PRELIMINARY SAFETY DATA FROM THE PHASE 3B GREEN STUDY OF OBINUTUZUMAB (G) ALONE OR COMBINED WITH CHEMOTHERAPY FOR PREVIOUSLY UNTREATED OR RELAPSED/REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)
Author(s): ,
Véronique Leblond
Affiliations:
AP-HP Hôpital Pitié-Salpêtrière, UPMC,Paris,France
,
Marie-Sarah Dilhuydy
Affiliations:
Hôpital du Haut-Lévèque, Centre Hospitalier Universitaire de Bordeaux,Bordeaux,France
,
Robin Foà
Affiliations:
‘Sapienza’ University,Rome,Italy
,
Wolfgang Knauf
Affiliations:
Onkologische Gemeinshaftspraxis,Frankfurt,Germany
,
Marco Montillo
Affiliations:
Niguarda Ca' Granda Hospital, Niguarda Cancer Center,Milan,Italy
,
Sue Robinson
Affiliations:
QEII Health Sciences Centre,Halifax,Canada
,
Stephan Stilgenbauer
Affiliations:
University of Ulm,Ulm,Germany
,
Ekaterina Gresko
Affiliations:
F. Hoffmann-La Roche Ltd,Basel,Switzerland
,
Susan Lasserre
Affiliations:
F. Hoffmann-La Roche Ltd,Basel,Switzerland
Francesc Bosch
Affiliations:
University Hospital Vall d’Hebron,Barcelona,Spain
(Abstract release date: 05/19/16) EHA Library. Leblond V. 06/11/16; 135183; S427
Dr. Véronique Leblond
Dr. Véronique Leblond
Contributions
Abstract
Abstract: S427

Type: Oral Presentation

Presentation during EHA21: On Saturday, June 11, 2016 from 11:30 - 11:45

Location: Hall A1

Background
GREEN (NCT01905943) is an ongoing phase 3b, open-label trial of G alone or with chemotherapy in pts with previously untreated (1L) or relapsed/refractory (R/R) CLL; the primary outcome is safety.

Aims
To assess the frequency, type and severity of AEs in all pts in GREEN, based on a 6-month safety review (data cut-off for analysis, 26 August 2015).

Methods
Enrolled pts are aged ≥18 yrs with documented CLL, ECOG PS 0-2 and adequate hematologic function. Pts receive G 1000mg IV, alone or with chemotherapy (at investigator’s discretion), on days 1 (dose split over 2 days [25+975mg or 100+900mg]), 8 and 15 of cycle (C)1, and day 1 of C2-6 (six 28-day cycles). Chemotherapy options were: fludarabine and cyclophosphamide (FC) for fit pts only (CIRS ≤6 and CrCl ≥70mL/min); chlorambucil (Clb) for unfit pts only (CIRS >6 and/or CrCl <70mL/min), or bendamustine (B) for any pt. Pts refractory to previous G monotherapy had to receive G with chemotherapy. All pts gave informed consent.

Results
In 825 pts analyzed (1L, 485; R/R, 340), median age was 66.0 (33-90) yrs, 63.4% were male, 434 (52.6%) were at risk of tumor lysis syndrome (TLS; tumor burden ≥10cm or ≥5cm but <10cm with lymphocytes ≥25x109/L) and 41.1%/33.5% were Binet stage B/C. Median observation time was 12.7 (0.1-22.1) months and median exposure time was 20.3 (0.1-33.1) weeks. AEs, grade ≥3 AEs and SAEs occurred in 96.1%, 72.0% and 43.1% of 1L pts, and 96.5%, 73.8% and 46.5% of R/R pts, respectively (results by treatment group in Table). The most common grade ≥3 AEs were neutropenia (44.7%), thrombocytopenia (TCP; 15.9%), anemia (9.0%), febrile neutropenia (6.9%), and leukopenia (6.2%). AEs were considered related to G treatment in 83.0% pts, most commonly neutropenia (36.0%), TCP (23.0%), pyrexia (21.7%), nausea (17.5%), chills (15.3%) and anemia (10.4%). AEs of particular interest (any grade) were: cardiac events, 8.7%; hemorrhagic events, 6.2%; TCP, 32.4%; and secondary malignancies, 4.1%. Other AEs of interest (any grade) were: infusion-related reactions (IRRs, ie. events occurring during or within 24h of G infusion and treatment-related), 63.3% (most common: pyrexia, 17.7%; chills, 14.8%; nausea, 12.5%; causing G discontinuation, 2.8%); infections, 45.2% (most common: pneumonia, 7.0%; bronchitis, 5.0%; URTI, 5.0%); neutropenia, 58.4% and TLS, 6.2%. In the G-B arm, TLS was more common in unfit pts (23; 10.0%) than fit pts (12; 5.2%). AEs caused G discontinuation in 111 (13.5%) pts. In 43 pts who died (1L fit, 9 [3.4%]; 1L unfit, 10 [4.5%]; R/R, 24 [7.1%]), primary causes were AEs (n=32) and disease progression (n=11); 15 were related to underlying cancer. One pt in the G-B arm (1L unfit) died of TLS before data cut-off.
N (%)Total (n=825)G alone (n=106)G-FC (n=159)G-Clb (n=97)G-B (n=463)
Any AE794 (96.2)98 (92.5)157 (98.7)97 (100)442 (95.5)
TLS51 (6.2)6 (5.7)7 (4.4)3 (3.1)35 (7.6)
Grade ≥3 AEs600 (72.7)66 (62.3)133 (83.6)63 (64.9)338 (73.0)
     Neutropenia369 (44.7)26 (24.5)93 (58.5)41 (42.3)209 (45.1)
     TCP131 (15.9)11 (10.4)34 (21.4)19 (19.6)67 (14.5)
Grade ≥3 infections123 (14.9)17 (16.0)17 (10.7)16 (16.5)73 (15.8)
Grade ≥3 IRRs152 (18.4)25 (23.6)33 (20.8)19 (19.6)75 (16.2)
Any SAE367 (44.5)44 (41.5)61 (38.4)39 (40.2)223 (48.2)
Any fatal AE32 (3.9%)4 (3.8%)4 (2.5%)3 (3.1%)21 (4.5%)


Conclusion
Preliminary safety data from GREEN are in line with the known safety profile of G in similar populations.

Session topic: Innovative therapies in CLL

Keyword(s): Chronic lymphocytic leukemia, Obinutuzumab, Safety
Abstract: S427

Type: Oral Presentation

Presentation during EHA21: On Saturday, June 11, 2016 from 11:30 - 11:45

Location: Hall A1

Background
GREEN (NCT01905943) is an ongoing phase 3b, open-label trial of G alone or with chemotherapy in pts with previously untreated (1L) or relapsed/refractory (R/R) CLL; the primary outcome is safety.

Aims
To assess the frequency, type and severity of AEs in all pts in GREEN, based on a 6-month safety review (data cut-off for analysis, 26 August 2015).

Methods
Enrolled pts are aged ≥18 yrs with documented CLL, ECOG PS 0-2 and adequate hematologic function. Pts receive G 1000mg IV, alone or with chemotherapy (at investigator’s discretion), on days 1 (dose split over 2 days [25+975mg or 100+900mg]), 8 and 15 of cycle (C)1, and day 1 of C2-6 (six 28-day cycles). Chemotherapy options were: fludarabine and cyclophosphamide (FC) for fit pts only (CIRS ≤6 and CrCl ≥70mL/min); chlorambucil (Clb) for unfit pts only (CIRS >6 and/or CrCl <70mL/min), or bendamustine (B) for any pt. Pts refractory to previous G monotherapy had to receive G with chemotherapy. All pts gave informed consent.

Results
In 825 pts analyzed (1L, 485; R/R, 340), median age was 66.0 (33-90) yrs, 63.4% were male, 434 (52.6%) were at risk of tumor lysis syndrome (TLS; tumor burden ≥10cm or ≥5cm but <10cm with lymphocytes ≥25x109/L) and 41.1%/33.5% were Binet stage B/C. Median observation time was 12.7 (0.1-22.1) months and median exposure time was 20.3 (0.1-33.1) weeks. AEs, grade ≥3 AEs and SAEs occurred in 96.1%, 72.0% and 43.1% of 1L pts, and 96.5%, 73.8% and 46.5% of R/R pts, respectively (results by treatment group in Table). The most common grade ≥3 AEs were neutropenia (44.7%), thrombocytopenia (TCP; 15.9%), anemia (9.0%), febrile neutropenia (6.9%), and leukopenia (6.2%). AEs were considered related to G treatment in 83.0% pts, most commonly neutropenia (36.0%), TCP (23.0%), pyrexia (21.7%), nausea (17.5%), chills (15.3%) and anemia (10.4%). AEs of particular interest (any grade) were: cardiac events, 8.7%; hemorrhagic events, 6.2%; TCP, 32.4%; and secondary malignancies, 4.1%. Other AEs of interest (any grade) were: infusion-related reactions (IRRs, ie. events occurring during or within 24h of G infusion and treatment-related), 63.3% (most common: pyrexia, 17.7%; chills, 14.8%; nausea, 12.5%; causing G discontinuation, 2.8%); infections, 45.2% (most common: pneumonia, 7.0%; bronchitis, 5.0%; URTI, 5.0%); neutropenia, 58.4% and TLS, 6.2%. In the G-B arm, TLS was more common in unfit pts (23; 10.0%) than fit pts (12; 5.2%). AEs caused G discontinuation in 111 (13.5%) pts. In 43 pts who died (1L fit, 9 [3.4%]; 1L unfit, 10 [4.5%]; R/R, 24 [7.1%]), primary causes were AEs (n=32) and disease progression (n=11); 15 were related to underlying cancer. One pt in the G-B arm (1L unfit) died of TLS before data cut-off.
N (%)Total (n=825)G alone (n=106)G-FC (n=159)G-Clb (n=97)G-B (n=463)
Any AE794 (96.2)98 (92.5)157 (98.7)97 (100)442 (95.5)
TLS51 (6.2)6 (5.7)7 (4.4)3 (3.1)35 (7.6)
Grade ≥3 AEs600 (72.7)66 (62.3)133 (83.6)63 (64.9)338 (73.0)
     Neutropenia369 (44.7)26 (24.5)93 (58.5)41 (42.3)209 (45.1)
     TCP131 (15.9)11 (10.4)34 (21.4)19 (19.6)67 (14.5)
Grade ≥3 infections123 (14.9)17 (16.0)17 (10.7)16 (16.5)73 (15.8)
Grade ≥3 IRRs152 (18.4)25 (23.6)33 (20.8)19 (19.6)75 (16.2)
Any SAE367 (44.5)44 (41.5)61 (38.4)39 (40.2)223 (48.2)
Any fatal AE32 (3.9%)4 (3.8%)4 (2.5%)3 (3.1%)21 (4.5%)


Conclusion
Preliminary safety data from GREEN are in line with the known safety profile of G in similar populations.

Session topic: Innovative therapies in CLL

Keyword(s): Chronic lymphocytic leukemia, Obinutuzumab, Safety

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