Contributions
Abstract: PB1868
Type: Publication Only
Background
Clinical heterogeneity of chronic lymphocytic leukemia (CLL) ranges from an indolent course to a very aggressive disease, while some patients never need treatment whilst many others require multiple lines of therapy during their lifetime and often die from disease. Integration between biological and clinical findings, with particular reference to innovative prognostic markers, is an increasingly pressing need for a risk stratification tool, useful for predicting disease outcome. Translation on real life setting and into everyday care is a real proposal in helping physicians to make better decisions.
Aims
To determine and analyze the most relevant biological and clinical characteristics of a multicentric real life CLL cohort and their impact on overall survival (OS) and time to progression (TTP), comparing with those reported in the literature.
Methods
A multicentric real life cohort of 273 unselected CLL patients in different clinical Binet stage were retrospectively analyzed for IGHV status, CD38 expression, NOTCH1 mutation (mut), FISH (del13q, tris12, del11q, del17p), TP53 mutational status. A large part of patients (n°190, 70%), have been included in a clinical research project currently in progress, applying ultra-deep Next Generation Sequencing (NGS), with a major aim to point out new possible prognostic or predictive biological markers (data in progress). All patient, 114 untreated (42%) and 159 treated patients (58%), have been diagnosed from 01/1988 to 01/2018, with a long term follow up (median: 89.2 months; range: 2-343). Biological and clinical patient characteristics are summarized in table 1. All data have been statistically analyzed using Prism 4.
Results
We investigated OS in patients with stage A (107.7 months), stage B (75.5 months) and C (70.1 months), defined at diagnosis (p< 0.001). Median time to progression (TTP) was 52 months for all treated patients, regardless of Binet stage at diagnosis. Moreover, IGHV mutational status was analyzed at diagnosis in 171 (63%) patients (unmutated: 22%; mutated: 78%), reporting statistically significant differences in median OS, regardless of treatment (95.3 months and 89.2 months, respectively; p<0.001). CD38 expression was evaluated in 191 patients (70%), analyzed and integrated with FISH aberrations and IGHV status. FISH analysis was overall performed in 238 samples (before first line therapy: n°200; relapsed/refractory: n° 38), identifying a small group (7%) with multiple aberrations and unfavorable prognosis. NOTCH1 c.7544_7545delCT mutations were investigated in 207 DNA samples (76%). NOTCH1-mut was detected in 23 patients (11%) and correlated with tris12 and IGVH status, analyzing impact on overall survival (OS). Only 9% of NOTCH1 mut developed Richter syndrome with fatal outcome, confirming a worse prognostic role characterized by chemoresistance and rapid disease kinetics.
Conclusion
We choose to emphasize our real life data related to IGHV, FISH aberrations and NOTCH1 mut, not yet widely applied in everyday care, confirming the need for early identification of well-known biological and clinical findings. Interesting results related to IGHV and OS must be validated through large prospective cohort study, suggesting a clue for possible other biological factors and encouraging the introduction of innovative genetic lesion analysis (ie, NGS), with the aim of selecting high risk vs low risk patients.
Session topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical
Keyword(s): Chronic Lymphocytic Leukemia, FISH, IGH, Notch
Abstract: PB1868
Type: Publication Only
Background
Clinical heterogeneity of chronic lymphocytic leukemia (CLL) ranges from an indolent course to a very aggressive disease, while some patients never need treatment whilst many others require multiple lines of therapy during their lifetime and often die from disease. Integration between biological and clinical findings, with particular reference to innovative prognostic markers, is an increasingly pressing need for a risk stratification tool, useful for predicting disease outcome. Translation on real life setting and into everyday care is a real proposal in helping physicians to make better decisions.
Aims
To determine and analyze the most relevant biological and clinical characteristics of a multicentric real life CLL cohort and their impact on overall survival (OS) and time to progression (TTP), comparing with those reported in the literature.
Methods
A multicentric real life cohort of 273 unselected CLL patients in different clinical Binet stage were retrospectively analyzed for IGHV status, CD38 expression, NOTCH1 mutation (mut), FISH (del13q, tris12, del11q, del17p), TP53 mutational status. A large part of patients (n°190, 70%), have been included in a clinical research project currently in progress, applying ultra-deep Next Generation Sequencing (NGS), with a major aim to point out new possible prognostic or predictive biological markers (data in progress). All patient, 114 untreated (42%) and 159 treated patients (58%), have been diagnosed from 01/1988 to 01/2018, with a long term follow up (median: 89.2 months; range: 2-343). Biological and clinical patient characteristics are summarized in table 1. All data have been statistically analyzed using Prism 4.
Results
We investigated OS in patients with stage A (107.7 months), stage B (75.5 months) and C (70.1 months), defined at diagnosis (p< 0.001). Median time to progression (TTP) was 52 months for all treated patients, regardless of Binet stage at diagnosis. Moreover, IGHV mutational status was analyzed at diagnosis in 171 (63%) patients (unmutated: 22%; mutated: 78%), reporting statistically significant differences in median OS, regardless of treatment (95.3 months and 89.2 months, respectively; p<0.001). CD38 expression was evaluated in 191 patients (70%), analyzed and integrated with FISH aberrations and IGHV status. FISH analysis was overall performed in 238 samples (before first line therapy: n°200; relapsed/refractory: n° 38), identifying a small group (7%) with multiple aberrations and unfavorable prognosis. NOTCH1 c.7544_7545delCT mutations were investigated in 207 DNA samples (76%). NOTCH1-mut was detected in 23 patients (11%) and correlated with tris12 and IGVH status, analyzing impact on overall survival (OS). Only 9% of NOTCH1 mut developed Richter syndrome with fatal outcome, confirming a worse prognostic role characterized by chemoresistance and rapid disease kinetics.
Conclusion
We choose to emphasize our real life data related to IGHV, FISH aberrations and NOTCH1 mut, not yet widely applied in everyday care, confirming the need for early identification of well-known biological and clinical findings. Interesting results related to IGHV and OS must be validated through large prospective cohort study, suggesting a clue for possible other biological factors and encouraging the introduction of innovative genetic lesion analysis (ie, NGS), with the aim of selecting high risk vs low risk patients.
Session topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical
Keyword(s): Chronic Lymphocytic Leukemia, FISH, IGH, Notch