FACTORS ASSOCIATED WITH TREATMENT CHOICE AND RESPONSE IN RELAPSED AND REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS RE-TREATED WITH RITUXIMAB: THE OBSERVATIONAL PERLE STUDY
(Abstract release date: 05/19/16)
EHA Library. Chaoui D. 06/09/16; 134697; PB1797
Ms. Driss Chaoui
Contributions
Contributions
Abstract
Abstract: PB1797
Type: Publication Only
Background
The treatment of patients with relapsed and refractory chronic lymphocytic leukemia (r/rCLL) previously treated with rituximab-based regimen (R) and re-treated with rituximab is relatively complex.
Aims
Exploratory analyses were conducted to identify factors leading to the choice of a specific combined chemoimmunotherapy: R-Bendamustine (RB), R-purine analogs (RP), R-alkylating agents (RA) or others regimens (Oth) and factors associated with the quality of response.
Methods
PERLE is a prospective non-interventional cohort study (main results presented at EHA 2014 - P876) conducted in r/rCLL patients. Two sets of exploratory analyses using data-mining methods were performed on baseline characteristics: decision trees to find patterns of factors defining subgroups of patients and random forests to provide a robust predictor model with a ranking between all available information. To confirm these outputs, standard logistic models, univariate and multivariate were implemented. Among baseline characteristics (clinical, demographics, disease and patients’ management) analysed with data mining, some were identified as candidate factors. The most impacting factors associated either with choice of chemotherapy or with response were confirmed by multivariate analyses.
Results
Overall, 310 patients were included. Their median age was 72 years [35 - 93] and 68% were men. The majority (187, 60%) was in first relapse. Rituximab was administered during first (69%), second (94%), or both (16%) previous treatment lines.More than half of the patients received RB, 16% received RP and 18% received RA (including 40% with chlorambucil). RB was favored in patients with a previous purine based-treatment (OR = 2.36 [1.4; 3.9]) which is the opposite of RP (OR = 0.39 [0.2; 0.8]). RA was preferentially prescribed in elderly patients (≥70 y.o., OR = 4.29 [2.0; 8.9]).Overall response rate (ORR) at the end of induction was 84%. A significantly better response was observed with the use of 500mg/m2 rituximab dose versus 375mg/m2 (84.5% versus 53.4%), when neutrophils count was ≥ 1.109/L versus < 1.109/L, (76.3% versus 47.4%) and when response duration was ≥ 12 months versus < 12 months (80.1% versus 62.5%). The number of previous rituximab-based treatment lines also impacts the quality of the response: ORR 76.2% with 1 treatment line versus ORR 45.0% with 2 previous treatment lines. Imbalance between responders and non-responders according to 17p deletion was also observed (patients with deletions: 49% responders; without deletion: 80%). Furthermore, ORR differences were observed between treatment groups: 85% with RB, 89% with RP, and 78% with RA.In this observational study, adverse events (all grades) were hematological (26.9%, including neutropenia (11.9%)) and infectious (14.4%). Grade ≥ 3AEs occurred in 28.4% of patients and were mainly hematological (19.7%); 22 patients (6.9%) died during induction treatment (15 deaths related to progression; 7 for AEs).
Conclusion
In real-life setting, treatment choice for r/r CLL is multifactorial. Overall, whatever the patient’s profile and the treatment strategy, the dose of rituximab (500mg/m²), as well as a single previous rituximab-based treatment line, are associated with a significantly better quality of response.
Session topic: E-poster
Keyword(s): Chronic lymphocytic leukemia, Retreatment, Rituximab
Type: Publication Only
Background
The treatment of patients with relapsed and refractory chronic lymphocytic leukemia (r/rCLL) previously treated with rituximab-based regimen (R) and re-treated with rituximab is relatively complex.
Aims
Exploratory analyses were conducted to identify factors leading to the choice of a specific combined chemoimmunotherapy: R-Bendamustine (RB), R-purine analogs (RP), R-alkylating agents (RA) or others regimens (Oth) and factors associated with the quality of response.
Methods
PERLE is a prospective non-interventional cohort study (main results presented at EHA 2014 - P876) conducted in r/rCLL patients. Two sets of exploratory analyses using data-mining methods were performed on baseline characteristics: decision trees to find patterns of factors defining subgroups of patients and random forests to provide a robust predictor model with a ranking between all available information. To confirm these outputs, standard logistic models, univariate and multivariate were implemented. Among baseline characteristics (clinical, demographics, disease and patients’ management) analysed with data mining, some were identified as candidate factors. The most impacting factors associated either with choice of chemotherapy or with response were confirmed by multivariate analyses.
Results
Overall, 310 patients were included. Their median age was 72 years [35 - 93] and 68% were men. The majority (187, 60%) was in first relapse. Rituximab was administered during first (69%), second (94%), or both (16%) previous treatment lines.More than half of the patients received RB, 16% received RP and 18% received RA (including 40% with chlorambucil). RB was favored in patients with a previous purine based-treatment (OR = 2.36 [1.4; 3.9]) which is the opposite of RP (OR = 0.39 [0.2; 0.8]). RA was preferentially prescribed in elderly patients (≥70 y.o., OR = 4.29 [2.0; 8.9]).Overall response rate (ORR) at the end of induction was 84%. A significantly better response was observed with the use of 500mg/m2 rituximab dose versus 375mg/m2 (84.5% versus 53.4%), when neutrophils count was ≥ 1.109/L versus < 1.109/L, (76.3% versus 47.4%) and when response duration was ≥ 12 months versus < 12 months (80.1% versus 62.5%). The number of previous rituximab-based treatment lines also impacts the quality of the response: ORR 76.2% with 1 treatment line versus ORR 45.0% with 2 previous treatment lines. Imbalance between responders and non-responders according to 17p deletion was also observed (patients with deletions: 49% responders; without deletion: 80%). Furthermore, ORR differences were observed between treatment groups: 85% with RB, 89% with RP, and 78% with RA.In this observational study, adverse events (all grades) were hematological (26.9%, including neutropenia (11.9%)) and infectious (14.4%). Grade ≥ 3AEs occurred in 28.4% of patients and were mainly hematological (19.7%); 22 patients (6.9%) died during induction treatment (15 deaths related to progression; 7 for AEs).
Conclusion
In real-life setting, treatment choice for r/r CLL is multifactorial. Overall, whatever the patient’s profile and the treatment strategy, the dose of rituximab (500mg/m²), as well as a single previous rituximab-based treatment line, are associated with a significantly better quality of response.
Session topic: E-poster
Keyword(s): Chronic lymphocytic leukemia, Retreatment, Rituximab
Abstract: PB1797
Type: Publication Only
Background
The treatment of patients with relapsed and refractory chronic lymphocytic leukemia (r/rCLL) previously treated with rituximab-based regimen (R) and re-treated with rituximab is relatively complex.
Aims
Exploratory analyses were conducted to identify factors leading to the choice of a specific combined chemoimmunotherapy: R-Bendamustine (RB), R-purine analogs (RP), R-alkylating agents (RA) or others regimens (Oth) and factors associated with the quality of response.
Methods
PERLE is a prospective non-interventional cohort study (main results presented at EHA 2014 - P876) conducted in r/rCLL patients. Two sets of exploratory analyses using data-mining methods were performed on baseline characteristics: decision trees to find patterns of factors defining subgroups of patients and random forests to provide a robust predictor model with a ranking between all available information. To confirm these outputs, standard logistic models, univariate and multivariate were implemented. Among baseline characteristics (clinical, demographics, disease and patients’ management) analysed with data mining, some were identified as candidate factors. The most impacting factors associated either with choice of chemotherapy or with response were confirmed by multivariate analyses.
Results
Overall, 310 patients were included. Their median age was 72 years [35 - 93] and 68% were men. The majority (187, 60%) was in first relapse. Rituximab was administered during first (69%), second (94%), or both (16%) previous treatment lines.More than half of the patients received RB, 16% received RP and 18% received RA (including 40% with chlorambucil). RB was favored in patients with a previous purine based-treatment (OR = 2.36 [1.4; 3.9]) which is the opposite of RP (OR = 0.39 [0.2; 0.8]). RA was preferentially prescribed in elderly patients (≥70 y.o., OR = 4.29 [2.0; 8.9]).Overall response rate (ORR) at the end of induction was 84%. A significantly better response was observed with the use of 500mg/m2 rituximab dose versus 375mg/m2 (84.5% versus 53.4%), when neutrophils count was ≥ 1.109/L versus < 1.109/L, (76.3% versus 47.4%) and when response duration was ≥ 12 months versus < 12 months (80.1% versus 62.5%). The number of previous rituximab-based treatment lines also impacts the quality of the response: ORR 76.2% with 1 treatment line versus ORR 45.0% with 2 previous treatment lines. Imbalance between responders and non-responders according to 17p deletion was also observed (patients with deletions: 49% responders; without deletion: 80%). Furthermore, ORR differences were observed between treatment groups: 85% with RB, 89% with RP, and 78% with RA.In this observational study, adverse events (all grades) were hematological (26.9%, including neutropenia (11.9%)) and infectious (14.4%). Grade ≥ 3AEs occurred in 28.4% of patients and were mainly hematological (19.7%); 22 patients (6.9%) died during induction treatment (15 deaths related to progression; 7 for AEs).
Conclusion
In real-life setting, treatment choice for r/r CLL is multifactorial. Overall, whatever the patient’s profile and the treatment strategy, the dose of rituximab (500mg/m²), as well as a single previous rituximab-based treatment line, are associated with a significantly better quality of response.
Session topic: E-poster
Keyword(s): Chronic lymphocytic leukemia, Retreatment, Rituximab
Type: Publication Only
Background
The treatment of patients with relapsed and refractory chronic lymphocytic leukemia (r/rCLL) previously treated with rituximab-based regimen (R) and re-treated with rituximab is relatively complex.
Aims
Exploratory analyses were conducted to identify factors leading to the choice of a specific combined chemoimmunotherapy: R-Bendamustine (RB), R-purine analogs (RP), R-alkylating agents (RA) or others regimens (Oth) and factors associated with the quality of response.
Methods
PERLE is a prospective non-interventional cohort study (main results presented at EHA 2014 - P876) conducted in r/rCLL patients. Two sets of exploratory analyses using data-mining methods were performed on baseline characteristics: decision trees to find patterns of factors defining subgroups of patients and random forests to provide a robust predictor model with a ranking between all available information. To confirm these outputs, standard logistic models, univariate and multivariate were implemented. Among baseline characteristics (clinical, demographics, disease and patients’ management) analysed with data mining, some were identified as candidate factors. The most impacting factors associated either with choice of chemotherapy or with response were confirmed by multivariate analyses.
Results
Overall, 310 patients were included. Their median age was 72 years [35 - 93] and 68% were men. The majority (187, 60%) was in first relapse. Rituximab was administered during first (69%), second (94%), or both (16%) previous treatment lines.More than half of the patients received RB, 16% received RP and 18% received RA (including 40% with chlorambucil). RB was favored in patients with a previous purine based-treatment (OR = 2.36 [1.4; 3.9]) which is the opposite of RP (OR = 0.39 [0.2; 0.8]). RA was preferentially prescribed in elderly patients (≥70 y.o., OR = 4.29 [2.0; 8.9]).Overall response rate (ORR) at the end of induction was 84%. A significantly better response was observed with the use of 500mg/m2 rituximab dose versus 375mg/m2 (84.5% versus 53.4%), when neutrophils count was ≥ 1.109/L versus < 1.109/L, (76.3% versus 47.4%) and when response duration was ≥ 12 months versus < 12 months (80.1% versus 62.5%). The number of previous rituximab-based treatment lines also impacts the quality of the response: ORR 76.2% with 1 treatment line versus ORR 45.0% with 2 previous treatment lines. Imbalance between responders and non-responders according to 17p deletion was also observed (patients with deletions: 49% responders; without deletion: 80%). Furthermore, ORR differences were observed between treatment groups: 85% with RB, 89% with RP, and 78% with RA.In this observational study, adverse events (all grades) were hematological (26.9%, including neutropenia (11.9%)) and infectious (14.4%). Grade ≥ 3AEs occurred in 28.4% of patients and were mainly hematological (19.7%); 22 patients (6.9%) died during induction treatment (15 deaths related to progression; 7 for AEs).
Conclusion
In real-life setting, treatment choice for r/r CLL is multifactorial. Overall, whatever the patient’s profile and the treatment strategy, the dose of rituximab (500mg/m²), as well as a single previous rituximab-based treatment line, are associated with a significantly better quality of response.
Session topic: E-poster
Keyword(s): Chronic lymphocytic leukemia, Retreatment, Rituximab
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