REGISTRY FOR THE OFF-LABEL USE OF VENETOCLAX IN PATIENTS WITH RELAPSED OR REFRACTORY ACUTE MYELOID LEUKEMIA
Author(s): ,
Rabia Shahswar
Affiliations:
Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation,Medical School Hannover,Hannover,Germany
,
Iyas Hamwi
Affiliations:
Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation,Medical School Hannover,Hannover,Germany
,
Catherina Lueck
Affiliations:
Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation,Medical School Hannover,Hannover,Germany
,
Michael Toepperwien
Affiliations:
Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation,Medical School Hannover,Hannover,Germany
,
Christian Koenecke
Affiliations:
Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation,Medical School Hannover,Hannover,Germany
,
Walter Fiedler
Affiliations:
Department of Medicine II, Oncological Center,Hubertus Wald University Cancer Center, University Hospital Hamburg-Eppendorf,Hamburg,Germany
,
Ramin Madanchi
Affiliations:
Department of Medicine II, Oncological Center,Hubertus Wald University Cancer Center, University Hospital Hamburg-Eppendorf,Hamburg,Germany
,
Juergen Krauter
Affiliations:
Department of Hematology and Oncology,Klinikum Braunschweig,Braunschweig,Germany
,
Arne Trummer
Affiliations:
Department of Hematology and Oncology,Klinikum Braunschweig,Braunschweig,Germany
,
Matthias Eder
Affiliations:
Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation,Medical School Hannover,Hannover,Germany
,
Gernot Beutel
Affiliations:
Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation,Medical School Hannover,Hannover,Germany
,
Michael Stadler
Affiliations:
Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation,Medical School Hannover,Hannover,Germany
,
Steve Ehrlich
Affiliations:
Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation,Medical School Hannover,Hannover,Germany
,
Lothar Hambach
Affiliations:
Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation,Medical School Hannover,Hannover,Germany
,
Arnold Ganser
Affiliations:
Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation,Medical School Hannover,Hannover,Germany
,
Felicitas Thol
Affiliations:
Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation,Medical School Hannover,Hannover,Germany
Michael Heuser
Affiliations:
Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation,Medical School Hannover,Hannover,Germany
(Abstract release date: 05/17/18) EHA Library. Shahswar R. 06/14/18; 216245; PB1735
Dr. Rabia Shahswar
Dr. Rabia Shahswar
Contributions
Abstract

Abstract: PB1735

Type: Publication Only

Background
Previous data have shown promising safety and efficacy of venetoclax (VEN) in combination with hypomethylating agents (HMAs) or low-dose cytarabine (LDAC) in untreated AML patients (pts). VEN is a potent oral small molecule inhibitor of the anti-apoptotic protein BCL-2 and is currently approved for use in refractory chronic lymphoid leukemia pts.

Aims
To establish a registry of AML patients treated with VEN off-label and to report initial results.

Methods
Patients with refractory or relapsed (R/R) AML who were treated with VEN at three German medical centers were included. Patients received VEN for salvage treatment in combination with HMAs or LDAC outside of a clinical trial. We retrospectively collected data regarding clinical, genetic and treatment characteristics. All patients had given informed consent to the off-label use of VEN, genetic analysis and use of clinical data according to the Declaration of Helsinki.

Results

Eight patients with R/R AML who received salvage treatment with VEN in combination with HMAs or LDAC were eligible for analysis. Median age was 68 years (range 41-78). The patient cohort had an unfavorable risk with 5 pts (63%) having secondary or therapy-related AML, 7 (88%) pts being treated in second or higher salvage therapy (range 1-4), 3 (38%) pts having adverse ELN risk, 7 (88%) pts having received prior HMA or LDAC therapy and 1 (12%) patient having received prior allogeneic stem cell transplantation (SCT). In 6 of 8 pts (75%) VEN was combined with azacitidine (n=5) or decitabine (n=1), in 2 pts (25%) it was combined with LDAC. The VEN dose ranged from 50 to 600 mg per day with dose reduction related to concomitant CYP3A4 inhibitor treatment, primarily azole antifungals, in 6 pts (75%). At data cutoff pts received a median of 2.5 cycles (range 1-7, one patient ongoing). Of the 7 patients who discontinued VEN, reasons included progressive disease (n=3), death in aplasia due to sepsis (n=1) and transition to SCT (n=3). The overall response rate (ORR), defined as complete response (CR) or CR with incomplete blood count recovery (CRi) or partial response (PR) per IWG criteria was 6/8 (75%, 1 CR, 3 CRi, 2 PR with peripheral blood count recovery). All 6 patients treated with dose-reduced VEN because of concomitant azole use achieved a response. Three pts were successfully bridged to transplant. Median follow up was 9.4 months. Median survival was 6.6 months. Five patients died (63%), 3 from progressive disease and 2 from infectious complications. Transfusion-dependent anemia (n=8) and thrombocytopenia (n=6) were common prior to the start of therapy. Four of 8 patients (50%) achieved red blood cell transfusion independence. Three of 6 patients (50%) achieved platelet transfusion independence with recovery of platelet counts to >50/nl after a median of 36 days (range 29-47). One pancytopenic patient only received VEN on days 1-14 of each cycle in combination with LDAC and achieved complete blood count recovery after the second cycle (PR).

Conclusion
We established a clinical registry for R/R AML patients who were treated with VEN. Results are comparable to other reports of off-label use in R/R AML patients. Efficacy of VEN was maintained after dose reduction for concomitant azole treatment. Continuous VEN dosing may result in long lasting cytopenias, which may require dose interruptions. Including patients treated with off-label VEN in a registry can help us to better understand this novel treatment.

Session topic: 4. Acute myeloid leukemia - Clinical

Keyword(s): BCL2, Relapsed acute myeloid leukemia, Salvage therapy

Abstract: PB1735

Type: Publication Only

Background
Previous data have shown promising safety and efficacy of venetoclax (VEN) in combination with hypomethylating agents (HMAs) or low-dose cytarabine (LDAC) in untreated AML patients (pts). VEN is a potent oral small molecule inhibitor of the anti-apoptotic protein BCL-2 and is currently approved for use in refractory chronic lymphoid leukemia pts.

Aims
To establish a registry of AML patients treated with VEN off-label and to report initial results.

Methods
Patients with refractory or relapsed (R/R) AML who were treated with VEN at three German medical centers were included. Patients received VEN for salvage treatment in combination with HMAs or LDAC outside of a clinical trial. We retrospectively collected data regarding clinical, genetic and treatment characteristics. All patients had given informed consent to the off-label use of VEN, genetic analysis and use of clinical data according to the Declaration of Helsinki.

Results

Eight patients with R/R AML who received salvage treatment with VEN in combination with HMAs or LDAC were eligible for analysis. Median age was 68 years (range 41-78). The patient cohort had an unfavorable risk with 5 pts (63%) having secondary or therapy-related AML, 7 (88%) pts being treated in second or higher salvage therapy (range 1-4), 3 (38%) pts having adverse ELN risk, 7 (88%) pts having received prior HMA or LDAC therapy and 1 (12%) patient having received prior allogeneic stem cell transplantation (SCT). In 6 of 8 pts (75%) VEN was combined with azacitidine (n=5) or decitabine (n=1), in 2 pts (25%) it was combined with LDAC. The VEN dose ranged from 50 to 600 mg per day with dose reduction related to concomitant CYP3A4 inhibitor treatment, primarily azole antifungals, in 6 pts (75%). At data cutoff pts received a median of 2.5 cycles (range 1-7, one patient ongoing). Of the 7 patients who discontinued VEN, reasons included progressive disease (n=3), death in aplasia due to sepsis (n=1) and transition to SCT (n=3). The overall response rate (ORR), defined as complete response (CR) or CR with incomplete blood count recovery (CRi) or partial response (PR) per IWG criteria was 6/8 (75%, 1 CR, 3 CRi, 2 PR with peripheral blood count recovery). All 6 patients treated with dose-reduced VEN because of concomitant azole use achieved a response. Three pts were successfully bridged to transplant. Median follow up was 9.4 months. Median survival was 6.6 months. Five patients died (63%), 3 from progressive disease and 2 from infectious complications. Transfusion-dependent anemia (n=8) and thrombocytopenia (n=6) were common prior to the start of therapy. Four of 8 patients (50%) achieved red blood cell transfusion independence. Three of 6 patients (50%) achieved platelet transfusion independence with recovery of platelet counts to >50/nl after a median of 36 days (range 29-47). One pancytopenic patient only received VEN on days 1-14 of each cycle in combination with LDAC and achieved complete blood count recovery after the second cycle (PR).

Conclusion
We established a clinical registry for R/R AML patients who were treated with VEN. Results are comparable to other reports of off-label use in R/R AML patients. Efficacy of VEN was maintained after dose reduction for concomitant azole treatment. Continuous VEN dosing may result in long lasting cytopenias, which may require dose interruptions. Including patients treated with off-label VEN in a registry can help us to better understand this novel treatment.

Session topic: 4. Acute myeloid leukemia - Clinical

Keyword(s): BCL2, Relapsed acute myeloid leukemia, Salvage therapy

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