VENETOCLAX IS ACTIVE IN CLL PATIENTS WHO HAVE RELAPSED AFTER OR ARE REFRACTORY TO IBRUTINIB OR IDELALISIB
Author(s): ,
Steven Coutre
Affiliations:
Stanford Cancer Center, Stanford University School of Medicine,Stanford,United States
,
William Wierda
Affiliations:
University of Texas MD Anderson Cancer Center,Houston,United States
,
Michael Choi
Affiliations:
UCSD Moores Cancer Center,San Diego,United States
,
Matthew S Davids
Affiliations:
Dana-Farber Cancer Institute,Boston,United States
,
Bruce D Cheson
Affiliations:
Georgetown University Hospital,Washington,United States
,
Richard R Furman
Affiliations:
Weill Cornell Medicine,New York,United States
,
Nicole Lamanna
Affiliations:
Columbia University Medical Center,New York,United States
,
Paul M Barr
Affiliations:
Wilmot Cancer Institute, University of Rochester Medical Center,Rochester,United States
,
Herbert Eradat
Affiliations:
University of California Los Angeles,Los Angeles,United States
,
Ahmad Halwani
Affiliations:
University of Utah Healthcare,Salt Lake City,United States
,
Leonard Heffner
Affiliations:
Emory University School of Medicine,Atlanta,United States
,
Brenda Chyla
Affiliations:
AbbVie, Inc.,North Chicago,United States
,
Ming Zhu
Affiliations:
AbbVie, Inc.,North Chicago,United States
,
Jalaja Potluri
Affiliations:
AbbVie, Inc.,North Chicago,United States
,
Maria Verdugo
Affiliations:
AbbVie, Inc.,North Chicago,United States
,
Rod Humerickhouse
Affiliations:
AbbVie, Inc.,North Chicago,United States
,
Anthony R Mato
Affiliations:
Center for CLL, University of Pennsylvania,Philadelphia,United States
Jeffrey Jones
Affiliations:
The Ohio State University,Columbus,United States
(Abstract release date: 05/19/16) EHA Library. Coutre S. 06/11/16; 133487; P599
Dr. Steven E Coutre
Dr. Steven E Coutre
Contributions
Abstract
Abstract: P599

Type: Poster Presentation

Presentation during EHA21: On Saturday, June 11, 2016 from 17:30 - 19:00

Location: Poster area (Hall H)

Background
Patients (pts) with chronic lymphocytic leukemia (CLL) who relapse after or become refractory (R/R) to BCR pathway inhibitors have poor outcomes. Venetoclax (VEN) is a selective, oral BCL-2 inhibitor with significant activity in R/R CLL.

Aims
Primary endpoints are ORR by iwCLL criteria [week (w) 8, 24, then every 12w] and safety.

Methods
In this ongoing Ph 2 study, pts with CLL R/R to ibrutinib (IBR, Arm A) or idelalisib (IDE, Arm B) receive VEN 20 mg daily followed by 5-week ramp up to 400 mg daily. 

Results
54 pts were enrolled (41 A, 13 B), including 25 refractory to IBR and 6 to IDE; 12 and 6 were intolerant with CLL progression after stopping IBR and IDE, respectively; 3 in each arm had both IBR and IDE. 54% had > 5 prior therapies, 83% had unmutated IGHV, 20% had ALC > 100 x 109, 35% had del(17p), and 24% had ≥1 node ≥10 cm. Median time on VEN was 31.9 w (0.6– 52.9) for Arm A and 23.7 w (5.4–52.9) for Arm B.  8 in Arm A discontinued VEN (4 PD; 1 each respiratory failure, multi-organ failure, death of unknown cause, consent withdrawal); 2 in Arm B (1 PD, 1 non-response).   Efficacy in 48 evaluable pts is shown in the Table. In the refractory subsets, 14/22 Arm A pts and 3/5 Arm B pts achieved response. 8/27 pts who reached w24 were MRD-negative (10-4) by flow cytometry in blood (all Arm A: 2 CR, 1 nPR, 4 PR, 1 SD).
Best response in evaluable* pts, n (%)Arm An=38Arm Bn=10
ORR23 (61)5 (50)
  CR3 (8)0
  PR/nPR19 (50) / 1 (3)5 (50) / 0
SD10 (26)4 (40)
PD1 (3)1 (10)
DC before assessment4 (11)0
*3 in each arm are not yet evaluable
 Safety was consistent with prior reports. AEs in >20% pts: neutropenia (48%), diarrhea (37%), nausea (35%), anemia (32%), fatigue (24%), hyperphosphatemia (20%). Grade 3/4 AEs >10%: neutropenia (39%), thrombocytopenia (22%), anemia (20%), leukopenia (13%), pneumonia (13%). SAEs in ≥2 pts: pneumonia (9%), febrile neutropenia (7%), increased potassium, multi-organ failure, septic shock (4% each).  2 pts had laboratory TLS without clinical sequelae.

Conclusion
In CLL pts R/R to IBR or IDE, VEN monotherapy showed promising activity, including MRD negativity at 24w, with acceptable safety. This is the first prospective study to demonstrate efficacy in this poor prognosis population. Follow-up will assess depth and duration of response.

Session topic: CLL - Efficacy and safety of new treatments 3
Abstract: P599

Type: Poster Presentation

Presentation during EHA21: On Saturday, June 11, 2016 from 17:30 - 19:00

Location: Poster area (Hall H)

Background
Patients (pts) with chronic lymphocytic leukemia (CLL) who relapse after or become refractory (R/R) to BCR pathway inhibitors have poor outcomes. Venetoclax (VEN) is a selective, oral BCL-2 inhibitor with significant activity in R/R CLL.

Aims
Primary endpoints are ORR by iwCLL criteria [week (w) 8, 24, then every 12w] and safety.

Methods
In this ongoing Ph 2 study, pts with CLL R/R to ibrutinib (IBR, Arm A) or idelalisib (IDE, Arm B) receive VEN 20 mg daily followed by 5-week ramp up to 400 mg daily. 

Results
54 pts were enrolled (41 A, 13 B), including 25 refractory to IBR and 6 to IDE; 12 and 6 were intolerant with CLL progression after stopping IBR and IDE, respectively; 3 in each arm had both IBR and IDE. 54% had > 5 prior therapies, 83% had unmutated IGHV, 20% had ALC > 100 x 109, 35% had del(17p), and 24% had ≥1 node ≥10 cm. Median time on VEN was 31.9 w (0.6– 52.9) for Arm A and 23.7 w (5.4–52.9) for Arm B.  8 in Arm A discontinued VEN (4 PD; 1 each respiratory failure, multi-organ failure, death of unknown cause, consent withdrawal); 2 in Arm B (1 PD, 1 non-response).   Efficacy in 48 evaluable pts is shown in the Table. In the refractory subsets, 14/22 Arm A pts and 3/5 Arm B pts achieved response. 8/27 pts who reached w24 were MRD-negative (10-4) by flow cytometry in blood (all Arm A: 2 CR, 1 nPR, 4 PR, 1 SD).
Best response in evaluable* pts, n (%)Arm An=38Arm Bn=10
ORR23 (61)5 (50)
  CR3 (8)0
  PR/nPR19 (50) / 1 (3)5 (50) / 0
SD10 (26)4 (40)
PD1 (3)1 (10)
DC before assessment4 (11)0
*3 in each arm are not yet evaluable
 Safety was consistent with prior reports. AEs in >20% pts: neutropenia (48%), diarrhea (37%), nausea (35%), anemia (32%), fatigue (24%), hyperphosphatemia (20%). Grade 3/4 AEs >10%: neutropenia (39%), thrombocytopenia (22%), anemia (20%), leukopenia (13%), pneumonia (13%). SAEs in ≥2 pts: pneumonia (9%), febrile neutropenia (7%), increased potassium, multi-organ failure, septic shock (4% each).  2 pts had laboratory TLS without clinical sequelae.

Conclusion
In CLL pts R/R to IBR or IDE, VEN monotherapy showed promising activity, including MRD negativity at 24w, with acceptable safety. This is the first prospective study to demonstrate efficacy in this poor prognosis population. Follow-up will assess depth and duration of response.

Session topic: CLL - Efficacy and safety of new treatments 3

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