scholarly journals Venetoclax: a real game changer in treatment of chronic lymphocytic leukemia

2020 ◽  
Vol 9 (4) ◽  
pp. IJH31
Author(s):  
Stefano Molica
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Residual Disease ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Lymphocytic Leukemia ◽  
High Rate ◽  
Clinical Activity ◽  
Orally Bioavailable ◽  
Optimal Approach ◽  
Game Changer

Venetoclax – a novel, orally bioavailable inhibitor of B-cell lymphoma-2 – has demonstrated substantial clinical activity in the treatment of chronic lymphocytic leukemia. Alone or in combination with other targeted agents, venetoclax results in high rate of durable responses and undetectable measurable residual disease. The peculiarity of venetoclax is that it allows for fixed durations of therapy of 12 months in the frontline and 24 months in the relapsed/refractory setting, with a favorable impact on compliance and pharmacoeconomics. This approach implies a change of therapeutic paradigm in chronic lymphocytic leukemia from continuous to time-fixed therapy. Nowadays, it remains challenging to identify patients suitable for the optimal approach. Clinical trials addressing the issue of continuous versus time-limited therapy are ongoing.

scholarly journals The biology behind B-cell lymphoma 2 as a target in chronic lymphocytic leukemia

2016 ◽  
Vol 7 (6) ◽  
pp. 321-329 ◽  
Author(s):  
Valentín Ortíz-Maldonado ◽  
Pablo Mozas ◽  
Julio Delgado
Keyword(s):  
Clinical Trials ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Mitochondrial Pathway ◽  
Therapeutic Agents ◽  
Lymphocytic Leukemia ◽  
Hallmarks Of Cancer ◽  
Lymphoid Malignancies

B-cell lymphoma 2 (BCL2)-type proteins are key regulators of the intrinsic or mitochondrial pathway for apoptosis. Since escape from apoptosis is one the main ‘hallmarks of cancer’, BCL2 inhibitors have emerged as promising therapeutic agents for diverse lymphoid malignancies, particularly chronic lymphocytic leukemia (CLL). Multiple clinical trials have shown efficacy of these agents in patients with relapsed/refractory disease with a favorable toxicity profile. Moreover, some clinical trials indicate that combination with monoclonal antibodies and other novel agents may enhance their effect.

scholarly journals Combination chemoimmunotherapy with pentostatin, cyclophosphamide, and rituximab shows significant clinical activity with low accompanying toxicity in previously untreated B chronic lymphocytic leukemia

Blood ◽  
2006 ◽  
Vol 109 (2) ◽  
pp. 405-411 ◽  
Author(s):  
Neil E. Kay ◽  
Susan M. Geyer ◽  
Timothy G. Call ◽  
Tait D. Shanafelt ◽  
Clive S. Zent ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Chronic Lymphocytic Leukemia ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphocytic Leukemia ◽  
Clinical Activity ◽  
Hematologic Toxicity ◽  
Color Flow ◽  
Significant Clinical Activity ◽  
Minimal Residual

Abstract Building on the prior work of use of pentostatin in chronic lymphocytic leukemia (CLL), we initiated a trial of combined pentostatin (2 mg/m2), cyclophosphamide (600 mg/m2), and rituximab (375 mg/m2) for 65 symptomatic, previously untreated patients. Of 64 evaluable patients, 34 (53%) were high Rai risk, 71% were nonmutated for the immunoglobulin heavy-chain variable region gene, 34% were CD38+, and 34% were ZAP-70+. Thirty patients (52%) had one anomaly detected by fluorescence in situ (FISH) hybridization, and 21 (36%) had complex FISH defects. Thirty-eight patients (58%) had grade 3+ hematologic toxicity but minimal transfusion needs and no major infections. Responses occurred in 58 patients (91%), with 26 (41%) complete responses (CRs), 14 (22%) nodular partial responses (nodular PRs), and 18 (28%) partial responses (PRs). Many patients with a CR also lacked evidence of minimal residual disease by 2-color flow cytometry. Examination of prognostic factors demonstrated poor response in the 3 patients with del(17p). In contrast, we found this regimen was equally effective in young versus older (> 70 years) patients and in del(11q22.3) versus other favorable prognostic factors. Thus, this novel regimen of pentostatin, cyclophosphamide, and rituximab for previously untreated patients with CLL demonstrated significant clinical activity despite poor risk-based prognoses, achievement of minimal residual disease in some, and modest toxicity.

An unusual case of indolent B-cell lymphoma with distinct chronic lymphocytic leukemia and marginal zone differentiation according to the site of involvement

2005 ◽  
Vol 46 (9) ◽  
pp. 1369-1374 ◽  
Author(s):  
Lucile Baseggio ◽  
Sophie Gazzo ◽  
Evelyne Callet-Bauchu ◽  
Alexandra Traverse-Glehen ◽  
Catherine Thieblemont ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Unusual Case ◽  
Marginal Zone ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Lymphocytic Leukemia

scholarly journals Fine-tuning front-line therapy in chronic lymphocytic leukemia

2020 ◽  
Vol 13 (3) ◽  
pp. 259-265 ◽  
Author(s):  
Jan-Paul Bohn ◽  
Dominik Wolf
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Kinase Inhibitor ◽  
Residual Disease ◽  
B Cell Lymphoma ◽  
Outcome Data ◽  
Lymphocytic Leukemia ◽  
Fine Tuning ◽  
Targeted Drugs ◽  
First Line ◽  
Good Tolerability

Summary A deeper understanding of disease biology and the advent of targeted drugs have implemented chemotherapy-free treatment options in chronic lymphocytic leukemia (CLL). With consistently superior outcome data and good tolerability, the Bruton’s kinase inhibitor ibrutinib as well as the B‑cell lymphoma 2 inhibitor venetoclax +/− CD20 antibody have recently been licensed for first-line treatment independently of TP53 status and are currently recommended as therapy of choice in most patient subgroups according to international management guidelines. Survival curves, however, have not reached a plateau and relapse due to acquired resistance or drug intolerance remain major hurdles in CLL treatment. Clinical trials currently focus on the most promising combinations and sequences of highly effective targeted drugs aimed at avoiding drug resistance by further enhancing eradication of minimal residual disease and optimizing drug tolerability. This brief review provides an update on the recently presented clinical trial data in first-line CLL at ASH 2019 and discusses clinically relevant obstacles to overcome.

scholarly journals Shared idiotype expression by chronic lymphocytic leukemia and B-cell lymphoma

Blood ◽  
1990 ◽  
Vol 76 (9) ◽  
pp. 1825-1829 ◽  
Author(s):  
M Chatterjee ◽  
M Barcos ◽  
T Han ◽  
XL Liu ◽  
Z Bernstein ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Lymphocytic Leukemia ◽  
B Cell Lymphomas ◽  
Surface Immunoglobulin ◽  
Leukemias And Lymphomas ◽  
Repetitive Pattern

Abstract Antiidiotype (Id) antibodies identify unique determinants within the surface immunoglobulin (Ig) that are present on B-cell tumors. Anti-Ids have been used for diagnosis and therapy of B-cell lymphoma and leukemia. A panel of 29 anti-Id monoclonal antibodies (MoAbs) that recognize shared idiotypes (SIds) on B-cell lymphomas was tested for reactivity with both B-cell leukemias and lymphomas. Ten of 40 (25%) cases of chronic lymphocytic leukemia (CLL) reacted with at least one of the 29 anti-SId MoAbs. Three cases reacted with more than one anti- SId MoAb, but there was no repetitive pattern of a single anti-SId MoAb reacting with a large proportion of CLL cases. In contrast, for B-cell lymphoma, in which 11 of 31 (36%) cases reacted, one anti-SId (B4–1) reacted with five of the positive cases; all were diffuse histology. Restricted anti-SId reactivity may lead to important insights into the etiology of certain B-cell lymphomas. In addition, these anti-SIds may obviate the need to develop “tailor-made” antibodies for individual patients.

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