Italian Cytometry Society (GIC) endorsement of consensus recommendations for measurable residual disease in chronic lymphocytic leukemia

2021 ◽  
Author(s):  
Giovanni D'Arena ◽  
Silvestro Volpe ◽  
Rachele Amodeo ◽  
Virginia Tirino ◽  
Fiorella D'Auria ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Residual Disease ◽  
Lymphocytic Leukemia ◽  
Consensus Recommendations ◽  
Measurable Residual Disease

scholarly journals Measurable residual disease in chronic lymphocytic leukemia: expert review and consensus recommendations

Leukemia ◽  
2021 ◽  
Author(s):  
William G. Wierda ◽  
Andrew Rawstron ◽  
Florence Cymbalista ◽  
Xavier Badoux ◽  
Davide Rossi ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Chronic Lymphocytic Leukemia ◽  
Residual Disease ◽  
Prognostic Significance ◽  
Disease Status ◽  
Lymphocytic Leukemia ◽  
Disease Assessment ◽  
Future Studies ◽  
End Of Treatment ◽  
Measurable Residual Disease

AbstractAssessment of measurable residual disease (often referred to as “minimal residual disease”) has emerged as a highly sensitive indicator of disease burden during and at the end of treatment and has been correlated with time-to-event outcomes in chronic lymphocytic leukemia. Undetectable-measurable residual disease status at the end of treatment demonstrated independent prognostic significance in chronic lymphocytic leukemia, correlating with favorable progression-free and overall survival with chemoimmunotherapy. Given its utility in evaluating depth of response, determining measurable residual disease status is now a focus of outcomes in chronic lymphocytic leukemia clinical trials. Increased adoption of measurable residual disease assessment calls for standards for nomenclature and outcomes data reporting. In addition, many basic questions have not been systematically addressed. Here, we present the work of an international, multidisciplinary, 174-member panel convened to identify critical questions on key issues pertaining to measurable residual disease in chronic lymphocytic leukemia, review evaluable data, develop unified answers in conjunction with local expert input, and provide recommendations for future studies. Recommendations are presented regarding methodology for measurable residual disease determination, assay requirements and in which tissue to assess measurable residual disease, timing and frequency of assessment, use of measurable residual disease in clinical practice versus clinical trials, and the future usefulness of measurable residual disease assessment. Nomenclature is also proposed. Adoption of these recommendations will work toward standardizing data acquisition and interpretation in future studies with new treatments with the ultimate objective of improving outcomes and curing chronic lymphocytic leukemia.

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.

scholarly journals Advances in the biology and treatment of B-cell chronic lymphocytic leukemia

Blood ◽  
1995 ◽  
Vol 85 (2) ◽  
pp. 307-318 ◽  
Author(s):  
S O'Brien ◽  
A del Giglio ◽  
M Keating
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Residual Disease ◽  
Autologous Bone Marrow ◽  
Marrow Transplant ◽  
Lymphocytic Leukemia ◽  
Western Hemisphere ◽  
Molecular Heterogeneity ◽  
Prognostic Information ◽  
New Agents ◽  
History Of

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in the western hemisphere. Diagnosis and staging of CLL are usually straightforward, but predicting an individual patient's prognosis is still a challenge. Cytogenetic abnormalities provide important prognostic information in CLL and may show its molecular heterogeneity. A search for oncogene abnormalities continues, although no consistent defects have been identified. New agents such as fludarabine produce high complete remission rates and have generated interest in earlier treatment as a first step in a potential cure. Fludarabine also makes autologous bone marrow transplant feasible as a consolidation therapy. Immunologic abnormalities and minimal residual disease persist in most patients in remission. Combining fludarabine with other active agents and devising effective postremission strategies may change the natural history of CLL.

How I treat chronic lymphocytic leukemia after venetoclax

Blood ◽  
2021 ◽  
Author(s):  
Thomas E Lew ◽  
Constantine S. Tam ◽  
John F. Seymour
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Residual Disease ◽  
Treatment Options ◽  
Cell Receptor ◽  
Resistance Mechanisms ◽  
Lymphocytic Leukemia ◽  
Bcl2 Family ◽  
Clinical Scenarios ◽  
Car T

Venetoclax-based regimens have expanded the therapeutic options for patients with chronic lymphocytic leukemia (CLL), frequently achieving remissions with undetectable measurable residual disease (uMRD) and facilitating time-limited treatment without utilizing chemotherapy. Although response rates are high and durable disease control is common, longer-term follow-up of patients with relapsed and refractory (RR) disease, especially in the presence of TP53 aberrations, demonstrates frequent disease resistance and progression. Although the understanding of venetoclax resistance remains incomplete, progressive disease (PD) is typified by oligoclonal leukemic populations with distinct resistance mechanisms, including BCL2 mutations, upregulation of alternative BCL2 family proteins and genomic instability. Although most commonly observed in heavily pre-treated patients with disease refractory to fludarabine and harboring complex karyotype (CK), Richter transformation (RT) presents a distinct and challenging manifestation of venetoclax resistance. For patients with progressive CLL after venetoclax, treatment options include B-cell receptor pathway inhibitors (BCRis), allogeneic stem cell transplantation (SCT), chimeric antigen receptor (CAR) T-cells, and venetoclax re-treatment for those with disease relapsing after time-limited therapy. However, data to inform clinical decisions for these patients are limited. We review the biology of venetoclax resistance and outline an approach to the common clinical scenarios encountered after venetoclax-based therapy that will increasingly confront practising clinicians.

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.

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