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IMMUNOCHEMOTHERAPY WITH OBINUTUZUMAB OR RITUXIMAB IN PREVIOUSLY UNTREATED FOLLICULAR LYMPHOMA (FL) IN THE RANDOMIZED PHASE III GALLIUM STUDY: ANALYSIS BY CHEMOTHERAPY REGIMEN
Author(s):
Wolfgang Hiddemann
,
Wolfgang Hiddemann
Affiliations:
Department of Medicine III,Ludwig-Maximilians-University Munich,Munich,Germany
Anna Maria Barbui
,
Anna Maria Barbui
Affiliations:
Department of Hematology,Azienda Ospedaliera Papa Giovanni XXIII,Bergamo,Italy
Miguel Angel Canales Albendea
,
Miguel Angel Canales Albendea
Affiliations:
Department of Medicine,Hospital Universitario la Paz,Madrid,Spain
Paul K Cannell
,
Paul K Cannell
Affiliations:
Haematology Department,Fiona Stanley Hospital,Murdoch,Australia
Graham P Collins
,
Graham P Collins
Affiliations:
Department of Clinical Haematology,Oxford Cancer and Haematology Centre, Churchill Hospital,Oxford,United Kingdom
Jan Dürig
,
Jan Dürig
Affiliations:
Medical Faculty (Haematology),Universitaetsklinikum Essen,Essen,Germany
Roswitha Forstpointner
,
Roswitha Forstpointner
Affiliations:
Department of Medicine III,Ludwig-Maximilians-University Munich,Munich,Germany
Michael Herold
,
Michael Herold
Affiliations:
Oncology Center,HELIOS-Klinikum Erfurt,Erfurt,Germany
Mark Hertzberg
,
Mark Hertzberg
Affiliations:
Department of Haematology,Prince of Wales Hospital,Sydney,Australia
Magdalena Klanova
,
Magdalena Klanova
Affiliations:
First Faculty of Medicine,Charles University General Hospital and Institute of Pathological Physiology, Charles University,Prague,Czech Republic;Pharma Development Clinical Oncology,F. Hoffmann-La Roche Ltd,Basel,Switzerland
John A Radford
,
John A Radford
Affiliations:
The University of Manchester and The Christie NHS Foundation Trust, Manchester Academic Health Science Centre,Manchester,United Kingdom
Kensei Tobinai
,
Kensei Tobinai
Affiliations:
Department of Hematology,National Cancer Center Hospital,Tokyo,Japan
Alis Burciu
,
Alis Burciu
Affiliations:
Pharma Development Safety and Risk Management,F. Hoffmann-La Roche Ltd,Basel,Switzerland
Günter R Fingerle-Rowson
,
Günter R Fingerle-Rowson
Affiliations:
Pharma Development Clinical Oncology,F. Hoffmann-La Roche Ltd,Basel,Switzerland
Tina Nielsen
,
Tina Nielsen
Affiliations:
Pharma Development Clinical Oncology,F. Hoffmann-La Roche Ltd,Basel,Switzerland
Marcel Wolbers
,
Marcel Wolbers
Affiliations:
Pharma Development Biometrics Biostatistics,F. Hoffmann-La Roche Ltd,Basel,Switzerland
Robert E Marcus
Robert E Marcus
Affiliations:
Department of Haematology,Kings College Hospital,London,United Kingdom
(Abstract release date: 05/18/17) EHA Library. Hiddemann W. 06/25/17; 182062; S775
Wolfgang Hiddemann
Wolfgang Hiddemann
Contributions
PDF Abstract
Abstract

Abstract: S775

Type: Oral Presentation

Presentation during EHA22: On Sunday, June 25, 2017 from 08:15 - 08:30

Location: Hall C

Background
The Phase III GALLIUM study (NCT01332968) showed that obinutuzumab (GA101; G) significantly prolonged PFS in previously untreated FL pts relative to rituximab (R) when combined with chemotherapy (chemo; CHOP, CVP or bendamustine [B]). Grade 3–5 and serious AEs were more common with G-chemo.

Aims
To explore outcomes by immunochemotherapy regimen.

Methods
Pts were aged ≥18 yrs with documented, previously untreated FL (grades 1–3a), advanced disease (stage III/IV or stage II with tumor diameter ≥7cm), ECOG PS 0–2, and requiring treatment according to GELF criteria. Chemo regimen was allocated by center. Pts were randomized 1:1 (stratified by chemo, FLIPI-1 group and geographic region) to R 375mg/m2 on day (D) 1 of each cycle (C) or G 1000mg on D1, 8 and 15 of C1 and D1 of C2–8, for 6 or 8 cycles depending on chemo. Pts with CR or PR at EOI (per Cheson 2007) continued to receive R or G every 2 months for 2 yrs or until progression. The cut-off date for this analysis was September 10 2016. All pts gave informed consent.

Results

1202 FL pts were randomized. Baseline characteristics were generally similar across chemo groups, although B and CVP pts had relatively more comorbidities, e.g. GI and vascular disorders, than CHOP pts. After 41.1 months’ median follow-up, investigator (INV)-assessed PFS remained superior for G-chemo relative to R-chemo (HR, 0.68; 95% CI 0.54–0.87; p=0.0016) with consistent HRs across chemo groups (Figure). HRs for secondary time-to-event endpoints were supportive of the primary analysis. Difference in frequency of grade 3–5 AEs between arms was highest with CHOP and CVP (Table). Rates of second neoplasms and grade 3–5 infections were similar in G and R arms for CHOP and CVP but not for B. In all chemo groups, SAEs were more frequent with G than R, and AEs causing treatment discontinuation and fatal AEs were similar. Reductions in T-cell counts were more pronounced and prolonged in the B group than CHOP or CVP groups.
Table. Safety summary (number (%) of FL pts* with ≥1 AE)
 
G-B(n=338)
R-B(n=338)
G-CHOP(n=193)
R-CHOP(n=203)
G-CVP(n=61)
R-CVP(n=56)
G-chemo(n=595)
R-chemo(n=597)
AEs
338(100)
331(97.9)
191(99.0)
201(99.0)
61(100)
56(100)
593(99.7)
585(98.0)
Grade 3–5 AEs
233(68.9)
228(67.5)
171(88.6)
151(74.4)
42(68.9)
30(53.6)
449(75.5)
409(68.5)
Neutropenia†
100(29.6)
102(30.2)
137(71.0)
111(54.7)
28(45.9)
13(23.2)
265(44.5)
226(37.9)
Leucopenia†
11(3.3)
15(4.4)
39(20.2)
34(16.7)
1(1.6)
1(1.8)
51(8.6)
50(8.4)
Febrile neutropenia†
18(5.3)
13(3.8)
22(11.4)
14(6.9)
2(3.3)
2(3.6)
42(7.1)
29(4.9)
AEs of special interest by category
 
 
 
 
 
 
 
 
Grade 3–5 Infections‡
89(26.3)
66(19.5)
23(11.9)
24(12.4)
8(13.1)
7(12.5)
121(20.3)
98(16.4)
Second neoplasms§
37(10.9)
23(6.8)
9(4.7)
11(5.4)
1(1.6)
2(3.6)
47(7.9)
36(6.0)
SAEs
176(52.1)
160(47.3)
76(39.4)
67(33.0)
26(42.6)
19(33.9)
281(47.2)
246(41.2)
Fatal AEs
20(5.9)
16(4.7)
3(1.6)
4(2.0)
1(1.6)
1(1.8)
24(4.0)
21(3.5)
AEs causing Tx discontinuation
52(15.4)
48(14.2)
32(16.6)
31(15.3)
11(18.0)
9(16.1)
98(16.5)
88(14.7)
*Pts who received ≥1 dose of study drug. Three pts received G but no chemo; †Occurring in >10% of pts in any group; ‡MedDRA SOC ‘Infections and Infestations’; §Malignant or unspecified tumors occurring >6 mo after first study drug intake

Conclusion
In treatment-naive FL pts, PFS was superior with G-chemo relative to R-chemo with consistent effects across chemo regimens. Some differences were seen in safety profiles between chemo regimens, but comparisons may be confounded by the lack of randomization.

Session topic: 19. Indolent Non-Hodgkin lymphoma - Clinical

Keyword(s): Obinutuzumab, Follicular lymphoma, Rituximab

Abstract: S775

Type: Oral Presentation

Presentation during EHA22: On Sunday, June 25, 2017 from 08:15 - 08:30

Location: Hall C

Background
The Phase III GALLIUM study (NCT01332968) showed that obinutuzumab (GA101; G) significantly prolonged PFS in previously untreated FL pts relative to rituximab (R) when combined with chemotherapy (chemo; CHOP, CVP or bendamustine [B]). Grade 3–5 and serious AEs were more common with G-chemo.

Aims
To explore outcomes by immunochemotherapy regimen.

Methods
Pts were aged ≥18 yrs with documented, previously untreated FL (grades 1–3a), advanced disease (stage III/IV or stage II with tumor diameter ≥7cm), ECOG PS 0–2, and requiring treatment according to GELF criteria. Chemo regimen was allocated by center. Pts were randomized 1:1 (stratified by chemo, FLIPI-1 group and geographic region) to R 375mg/m2 on day (D) 1 of each cycle (C) or G 1000mg on D1, 8 and 15 of C1 and D1 of C2–8, for 6 or 8 cycles depending on chemo. Pts with CR or PR at EOI (per Cheson 2007) continued to receive R or G every 2 months for 2 yrs or until progression. The cut-off date for this analysis was September 10 2016. All pts gave informed consent.

Results

1202 FL pts were randomized. Baseline characteristics were generally similar across chemo groups, although B and CVP pts had relatively more comorbidities, e.g. GI and vascular disorders, than CHOP pts. After 41.1 months’ median follow-up, investigator (INV)-assessed PFS remained superior for G-chemo relative to R-chemo (HR, 0.68; 95% CI 0.54–0.87; p=0.0016) with consistent HRs across chemo groups (Figure). HRs for secondary time-to-event endpoints were supportive of the primary analysis. Difference in frequency of grade 3–5 AEs between arms was highest with CHOP and CVP (Table). Rates of second neoplasms and grade 3–5 infections were similar in G and R arms for CHOP and CVP but not for B. In all chemo groups, SAEs were more frequent with G than R, and AEs causing treatment discontinuation and fatal AEs were similar. Reductions in T-cell counts were more pronounced and prolonged in the B group than CHOP or CVP groups.
Table. Safety summary (number (%) of FL pts* with ≥1 AE)
 
G-B(n=338)
R-B(n=338)
G-CHOP(n=193)
R-CHOP(n=203)
G-CVP(n=61)
R-CVP(n=56)
G-chemo(n=595)
R-chemo(n=597)
AEs
338(100)
331(97.9)
191(99.0)
201(99.0)
61(100)
56(100)
593(99.7)
585(98.0)
Grade 3–5 AEs
233(68.9)
228(67.5)
171(88.6)
151(74.4)
42(68.9)
30(53.6)
449(75.5)
409(68.5)
Neutropenia†
100(29.6)
102(30.2)
137(71.0)
111(54.7)
28(45.9)
13(23.2)
265(44.5)
226(37.9)
Leucopenia†
11(3.3)
15(4.4)
39(20.2)
34(16.7)
1(1.6)
1(1.8)
51(8.6)
50(8.4)
Febrile neutropenia†
18(5.3)
13(3.8)
22(11.4)
14(6.9)
2(3.3)
2(3.6)
42(7.1)
29(4.9)
AEs of special interest by category
 
 
 
 
 
 
 
 
Grade 3–5 Infections‡
89(26.3)
66(19.5)
23(11.9)
24(12.4)
8(13.1)
7(12.5)
121(20.3)
98(16.4)
Second neoplasms§
37(10.9)
23(6.8)
9(4.7)
11(5.4)
1(1.6)
2(3.6)
47(7.9)
36(6.0)
SAEs
176(52.1)
160(47.3)
76(39.4)
67(33.0)
26(42.6)
19(33.9)
281(47.2)
246(41.2)
Fatal AEs
20(5.9)
16(4.7)
3(1.6)
4(2.0)
1(1.6)
1(1.8)
24(4.0)
21(3.5)
AEs causing Tx discontinuation
52(15.4)
48(14.2)
32(16.6)
31(15.3)
11(18.0)
9(16.1)
98(16.5)
88(14.7)
*Pts who received ≥1 dose of study drug. Three pts received G but no chemo; †Occurring in >10% of pts in any group; ‡MedDRA SOC ‘Infections and Infestations’; §Malignant or unspecified tumors occurring >6 mo after first study drug intake

Conclusion
In treatment-naive FL pts, PFS was superior with G-chemo relative to R-chemo with consistent effects across chemo regimens. Some differences were seen in safety profiles between chemo regimens, but comparisons may be confounded by the lack of randomization.

Session topic: 19. Indolent Non-Hodgkin lymphoma - Clinical

Keyword(s): Obinutuzumab, Follicular lymphoma, Rituximab

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