The Experts below are selected from a list of 7257 Experts worldwide ranked by ideXlab platform
Xavier Badoux - One of the best experts on this subject based on the ideXlab platform.
-
high durable minimal residual disease negativity mrd with venetoclax rituximab venr in relapsed refractory r r cll mrd kinetics from phase 3 Murano study
Journal of Clinical Oncology, 2018Co-Authors: Peter Hillmen, John F. Seymour, Arnon P Kater, Anton W Langerak, Barbara Eichhorst, Carolyn Owen, Sarit Assouline, Ann Janssens, Paula Marlton, Xavier BadouxAbstract:7508Background: Survival with chemoimmunotherapy is associated with MRD–, but the importance of MRD with targeted agents and in R/R setting remains unclear, mostly due to low MRD– rates. In Murano,...
-
High, durable minimal residual disease negativity (MRD–) with venetoclax + rituximab (VenR) in relapsed/refractory (R/R) CLL: MRD kinetics from phase 3 Murano study.
Journal of Clinical Oncology, 2018Co-Authors: Peter Hillmen, John F. Seymour, Arnon P Kater, Anton W Langerak, Barbara Eichhorst, Carolyn Owen, Sarit Assouline, Ann Janssens, Paula Marlton, Xavier BadouxAbstract:7508Background: Survival with chemoimmunotherapy is associated with MRD–, but the importance of MRD with targeted agents and in R/R setting remains unclear, mostly due to low MRD– rates. In Murano,...
Rong Deng - One of the best experts on this subject based on the ideXlab platform.
-
exposure response analysis of venetoclax in combination with rituximab in patients with relapsed or refractory chronic lymphocytic leukemia pooled results from a phase 1b study and the phase 3 Murano study
Leukemia & Lymphoma, 2020Co-Authors: Rong Deng, Leonid Gibiansky, Tong Lu, Xiaobin Li, Dan Lu, Chunze Li, Sandhya Girish, Jue Wang, Michelle Boyer, Noopur ShankarAbstract:AbstractExposure–response relationships from a phase 1b (M13-365) and phase 3 (Murano) study were investigated to assess benefit/risk of venetoclax 400 mg daily plus rituximab in relapsed/refractor...
-
bayesian population model of the pharmacokinetics of venetoclax in combination with rituximab in patients with relapsed refractory chronic lymphocytic leukemia results from the phase iii Murano study
Clinical Pharmacokinectics, 2019Co-Authors: Rong Deng, Leonid Gibiansky, Tong Lu, Xiaobin Li, Dan Lu, Chunze Li, Priya Agarwal, Hao Ding, Smita Kshirsagar, Sandhya GirishAbstract:BACKGROUND: Venetoclax is a selective B-cell lymphoma-2 (BCL-2) inhibitor approved for use as monotherapy or with rituximab in patients with chronic lymphocytic leukemia (CLL). The objectives of the current analysis of observed data from adult patients randomized to venetoclax-rituximab in the phase III Murano study were to characterize venetoclax pharmacokinetics (PKs) using a Bayesian approach, evaluate whether a previously developed population PK model for venetoclax can describe the PKs of venetoclax when administered with rituximab, and to determine post hoc estimates of PK parameters for the exposure-response analysis. METHODS: Parameter estimates and uncertainty estimated by a population PK model were used as priors. Additional covariate effects (CLL risk status, geographic region, and 17p deletion [del(17p)] status) were added to the model. The updated model was used to describe venetoclax PKs after repeated dosing in combination with rituximab, and to determine post hoc estimates of PK parameters for exposure-response analysis. RESULTS: The PK analysis included 600 quantifiable venetoclax PK samples from 182 patients in the Murano study. Model evaluation using standard diagnostic plots, visual predictive checks, and normalized prediction distribution error plots indicated no model deficiencies. There was no significant relationship between venetoclax apparent clearance (CL/F) and bodyweight, age, sex, mild and moderate hepatic and renal impairment, or coadministration of weak cytochrome P450 3A inhibitors. The chromosomal abnormality del(17p) and CLL risk status had no apparent effect on the PKs of venetoclax. A minimal increase in venetoclax CL/F (approximately 7%) was observed after coadministration with rituximab. CL/F was 30% lower in patients from Central and Eastern Europe (n = 60) or Asia (n = 4) compared with other regions (95% confidence interval [CI] 21-39%). Apparent central volume of distribution was 30% lower (95% CI 22-38%) in females (n = 56) compared with males (n = 126). No clinically significant impact of region or sex was observed on key safety and efficacy outcomes. CONCLUSIONS: The Bayesian model successfully characterized venetoclax PKs over time and confirmed key covariates affecting PKs in the Murano study. The model was deemed appropriate for further use in simulations and for generating individual patient PK parameters for subsequent exposure-response evaluation.
-
Exposure–response analysis of venetoclax in combination with rituximab in patients with relapsed or refractory chronic lymphocytic leukemia: pooled results from a phase 1b study and the phase 3 Murano study
Leukemia & Lymphoma, 2019Co-Authors: Rong Deng, Leonid Gibiansky, Tong Lu, Xiaobin Li, Dan Lu, Chunze Li, Sandhya Girish, Jue Wang, Michelle Boyer, Noopur ShankarAbstract:AbstractExposure–response relationships from a phase 1b (M13-365) and phase 3 (Murano) study were investigated to assess benefit/risk of venetoclax 400 mg daily plus rituximab in relapsed/refractor...
-
Bayesian Population Model of the Pharmacokinetics of Venetoclax in Combination with Rituximab in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia: Results from the Phase III Murano Study
Clinical Pharmacokinectics, 2019Co-Authors: Rong Deng, Leonid Gibiansky, Tong Lu, Xiaobin Li, Dan Lu, Chunze Li, Priya Agarwal, Hao Ding, Smita Kshirsagar, Sandhya GirishAbstract:Background: Venetoclax is a selective B-cell lymphoma-2 (BCL-2) inhibitor approved for use as monotherapy or with rituximab in patients with chronic lymphocytic leukemia (CLL). The objectives of the current analysis of observed data from adult patients randomized to venetoclax–rituximab in the phase III Murano study were to characterize venetoclax pharmacokinetics (PKs) using a Bayesian approach, evaluate whether a previously developed population PK model for venetoclax can describe the PKs of venetoclax when administered with rituximab, and to determine post hoc estimates of PK parameters for the exposure–response analysis. Methods: Parameter estimates and uncertainty estimated by a population PK model were used as priors. Additional covariate effects (CLL risk status, geographic region, and 17p deletion [del(17p)] status) were added to the model. The updated model was used to describe venetoclax PKs after repeated dosing in combination with rituximab, and to determine post hoc estimates of PK parameters for exposure–response analysis. Results: The PK analysis included 600 quantifiable venetoclax PK samples from 182 patients in the Murano study. Model evaluation using standard diagnostic plots, visual predictive checks, and normalized prediction distribution error plots indicated no model deficiencies. There was no significant relationship between venetoclax apparent clearance (CL/F) and bodyweight, age, sex, mild and moderate hepatic and renal impairment, or coadministration of weak cytochrome P450 3A inhibitors. The chromosomal abnormality del(17p) and CLL risk status had no apparent effect on the PKs of venetoclax. A minimal increase in venetoclax CL/F (approximately 7%) was observed after coadministration with rituximab. CL/F was 30% lower in patients from Central and Eastern Europe (n = 60) or Asia (n = 4) compared with other regions (95% confidence interval [CI] 21–39%). Apparent central volume of distribution was 30% lower (95% CI 22–38%) in females (n = 56) compared with males (n = 126). No clinically significant impact of region or sex was observed on key safety and efficacy outcomes. Conclusions: The Bayesian model successfully characterized venetoclax PKs over time and confirmed key covariates affecting PKs in the Murano study. The model was deemed appropriate for further use in simulations and for generating individual patient PK parameters for subsequent exposure–response evaluation.
Sandhya Girish - One of the best experts on this subject based on the ideXlab platform.
-
exposure response analysis of venetoclax in combination with rituximab in patients with relapsed or refractory chronic lymphocytic leukemia pooled results from a phase 1b study and the phase 3 Murano study
Leukemia & Lymphoma, 2020Co-Authors: Rong Deng, Leonid Gibiansky, Tong Lu, Xiaobin Li, Dan Lu, Chunze Li, Sandhya Girish, Jue Wang, Michelle Boyer, Noopur ShankarAbstract:AbstractExposure–response relationships from a phase 1b (M13-365) and phase 3 (Murano) study were investigated to assess benefit/risk of venetoclax 400 mg daily plus rituximab in relapsed/refractor...
-
bayesian population model of the pharmacokinetics of venetoclax in combination with rituximab in patients with relapsed refractory chronic lymphocytic leukemia results from the phase iii Murano study
Clinical Pharmacokinectics, 2019Co-Authors: Rong Deng, Leonid Gibiansky, Tong Lu, Xiaobin Li, Dan Lu, Chunze Li, Priya Agarwal, Hao Ding, Smita Kshirsagar, Sandhya GirishAbstract:BACKGROUND: Venetoclax is a selective B-cell lymphoma-2 (BCL-2) inhibitor approved for use as monotherapy or with rituximab in patients with chronic lymphocytic leukemia (CLL). The objectives of the current analysis of observed data from adult patients randomized to venetoclax-rituximab in the phase III Murano study were to characterize venetoclax pharmacokinetics (PKs) using a Bayesian approach, evaluate whether a previously developed population PK model for venetoclax can describe the PKs of venetoclax when administered with rituximab, and to determine post hoc estimates of PK parameters for the exposure-response analysis. METHODS: Parameter estimates and uncertainty estimated by a population PK model were used as priors. Additional covariate effects (CLL risk status, geographic region, and 17p deletion [del(17p)] status) were added to the model. The updated model was used to describe venetoclax PKs after repeated dosing in combination with rituximab, and to determine post hoc estimates of PK parameters for exposure-response analysis. RESULTS: The PK analysis included 600 quantifiable venetoclax PK samples from 182 patients in the Murano study. Model evaluation using standard diagnostic plots, visual predictive checks, and normalized prediction distribution error plots indicated no model deficiencies. There was no significant relationship between venetoclax apparent clearance (CL/F) and bodyweight, age, sex, mild and moderate hepatic and renal impairment, or coadministration of weak cytochrome P450 3A inhibitors. The chromosomal abnormality del(17p) and CLL risk status had no apparent effect on the PKs of venetoclax. A minimal increase in venetoclax CL/F (approximately 7%) was observed after coadministration with rituximab. CL/F was 30% lower in patients from Central and Eastern Europe (n = 60) or Asia (n = 4) compared with other regions (95% confidence interval [CI] 21-39%). Apparent central volume of distribution was 30% lower (95% CI 22-38%) in females (n = 56) compared with males (n = 126). No clinically significant impact of region or sex was observed on key safety and efficacy outcomes. CONCLUSIONS: The Bayesian model successfully characterized venetoclax PKs over time and confirmed key covariates affecting PKs in the Murano study. The model was deemed appropriate for further use in simulations and for generating individual patient PK parameters for subsequent exposure-response evaluation.
-
Exposure–response analysis of venetoclax in combination with rituximab in patients with relapsed or refractory chronic lymphocytic leukemia: pooled results from a phase 1b study and the phase 3 Murano study
Leukemia & Lymphoma, 2019Co-Authors: Rong Deng, Leonid Gibiansky, Tong Lu, Xiaobin Li, Dan Lu, Chunze Li, Sandhya Girish, Jue Wang, Michelle Boyer, Noopur ShankarAbstract:AbstractExposure–response relationships from a phase 1b (M13-365) and phase 3 (Murano) study were investigated to assess benefit/risk of venetoclax 400 mg daily plus rituximab in relapsed/refractor...
-
Bayesian Population Model of the Pharmacokinetics of Venetoclax in Combination with Rituximab in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia: Results from the Phase III Murano Study
Clinical Pharmacokinectics, 2019Co-Authors: Rong Deng, Leonid Gibiansky, Tong Lu, Xiaobin Li, Dan Lu, Chunze Li, Priya Agarwal, Hao Ding, Smita Kshirsagar, Sandhya GirishAbstract:Background: Venetoclax is a selective B-cell lymphoma-2 (BCL-2) inhibitor approved for use as monotherapy or with rituximab in patients with chronic lymphocytic leukemia (CLL). The objectives of the current analysis of observed data from adult patients randomized to venetoclax–rituximab in the phase III Murano study were to characterize venetoclax pharmacokinetics (PKs) using a Bayesian approach, evaluate whether a previously developed population PK model for venetoclax can describe the PKs of venetoclax when administered with rituximab, and to determine post hoc estimates of PK parameters for the exposure–response analysis. Methods: Parameter estimates and uncertainty estimated by a population PK model were used as priors. Additional covariate effects (CLL risk status, geographic region, and 17p deletion [del(17p)] status) were added to the model. The updated model was used to describe venetoclax PKs after repeated dosing in combination with rituximab, and to determine post hoc estimates of PK parameters for exposure–response analysis. Results: The PK analysis included 600 quantifiable venetoclax PK samples from 182 patients in the Murano study. Model evaluation using standard diagnostic plots, visual predictive checks, and normalized prediction distribution error plots indicated no model deficiencies. There was no significant relationship between venetoclax apparent clearance (CL/F) and bodyweight, age, sex, mild and moderate hepatic and renal impairment, or coadministration of weak cytochrome P450 3A inhibitors. The chromosomal abnormality del(17p) and CLL risk status had no apparent effect on the PKs of venetoclax. A minimal increase in venetoclax CL/F (approximately 7%) was observed after coadministration with rituximab. CL/F was 30% lower in patients from Central and Eastern Europe (n = 60) or Asia (n = 4) compared with other regions (95% confidence interval [CI] 21–39%). Apparent central volume of distribution was 30% lower (95% CI 22–38%) in females (n = 56) compared with males (n = 126). No clinically significant impact of region or sex was observed on key safety and efficacy outcomes. Conclusions: The Bayesian model successfully characterized venetoclax PKs over time and confirmed key covariates affecting PKs in the Murano study. The model was deemed appropriate for further use in simulations and for generating individual patient PK parameters for subsequent exposure–response evaluation.
Noopur Shankar - One of the best experts on this subject based on the ideXlab platform.
-
exposure response analysis of venetoclax in combination with rituximab in patients with relapsed or refractory chronic lymphocytic leukemia pooled results from a phase 1b study and the phase 3 Murano study
Leukemia & Lymphoma, 2020Co-Authors: Rong Deng, Leonid Gibiansky, Tong Lu, Xiaobin Li, Dan Lu, Chunze Li, Sandhya Girish, Jue Wang, Michelle Boyer, Noopur ShankarAbstract:AbstractExposure–response relationships from a phase 1b (M13-365) and phase 3 (Murano) study were investigated to assess benefit/risk of venetoclax 400 mg daily plus rituximab in relapsed/refractor...
-
Exposure–response analysis of venetoclax in combination with rituximab in patients with relapsed or refractory chronic lymphocytic leukemia: pooled results from a phase 1b study and the phase 3 Murano study
Leukemia & Lymphoma, 2019Co-Authors: Rong Deng, Leonid Gibiansky, Tong Lu, Xiaobin Li, Dan Lu, Chunze Li, Sandhya Girish, Jue Wang, Michelle Boyer, Noopur ShankarAbstract:AbstractExposure–response relationships from a phase 1b (M13-365) and phase 3 (Murano) study were investigated to assess benefit/risk of venetoclax 400 mg daily plus rituximab in relapsed/refractor...
Michelle Boyer - One of the best experts on this subject based on the ideXlab platform.
-
exposure response analysis of venetoclax in combination with rituximab in patients with relapsed or refractory chronic lymphocytic leukemia pooled results from a phase 1b study and the phase 3 Murano study
Leukemia & Lymphoma, 2020Co-Authors: Rong Deng, Leonid Gibiansky, Tong Lu, Xiaobin Li, Dan Lu, Chunze Li, Sandhya Girish, Jue Wang, Michelle Boyer, Noopur ShankarAbstract:AbstractExposure–response relationships from a phase 1b (M13-365) and phase 3 (Murano) study were investigated to assess benefit/risk of venetoclax 400 mg daily plus rituximab in relapsed/refractor...
-
Exposure–response analysis of venetoclax in combination with rituximab in patients with relapsed or refractory chronic lymphocytic leukemia: pooled results from a phase 1b study and the phase 3 Murano study
Leukemia & Lymphoma, 2019Co-Authors: Rong Deng, Leonid Gibiansky, Tong Lu, Xiaobin Li, Dan Lu, Chunze Li, Sandhya Girish, Jue Wang, Michelle Boyer, Noopur ShankarAbstract:AbstractExposure–response relationships from a phase 1b (M13-365) and phase 3 (Murano) study were investigated to assess benefit/risk of venetoclax 400 mg daily plus rituximab in relapsed/refractor...
-
efficacy and safety of ibrutinib ibr after venetoclax ven treatment in ibr naive patients with relapsed refractory r r chronic lymphocytic leukemia cll follow up of patients from the Murano study
Blood, 2018Co-Authors: Richard Greil, Michelle Boyer, Graeme Fraser, Brian Leber, Reinhard Marks, Giulia Quaresmini, Jan Moritz Middeke, Gianpietro Semenzato, William Schary, Madlaina BreuleuxAbstract:Introduction: The management of CLL has been transformed in recent years by the introduction of a number of targeted agents including the BCL2 inhibitor VEN, and the Bruton9s tyrosine kinase inhibitor IBR. In the US and EU, VEN is currently approved for patients who have received at least 1 prior therapy, whereas IBR has wider indications that include front-line therapy as well as R/R CLL. The mechanisms of action of VEN and IBR are complementary (Bose et al. F1000Research 2017); this has led to studies of combination therapy in patients with CLL (Wierda et al. J Clin Oncol Suppl. 2018). In addition, the documented activity of VEN in patients with IBR R/R disease (Jones et al. J Clin Oncol Suppl. 2016), together with current approvals, has resulted in VEN being suggested as a reasonable treatment choice for patients who discontinue IBR (Byrd et al. J Clin Oncol Suppl. 2018). However, the clinical benefit of IBR in patients pretreated with VEN is less clear. We present a post-hoc series, obtained after follow-up of 8 patients with R/R CLL who received IBR after fixed-duration VEN+rituximab (R) therapy in the Murano randomized phase 3 study (NCT02005471) (Seymour et al. N Engl J Med 2018). Methods: In Murano, 389 patients with R/R CLL were enrolled and treated with 6 cycles of VEN+R followed by VEN monotherapy once-daily for up to 2 years, or 6 cycles of bendamustine (B)+R. Progression-free survival (PFS), the primary study endpoint, was based on investigator assessment. The present case series focuses on VEN+R patients from Murano who developed progressive disease (PD), and who subsequently received IBR. Eight patients in the VEN+R group with PD subsequently received IBR (Table 1). The number of lines of therapy prior to VEN+R ranged from 1 (n=7) to 4 (n=1; median 1). Prior to VEN+R therapy, 7 of the patients (87.5%) received fludarabine+cyclophosphamide+R (FCR); of these, 3 patients (42.8%) achieved a complete response (CR), 3 (42.8%) achieved a partial response (PR), and 1 patient (14.2%) had stable disease (SD). Of these 7 patients, 2 were considered refractory to FCR before VEN+R therapy. At baseline (before VEN+R), three of the patients (37.5%) had chromosome 17p-deletion, and two patients (25%) had baseline lymph nodes ≥5 cm- Four of the 8 patients had IBR dose interruption or modification due to neutropenia (n=2), clarithromycin treatment (n=1), or cutaneous nevus biopsy (n=1). Multiple skin abscesses were reported in 1 patient. One patient had atrial fibrillation, and 2 patients had arthralgia (1 had nearly resolved on follow-up), and there were no reports of major bleeding. Conclusions: In this series of patients with R/R CLL who received IBR following prior VEN+R in the Murano study, IBR showed clinical activity and acceptable tolerability, with no new safety signals. Our results suggest that the use of IBR after relapse following VEN+R is a reasonable option in patients with CLL. More data will be collected from Murano on patients progressing after VEN+R who are subsequently treated with IBR monotherapy. Disclosures Greil:Takeda: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding; Merck: Honoraria, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Janssen: Other: TRAVEL, ACCOMMODATIONS, EXPENSES; BMS: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding; MSD: Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding; Astra Zeneca: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding; Sandoz: Honoraria, Research Funding. Fraser:AbbVie: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Celgene: Membership on an entity9s Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding; Gilead: Honoraria. Leber:Novartis Canada: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Novartis Canada: Honoraria, Membership on an entity9s Board of Directors or advisory committees. Marks:BMS: Honoraria; Servier: Honoraria; Merck: Honoraria. Middeke:Roche: Membership on an entity9s Board of Directors or advisory committees; Janssen: Membership on an entity9s Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity9s Board of Directors or advisory committees. Schary:AbbVie: Employment. Boyer:F. Hoffmann-La Roche Ltd: Employment, Equity Ownership. Breuleux:Roche: Employment, Equity Ownership; Gilead: Equity Ownership; Basilea: Patents & Royalties; Novartis: Patents & Royalties. Crompton:Roche: Employment, Equity Ownership. Humphrey:F. Hoffmann-La Roche Ltd: Employment, Equity Ownership. Marlton:Pfizer: Membership on an entity9s Board of Directors or advisory committees; GlycoMimetics: Research Funding; Roche: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity9s Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Astellas: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Celgene: Membership on an entity9s Board of Directors or advisory committees.
-
Efficacy and Safety of Ibrutinib (IBR) after Venetoclax (VEN) Treatment in IBR-Naïve Patients with Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL): Follow-up of Patients from the Murano Study
Blood, 2018Co-Authors: Richard Greil, Michelle Boyer, Graeme Fraser, Brian Leber, Reinhard Marks, Giulia Quaresmini, Jan Moritz Middeke, Gianpietro Semenzato, William Schary, Madlaina BreuleuxAbstract:Introduction: The management of CLL has been transformed in recent years by the introduction of a number of targeted agents including the BCL2 inhibitor VEN, and the Bruton9s tyrosine kinase inhibitor IBR. In the US and EU, VEN is currently approved for patients who have received at least 1 prior therapy, whereas IBR has wider indications that include front-line therapy as well as R/R CLL. The mechanisms of action of VEN and IBR are complementary (Bose et al. F1000Research 2017); this has led to studies of combination therapy in patients with CLL (Wierda et al. J Clin Oncol Suppl. 2018). In addition, the documented activity of VEN in patients with IBR R/R disease (Jones et al. J Clin Oncol Suppl. 2016), together with current approvals, has resulted in VEN being suggested as a reasonable treatment choice for patients who discontinue IBR (Byrd et al. J Clin Oncol Suppl. 2018). However, the clinical benefit of IBR in patients pretreated with VEN is less clear. We present a post-hoc series, obtained after follow-up of 8 patients with R/R CLL who received IBR after fixed-duration VEN+rituximab (R) therapy in the Murano randomized phase 3 study (NCT02005471) (Seymour et al. N Engl J Med 2018). Methods: In Murano, 389 patients with R/R CLL were enrolled and treated with 6 cycles of VEN+R followed by VEN monotherapy once-daily for up to 2 years, or 6 cycles of bendamustine (B)+R. Progression-free survival (PFS), the primary study endpoint, was based on investigator assessment. The present case series focuses on VEN+R patients from Murano who developed progressive disease (PD), and who subsequently received IBR. Eight patients in the VEN+R group with PD subsequently received IBR (Table 1). The number of lines of therapy prior to VEN+R ranged from 1 (n=7) to 4 (n=1; median 1). Prior to VEN+R therapy, 7 of the patients (87.5%) received fludarabine+cyclophosphamide+R (FCR); of these, 3 patients (42.8%) achieved a complete response (CR), 3 (42.8%) achieved a partial response (PR), and 1 patient (14.2%) had stable disease (SD). Of these 7 patients, 2 were considered refractory to FCR before VEN+R therapy. At baseline (before VEN+R), three of the patients (37.5%) had chromosome 17p-deletion, and two patients (25%) had baseline lymph nodes ≥5 cm- Four of the 8 patients had IBR dose interruption or modification due to neutropenia (n=2), clarithromycin treatment (n=1), or cutaneous nevus biopsy (n=1). Multiple skin abscesses were reported in 1 patient. One patient had atrial fibrillation, and 2 patients had arthralgia (1 had nearly resolved on follow-up), and there were no reports of major bleeding. Conclusions: In this series of patients with R/R CLL who received IBR following prior VEN+R in the Murano study, IBR showed clinical activity and acceptable tolerability, with no new safety signals. Our results suggest that the use of IBR after relapse following VEN+R is a reasonable option in patients with CLL. More data will be collected from Murano on patients progressing after VEN+R who are subsequently treated with IBR monotherapy. Disclosures Greil:Takeda: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding; Merck: Honoraria, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Janssen: Other: TRAVEL, ACCOMMODATIONS, EXPENSES; BMS: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding; MSD: Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding; Astra Zeneca: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding; Sandoz: Honoraria, Research Funding. Fraser:AbbVie: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Celgene: Membership on an entity9s Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding; Gilead: Honoraria. Leber:Novartis Canada: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Novartis Canada: Honoraria, Membership on an entity9s Board of Directors or advisory committees. Marks:BMS: Honoraria; Servier: Honoraria; Merck: Honoraria. Middeke:Roche: Membership on an entity9s Board of Directors or advisory committees; Janssen: Membership on an entity9s Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity9s Board of Directors or advisory committees. Schary:AbbVie: Employment. Boyer:F. Hoffmann-La Roche Ltd: Employment, Equity Ownership. Breuleux:Roche: Employment, Equity Ownership; Gilead: Equity Ownership; Basilea: Patents & Royalties; Novartis: Patents & Royalties. Crompton:Roche: Employment, Equity Ownership. Humphrey:F. Hoffmann-La Roche Ltd: Employment, Equity Ownership. Marlton:Pfizer: Membership on an entity9s Board of Directors or advisory committees; GlycoMimetics: Research Funding; Roche: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity9s Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Astellas: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Celgene: Membership on an entity9s Board of Directors or advisory committees.
