NCCN Guidelines Insights: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 2.2019

Wierda, William G.; Byrd, John C.; Abramson, Jeremy S.; Bilgrami, S; Bociek, Gregory; Brander, Danielle M.; Brown, Jennifer R.; Chanan‐Khan, Asher; Chávez, Julio C.; Coutre, Steve E.; Davis, Randall S.; Fletcher, Christopher D.�M.; Hill, Brian T.; Kahl, Brad S.; Kamdar, Manali; Kaplan, Lawrence D.; Khan, Nadia; Kipps, Thomas J.; Ma, Shuo; Malek, Sami N.; Mato, Anthony R.; Mosse, Claudio A.; Neppalli, Vishala T.; Shadman, Mazyar; Siddiqi, Tanya; Stephens, Deborah M.; Wagner, Nina; Dwyer, Mary A.; Sundar, Hema

doi:10.6004/jnccn.2019.0002

Cited by 85 publications

(92 citation statements)

References 36 publications

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“…In addition, data for some variables were incomplete, principally the cytogenetic and IGHV mutational status data, as these tests were not routinely performed in Israel at the time of this study. Cytogenetic data are now more widely measured, as ibrutinib is the preferred first‐line treatment for patients with del(17p) …”

Section: Discussionmentioning

confidence: 99%

A new risk model to predict time to first treatment in chronic lymphocytic leukemia based on heavy chain immunoparesis and summated free light chain

Tadmor¹,

Braester

Dally

et al. 2019

European J of Haematology

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Background Chronic lymphocytic leukemia (CLL) is frequently accompanied by immune dysregulation. Aims In this multicenter prospective study, we investigated whether heavy + light chains (HLC: IgGκ, IgGλ, IgAκ, IgAκ, IgMκ, IgMλ) and IgG subclasses (IgG1, IgG2, IgG3, and IgG4) could be used as novel prognostic markers of immunoparesis in 105 treatment‐naïve patients with CLL. Results Heavy + light chains immunoparesis of ≥1, ≥2, and ≥3 isotypes was evident in 74 (70%), 58 (55%), and 36 (34%) patients, respectively. Severe HLC immunoparesis was identified in 40 (38%) patients. Of the IgG subclasses, IgG1 and IgG2 were most frequently suppressed, affecting 46 (44%) and 36 (34%) patients, respectively; 63 (60%) patients had low levels of at least one IgG subclass. In multivariate analysis, severe HLC immunoparesis (hazard ratio [HR]: 36.5; P = .010) and ΣFLC ≥ 70 mg/L (HR: 13.2; P = .004) were the only factors independently associated with time to first treatment (TTFT). A risk model including these variables identified patients with 0, 1, and 2 risk factors and significantly different TTFT (P < .001). Patients with two factors represented an ultra‐high‐risk group with a median TTFT of only 1.3 months. Conclusion The above findings demonstrate the potential for the use of HLC immunoparesis, together with sFLC measurements, as future prognostic biomarkers in CLL.

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Section: Discussionmentioning

confidence: 99%

A new risk model to predict time to first treatment in chronic lymphocytic leukemia based on heavy chain immunoparesis and summated free light chain

Tadmor¹,

Braester

Dally

et al. 2019

European J of Haematology

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“…According to most practice guidelines today, TP53 disruption remains the lone predictive biomarker in CLL [38][39][40][41] and should be analyzed prior to treatment initiation in all patients owing to the large body of evidence demonstrating that patients either do not respond to initial chemoimmunotherapy (CIT) or experience relapse soon after remission [42] (Table 2). The most comprehensive data addressing the predictive capacity of TP53 disruption comes from an analysis of the CLL-8 trial [43], a phase 3, randomized (1:1) study comparing treatment with fl a phase and cyclophosphamide (FC) or FC with rituximab (FCR) in 817 previously untreated patients in which Stilgenbauer et al, showed that patients with TP53 disruption experienced poorer clinical responses, minimal residual disease (MRD) negativity, progression-free survival (PFS) and OS after treatment with FC and FCR [44] and that anti-CD20 therapy added no OS benefit.…”

Section: Tp53 Disruptionmentioning

confidence: 99%

An Updated Perspective on Current Prognostic and Predictive Biomarkers in Chronic Lymphocytic Leukemia in the Context of Chemoimmunotherapy and Novel Targeted Therapy

Cohen

Bomben

Pozzo

et al. 2020

Cancers

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Chronic lymphocytic leukemia (CLL) is a heterogeneous disease with a variable clinical course. Novel biomarkers discovered over the past 20 years have revolutionized the way clinicians approach prognostication and treatment especially in the chemotherapy-free era. Herein, we review the best established prognostic and predictive biomarkers in the setting of chemoimmunotherapy (CIT) and novel targeted therapy. We propose that TP53 disruption (defined as either TP53 mutation or chromosome 17p deletion), unmutated immunoglobulin heavy chain variable region gene status (UM IGHV), NOTCH1 mutation, and CD49d expression are the strongest prognosticators of disease progression and overall survival in the field of novel biomarkers including recurrent gene mutations. We also highlight the predictive role of TP53 disruption, UM IGHV, and NOTCH1 mutation in the setting of CIT and TP53 disruption and CD49d expression in the setting of novel targeted therapy employing B-cell receptor (BCR) and B-cell lymphoma-2 (BCL2) inhibition. Finally, we discuss future directions in the field of biomarker development to identify those with relapsed/refractory disease at risk for progression despite treatment with novel therapies.

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“…48,49 This is true for patients treated with chemo(immuno)therapy or venetoclax plus rituximab. 48,49 This is true for patients treated with chemo(immuno)therapy or venetoclax plus rituximab.…”

Section: Treatment-related Biomarkersmentioning

confidence: 99%

“…Achieving undetectable MRD after receipt of therapy correlates with longer PFS and overall survival, and is considered as an endpoint in clinical trials (but not yet in daily practice). 48,49 This is true for patients treated with chemo(immuno)therapy or venetoclax plus rituximab. 10,39,40 However, the percentage of patients obtaining a complete response (a necessary condition to achieve undetectable MRD) on receipt of treatment with ibrutinib alone is small.…”

Section: Treatment-related Biomarkersmentioning

confidence: 99%

Predicting the outcome of patients with chronic lymphocytic leukemia: Progress and uncertainty

Montserrat

Gale

2019

Cancer

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Because chronic lymphocytic leukemia is a heterogeneous disease, there are considerable efforts underway to develop increasingly accurate and precise analytics with which to estimate the probability of future events such as the need for and probability of response to therapy, progression‐free survival, and survival. These analytics typically are constructed from clinical and laboratory variables. These variables often are combined into scores or staging systems, some of which are prognostic (therapy‐independent), whereas others are predictive (therapy‐dependent). Predictive variables differ with different therapies. Because response to therapy is a necessary condition for the improvement of survival, predictive biomarkers are extremely important. However, despite some progress to identify new predictive biomarkers, del(17p)/TP53 mutation remains the only widely accepted variable used to guide therapy. New laboratory techniques and analytical tools may contribute to improvements in the precision and accuracy of outcome indicators. However, there are inherent limitations when applying cohort‐based estimates to individuals within the cohort. The accuracy and precision of prediction also are limited by measurement error and chance. Ultimately, estimating outcomes requires a careful balance between clinical experience, imperfect prediction, and uncertainty.

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NCCN Guidelines Insights: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 2.2019

Cited by 85 publications

References 36 publications

A new risk model to predict time to first treatment in chronic lymphocytic leukemia based on heavy chain immunoparesis and summated free light chain

A new risk model to predict time to first treatment in chronic lymphocytic leukemia based on heavy chain immunoparesis and summated free light chain

An Updated Perspective on Current Prognostic and Predictive Biomarkers in Chronic Lymphocytic Leukemia in the Context of Chemoimmunotherapy and Novel Targeted Therapy

Predicting the outcome of patients with chronic lymphocytic leukemia: Progress and uncertainty

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