RAPID DOSE ESCALATION OF VENETOCLAX IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA PREVIOUSLY TREATED WITH B-CELL RECEPTOR INHIBITOR THERAPY
Author(s): ,
Kristin Koenig
Affiliations:
Department of Internal Medicine,The Ohio State University Wexner Medical Center,Columbus,United States
,
Daniel Konstantinou
Affiliations:
The Ohio State University College of Medicine,Columbus,United States
,
Andrew Rogers
Affiliations:
Division of Hematology,The James Cancer Hospital and Solove Research Institute at The Ohio State University,Columbus,United States
,
Tracy Wiczer
Affiliations:
Department of Pharmacy,The James Cancer Hospital and Solove Research Institute at The Ohio State University,Columbus,United States
,
Kerry Rogers
Affiliations:
Division of Hematology,The James Cancer Hospital and Solove Research Institute at The Ohio State University,Columbus,United States
,
Jennifer Woyach
Affiliations:
Division of Hematology,The James Cancer Hospital and Solove Research Institute at The Ohio State University,Columbus,United States
,
John Byrd
Affiliations:
Division of Hematology,The James Cancer Hospital and Solove Research Institute at The Ohio State University,Columbus,United States
Farrukh Awan
Affiliations:
Division of Hematology,The James Cancer Hospital and Solove Research Institute at The Ohio State University,Columbus,United States
EHA Library. Koenig K. 06/15/18; 214830; PF357
Kristin Koenig
Kristin Koenig
Contributions
Abstract

Abstract: PF357

Type: Poster Presentation

Presentation during EHA23: On Friday, June 15, 2018 from 17:30 - 19:00

Location: Poster area

Background

Despite the remarkable disease control observed with B-cell receptor pathway inhibitors (BCRi), patients with chronic lymphocytic leukemia (CLL) who relapse after these agents frequently tend to have rapidly progressive, symptomatic disease that requires immediate intervention and disease control.1 Venetoclax selectively inhibits anti-apoptotic protein B-cell lymphoma 2 (BCL-2), and is the only agent that has demonstrated remarkable efficacy after BCRi therapy.2,3 However, its use requires a slow, weekly dosing ramp-up from 20mg to 400mg goal dose over 5 weeks, to reduce the risk of tumor lysis syndrome (TLS).3 Herein, we report our experience with a rapid dose escalation protocol for venetoclax that attains prompt disease control.

Aims

Given the need to promptly attain goal venetoclax dose, we aim to demonstrate the feasibility, safety/tolerability, and efficacy of a “rapid dose escalation” of venetoclax in relapsed/refractory CLL pts previously treated with BCRi in a properly equipped university institution.

Methods

With permission from an IRB approved protocol, data was retrospectively compiled from medical records of patients who received rapid venetoclax (dosing ramp up < 5 weeks to goal dose). Patient demographics, treatment, disease, and survival outcomes were collected. Detailed safety and efficacy measures were also assessed.

Results

Fifteen patients received rapid venetoclax dose escalation as inpatients with close laboratory and clinical monitoring and aggressive supportive care for laboratory and clinical TLS. Median age was 65 years (range 48-77) and 80% were men with ECOG 0-1 in 93% of patients. Patients had received a median of 5 previous treatments (range 3-7). Most recent prior treatment was a BCRi alone in 10 patients, BCRi in combination with chemotherapy in 3 and high dose steroids in 2 patients. The BCRi treatments overlapped with venetoclax in 6 patients. High risk cytogenetics were present in the majority of patients including: complex karyotype in 60%, del17p in 67% and unmutated IGHV in 80%. Three patients had high tumor burden disease (per venetolax package insert and NCCN Guidelines) and 73% had confirmed BTK/PLCG2 mutations. The mean time to goal venetoclax dose was 12 days (range 5-21), and all patients reached goal dose. Seven (46.7%) pts developed tumor lysis syndrome (TLS) by lab criteria at doses ranging from 20-200 mg (1 patient at 20 mg, 2 patients each at the 50 mg, 100 mg and 200 mg dose); but only 2 patients developed TLS by clinical criteria, of grade 0 or 1 severity (per Cairo-Bishop definition). No patients required renal replacement; 53.3% had an elevated uric acid requiring rasburicase and 40% had hyperphosphatemia requiring phosphate binders. Twelve patients (80%) achieved a partial response, 2 had progressive disease and 1 patient died within 30 days from progressive disease. Mean time to best response was 71 days (range 13-428), and to subsequent treatment was 298 days (range 204-430).

Conclusion

Rapid dose escalation of venetoclax with close inpatient monitoring in experienced centers could be a feasible approach in patients with disease relapse after BCRi in patients who require urgent disease control. Further trials in these patients utilizing a consistent rapid dose escalation protocol are warranted.

Session topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical

Keyword(s): BCL2, Chronic Lymphocytic Leukemia, Relapse, Treatment

Abstract: PF357

Type: Poster Presentation

Presentation during EHA23: On Friday, June 15, 2018 from 17:30 - 19:00

Location: Poster area

Background

Despite the remarkable disease control observed with B-cell receptor pathway inhibitors (BCRi), patients with chronic lymphocytic leukemia (CLL) who relapse after these agents frequently tend to have rapidly progressive, symptomatic disease that requires immediate intervention and disease control.1 Venetoclax selectively inhibits anti-apoptotic protein B-cell lymphoma 2 (BCL-2), and is the only agent that has demonstrated remarkable efficacy after BCRi therapy.2,3 However, its use requires a slow, weekly dosing ramp-up from 20mg to 400mg goal dose over 5 weeks, to reduce the risk of tumor lysis syndrome (TLS).3 Herein, we report our experience with a rapid dose escalation protocol for venetoclax that attains prompt disease control.

Aims

Given the need to promptly attain goal venetoclax dose, we aim to demonstrate the feasibility, safety/tolerability, and efficacy of a “rapid dose escalation” of venetoclax in relapsed/refractory CLL pts previously treated with BCRi in a properly equipped university institution.

Methods

With permission from an IRB approved protocol, data was retrospectively compiled from medical records of patients who received rapid venetoclax (dosing ramp up < 5 weeks to goal dose). Patient demographics, treatment, disease, and survival outcomes were collected. Detailed safety and efficacy measures were also assessed.

Results

Fifteen patients received rapid venetoclax dose escalation as inpatients with close laboratory and clinical monitoring and aggressive supportive care for laboratory and clinical TLS. Median age was 65 years (range 48-77) and 80% were men with ECOG 0-1 in 93% of patients. Patients had received a median of 5 previous treatments (range 3-7). Most recent prior treatment was a BCRi alone in 10 patients, BCRi in combination with chemotherapy in 3 and high dose steroids in 2 patients. The BCRi treatments overlapped with venetoclax in 6 patients. High risk cytogenetics were present in the majority of patients including: complex karyotype in 60%, del17p in 67% and unmutated IGHV in 80%. Three patients had high tumor burden disease (per venetolax package insert and NCCN Guidelines) and 73% had confirmed BTK/PLCG2 mutations. The mean time to goal venetoclax dose was 12 days (range 5-21), and all patients reached goal dose. Seven (46.7%) pts developed tumor lysis syndrome (TLS) by lab criteria at doses ranging from 20-200 mg (1 patient at 20 mg, 2 patients each at the 50 mg, 100 mg and 200 mg dose); but only 2 patients developed TLS by clinical criteria, of grade 0 or 1 severity (per Cairo-Bishop definition). No patients required renal replacement; 53.3% had an elevated uric acid requiring rasburicase and 40% had hyperphosphatemia requiring phosphate binders. Twelve patients (80%) achieved a partial response, 2 had progressive disease and 1 patient died within 30 days from progressive disease. Mean time to best response was 71 days (range 13-428), and to subsequent treatment was 298 days (range 204-430).

Conclusion

Rapid dose escalation of venetoclax with close inpatient monitoring in experienced centers could be a feasible approach in patients with disease relapse after BCRi in patients who require urgent disease control. Further trials in these patients utilizing a consistent rapid dose escalation protocol are warranted.

Session topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical

Keyword(s): BCL2, Chronic Lymphocytic Leukemia, Relapse, Treatment

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