy ◽  
Adult Leukemia ◽  
Cell Malignancy

Chronic lymphocytic leukemia (CLL) is a common B cell malignancy and is the most common type of adult leukemia in western countries [...]

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