OBINUTUZUMAB PLUS BENDAMUSTINE VERSUS BENDAMUSTINE ALONE IN PATIENTS WITH RITUXIMAB-REFRACTORY FOLLICULAR LYMPHOMA: RESULTS FROM THE GADOLIN STUDY
(Abstract release date: 05/19/16)
EHA Library. Trneny M. 06/11/16; 135196; S440
Prof. Dr. Marek Trneny
Contributions
Contributions
Abstract
Abstract: S440
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 12:15 - 12:30
Location: Auditorium 1
Background
Limited treatment options are available for patients (pts) with rituximab-refractory (R-R) indolent non-Hodgkin lymphoma (iNHL). GADOLIN (NCT01059630) is an open-label, randomized, phase 3 trial comparing the efficacy and safety of obinutuzumab (GA101; GAZYVA/GAZYVARO; G) plus bendamustine (B; G-B) induction, followed by G maintenance, with B standard of care in this pt group. In the primary analysis (median observation time: 21 months [mo]) of iNHL pts, median Independent-Review Committee (IRC)-assessed progression-free survival (PFS) was longer in the G-B arm (194 pts; median not reached) than in the B arm (202 pts; 14.9 mo), with a 45% reduction in risk of progression or death (HR 0.55; 95% CI 0.40-0.74; p=0.0001). Safety profiles were comparable.
Aims
To evaluate efficacy and safety in the follicular lymphoma (FL) subset of GADOLIN pts considered in the primary analysis.
Methods
GADOLIN pts were aged ≥18 years with documented R-R iNHL and an Eastern Cooperative Oncology Group performance status of 0-2. Pts received either G 1000mg intravenously (IV) (days [D] 1, 8 and 15 of cycle (C) 1 and D1 of C2-6) plus B 90mg/m2/day IV (D1 and 2 of C1-6) or B monotherapy (120mg/m2/day IV D1 and 2 of each cycle for up to six cycles); each cycle was 28 days. Following induction, pts in the G-B arm without evidence of progression received G maintenance (1000mg IV every 2 mo for 2 years or until disease progression). Endpoints included IRC-assessed PFS (primary), investigator (INV)-assessed PFS, response and safety. All pts gave informed consent.
Results
321 (81%) of 396 iNHL pts enrolled had FL (G-B, 155; B, 166). Baseline characteristics of the FL population were balanced between arms. Median number of prior therapies was 2. Most pts were refractory to their last prior rituximab (R)-containing regimen (G-B, 94%; B, 93%) and double-refractory to R and an alkylating agent (G-B, 77%; B, 80%). IRC-assessed end of induction (EOI) and best overall response were similar in the G-B and B arms (p>0.05 for comparison; Table). Median IRC-assessed PFS was not reached in the G-B arm and was 13.8 mo in the B arm (Figure), while median INV-assessed PFS was more than twice as long in the G-B arm than in the B arm (Table); in both instances, the advantage corresponded to a 52% reduction in risk of progression or death relative to B (Table). Survival data were immature at the time of analysis. Safety profiles were comparable. Of note, grade 3-5 adverse events (AEs) and grade 5 AEs (fatal outcome) occurred in 65.8% and 5.2% pts in the G-B arm and 58.9% and 6.1% pts in the B arm, respectively.
Conclusion
In the FL subset of GADOLIN pts, PFS was significantly longer in the G-B arm compared with the B arm, corresponding to a 52% reduction in risk of progression or death. No unexpected safety signals were identified. G-B is an effective therapy for pts with R-R FL.
Session topic: Follicular and Mantle Cell Lymphoma - Clinical
Keyword(s): Bendamustine, Follicular lymphoma, Indolent non-Hodgkin's lymphoma, Obinutuzumab
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 12:15 - 12:30
Location: Auditorium 1
Background
Limited treatment options are available for patients (pts) with rituximab-refractory (R-R) indolent non-Hodgkin lymphoma (iNHL). GADOLIN (NCT01059630) is an open-label, randomized, phase 3 trial comparing the efficacy and safety of obinutuzumab (GA101; GAZYVA/GAZYVARO; G) plus bendamustine (B; G-B) induction, followed by G maintenance, with B standard of care in this pt group. In the primary analysis (median observation time: 21 months [mo]) of iNHL pts, median Independent-Review Committee (IRC)-assessed progression-free survival (PFS) was longer in the G-B arm (194 pts; median not reached) than in the B arm (202 pts; 14.9 mo), with a 45% reduction in risk of progression or death (HR 0.55; 95% CI 0.40-0.74; p=0.0001). Safety profiles were comparable.
Aims
To evaluate efficacy and safety in the follicular lymphoma (FL) subset of GADOLIN pts considered in the primary analysis.
Methods
GADOLIN pts were aged ≥18 years with documented R-R iNHL and an Eastern Cooperative Oncology Group performance status of 0-2. Pts received either G 1000mg intravenously (IV) (days [D] 1, 8 and 15 of cycle (C) 1 and D1 of C2-6) plus B 90mg/m2/day IV (D1 and 2 of C1-6) or B monotherapy (120mg/m2/day IV D1 and 2 of each cycle for up to six cycles); each cycle was 28 days. Following induction, pts in the G-B arm without evidence of progression received G maintenance (1000mg IV every 2 mo for 2 years or until disease progression). Endpoints included IRC-assessed PFS (primary), investigator (INV)-assessed PFS, response and safety. All pts gave informed consent.
Results
321 (81%) of 396 iNHL pts enrolled had FL (G-B, 155; B, 166). Baseline characteristics of the FL population were balanced between arms. Median number of prior therapies was 2. Most pts were refractory to their last prior rituximab (R)-containing regimen (G-B, 94%; B, 93%) and double-refractory to R and an alkylating agent (G-B, 77%; B, 80%). IRC-assessed end of induction (EOI) and best overall response were similar in the G-B and B arms (p>0.05 for comparison; Table). Median IRC-assessed PFS was not reached in the G-B arm and was 13.8 mo in the B arm (Figure), while median INV-assessed PFS was more than twice as long in the G-B arm than in the B arm (Table); in both instances, the advantage corresponded to a 52% reduction in risk of progression or death relative to B (Table). Survival data were immature at the time of analysis. Safety profiles were comparable. Of note, grade 3-5 adverse events (AEs) and grade 5 AEs (fatal outcome) occurred in 65.8% and 5.2% pts in the G-B arm and 58.9% and 6.1% pts in the B arm, respectively.
| Parameter | FL subpopulation | |
| G-B (n=155) | B (n=166) | |
| Median observation time (range), mo | 22.08 (0.4-48.5) | 20.27 (0.0-50.0) |
| PFS (IRC) | ||
| Pts with event, n (%) | 54 (34.8) | 90 (54.2) |
| Median (mo) | Not reached | 13.8 |
| HR [95% CI]; stratified* | 0.48 [0.34-0.68] | |
| PFS (INV) | ||
| Pts with event, n (%) | 62 (40.0) | 102 (61.4) |
| Median (mo) | 29.2 | 13.7 |
| HR [95% CI]; stratified* | 0.48 [0.35-0.67] | |
| Response† (IRC) | ||
| EOI response (%): overall‡/CR | 70.5/9.4 | 62.6/13.5 |
| Best response (%): overall‡/CR | 79.7/15.7 | 77.0/19.3 |
| *Stratification factors for FL population were refractory type (R vs R-chemo) and prior therapies (≤2 vs >2); †During treatment and within 12 mo after start of treatment; ‡Complete response (CR) or partial response | ||
Conclusion
In the FL subset of GADOLIN pts, PFS was significantly longer in the G-B arm compared with the B arm, corresponding to a 52% reduction in risk of progression or death. No unexpected safety signals were identified. G-B is an effective therapy for pts with R-R FL.
Session topic: Follicular and Mantle Cell Lymphoma - Clinical
Keyword(s): Bendamustine, Follicular lymphoma, Indolent non-Hodgkin's lymphoma, Obinutuzumab
Abstract: S440
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 12:15 - 12:30
Location: Auditorium 1
Background
Limited treatment options are available for patients (pts) with rituximab-refractory (R-R) indolent non-Hodgkin lymphoma (iNHL). GADOLIN (NCT01059630) is an open-label, randomized, phase 3 trial comparing the efficacy and safety of obinutuzumab (GA101; GAZYVA/GAZYVARO; G) plus bendamustine (B; G-B) induction, followed by G maintenance, with B standard of care in this pt group. In the primary analysis (median observation time: 21 months [mo]) of iNHL pts, median Independent-Review Committee (IRC)-assessed progression-free survival (PFS) was longer in the G-B arm (194 pts; median not reached) than in the B arm (202 pts; 14.9 mo), with a 45% reduction in risk of progression or death (HR 0.55; 95% CI 0.40-0.74; p=0.0001). Safety profiles were comparable.
Aims
To evaluate efficacy and safety in the follicular lymphoma (FL) subset of GADOLIN pts considered in the primary analysis.
Methods
GADOLIN pts were aged ≥18 years with documented R-R iNHL and an Eastern Cooperative Oncology Group performance status of 0-2. Pts received either G 1000mg intravenously (IV) (days [D] 1, 8 and 15 of cycle (C) 1 and D1 of C2-6) plus B 90mg/m2/day IV (D1 and 2 of C1-6) or B monotherapy (120mg/m2/day IV D1 and 2 of each cycle for up to six cycles); each cycle was 28 days. Following induction, pts in the G-B arm without evidence of progression received G maintenance (1000mg IV every 2 mo for 2 years or until disease progression). Endpoints included IRC-assessed PFS (primary), investigator (INV)-assessed PFS, response and safety. All pts gave informed consent.
Results
321 (81%) of 396 iNHL pts enrolled had FL (G-B, 155; B, 166). Baseline characteristics of the FL population were balanced between arms. Median number of prior therapies was 2. Most pts were refractory to their last prior rituximab (R)-containing regimen (G-B, 94%; B, 93%) and double-refractory to R and an alkylating agent (G-B, 77%; B, 80%). IRC-assessed end of induction (EOI) and best overall response were similar in the G-B and B arms (p>0.05 for comparison; Table). Median IRC-assessed PFS was not reached in the G-B arm and was 13.8 mo in the B arm (Figure), while median INV-assessed PFS was more than twice as long in the G-B arm than in the B arm (Table); in both instances, the advantage corresponded to a 52% reduction in risk of progression or death relative to B (Table). Survival data were immature at the time of analysis. Safety profiles were comparable. Of note, grade 3-5 adverse events (AEs) and grade 5 AEs (fatal outcome) occurred in 65.8% and 5.2% pts in the G-B arm and 58.9% and 6.1% pts in the B arm, respectively.
Conclusion
In the FL subset of GADOLIN pts, PFS was significantly longer in the G-B arm compared with the B arm, corresponding to a 52% reduction in risk of progression or death. No unexpected safety signals were identified. G-B is an effective therapy for pts with R-R FL.
Session topic: Follicular and Mantle Cell Lymphoma - Clinical
Keyword(s): Bendamustine, Follicular lymphoma, Indolent non-Hodgkin's lymphoma, Obinutuzumab
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 12:15 - 12:30
Location: Auditorium 1
Background
Limited treatment options are available for patients (pts) with rituximab-refractory (R-R) indolent non-Hodgkin lymphoma (iNHL). GADOLIN (NCT01059630) is an open-label, randomized, phase 3 trial comparing the efficacy and safety of obinutuzumab (GA101; GAZYVA/GAZYVARO; G) plus bendamustine (B; G-B) induction, followed by G maintenance, with B standard of care in this pt group. In the primary analysis (median observation time: 21 months [mo]) of iNHL pts, median Independent-Review Committee (IRC)-assessed progression-free survival (PFS) was longer in the G-B arm (194 pts; median not reached) than in the B arm (202 pts; 14.9 mo), with a 45% reduction in risk of progression or death (HR 0.55; 95% CI 0.40-0.74; p=0.0001). Safety profiles were comparable.
Aims
To evaluate efficacy and safety in the follicular lymphoma (FL) subset of GADOLIN pts considered in the primary analysis.
Methods
GADOLIN pts were aged ≥18 years with documented R-R iNHL and an Eastern Cooperative Oncology Group performance status of 0-2. Pts received either G 1000mg intravenously (IV) (days [D] 1, 8 and 15 of cycle (C) 1 and D1 of C2-6) plus B 90mg/m2/day IV (D1 and 2 of C1-6) or B monotherapy (120mg/m2/day IV D1 and 2 of each cycle for up to six cycles); each cycle was 28 days. Following induction, pts in the G-B arm without evidence of progression received G maintenance (1000mg IV every 2 mo for 2 years or until disease progression). Endpoints included IRC-assessed PFS (primary), investigator (INV)-assessed PFS, response and safety. All pts gave informed consent.
Results
321 (81%) of 396 iNHL pts enrolled had FL (G-B, 155; B, 166). Baseline characteristics of the FL population were balanced between arms. Median number of prior therapies was 2. Most pts were refractory to their last prior rituximab (R)-containing regimen (G-B, 94%; B, 93%) and double-refractory to R and an alkylating agent (G-B, 77%; B, 80%). IRC-assessed end of induction (EOI) and best overall response were similar in the G-B and B arms (p>0.05 for comparison; Table). Median IRC-assessed PFS was not reached in the G-B arm and was 13.8 mo in the B arm (Figure), while median INV-assessed PFS was more than twice as long in the G-B arm than in the B arm (Table); in both instances, the advantage corresponded to a 52% reduction in risk of progression or death relative to B (Table). Survival data were immature at the time of analysis. Safety profiles were comparable. Of note, grade 3-5 adverse events (AEs) and grade 5 AEs (fatal outcome) occurred in 65.8% and 5.2% pts in the G-B arm and 58.9% and 6.1% pts in the B arm, respectively.
| Parameter | FL subpopulation | |
| G-B (n=155) | B (n=166) | |
| Median observation time (range), mo | 22.08 (0.4-48.5) | 20.27 (0.0-50.0) |
| PFS (IRC) | ||
| Pts with event, n (%) | 54 (34.8) | 90 (54.2) |
| Median (mo) | Not reached | 13.8 |
| HR [95% CI]; stratified* | 0.48 [0.34-0.68] | |
| PFS (INV) | ||
| Pts with event, n (%) | 62 (40.0) | 102 (61.4) |
| Median (mo) | 29.2 | 13.7 |
| HR [95% CI]; stratified* | 0.48 [0.35-0.67] | |
| Response† (IRC) | ||
| EOI response (%): overall‡/CR | 70.5/9.4 | 62.6/13.5 |
| Best response (%): overall‡/CR | 79.7/15.7 | 77.0/19.3 |
| *Stratification factors for FL population were refractory type (R vs R-chemo) and prior therapies (≤2 vs >2); †During treatment and within 12 mo after start of treatment; ‡Complete response (CR) or partial response | ||
Conclusion
In the FL subset of GADOLIN pts, PFS was significantly longer in the G-B arm compared with the B arm, corresponding to a 52% reduction in risk of progression or death. No unexpected safety signals were identified. G-B is an effective therapy for pts with R-R FL.
Session topic: Follicular and Mantle Cell Lymphoma - Clinical
Keyword(s): Bendamustine, Follicular lymphoma, Indolent non-Hodgkin's lymphoma, Obinutuzumab
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