Contributions
Abstract: PB1870
Type: Publication Only
Background
Combination of bendamustine and rituximab has been established in many international guidelines as treatment for patients with indolent B-cell non-Hodgkin lymphoma (iNHL).
Aims
Objectives of this study were to evaluate the effectiveness, safety, and tolerability of bendamustine/rituximab combination followed by rituximab maintenance therapy for relapsed or refractory (R/R) iNHL patients in the Russian Federation.
Methods
Adult subjects (≥18 yr), diagnosed with R/R iNHL according to local diagnostic standards, and were enrolled in this prospective observational study. Intravenous therapy was administered in 2 stages (Figure): a combination therapy stage followed by a rituximab supporting therapy stage for subjects who achieved complete response (CR) or partial response (PR) during the combination therapy stage. Overall response rate (ORR) was assessed after 3 (Evaluation 1) and 6–8 (Evaluation 2) 28-day cycles. Data from the full analysis set (FAS) were used for the primary analysis and the per-protocol (PP) set for a subgroup analysis. Safety/tolerability was a secondary endpoint and was assessed in the safety analysis set (SAF). Response assessments used the LOCF method for substitution of missing data; overall survival (OS) and progression-free survival (PFS) were calculated using Kaplan–Meier estimates, safety/tolerability was assessed by adverse event (AE) frequency and described using descriptive statistics.
Results
Of the 102 subjects enrolled between June 2012 and October 2015, 83 subjects (52M/31F; median age 59 yr [range: 27–84]) with various NHL histology; subjects with mantle cell lymphoma [n=4], diffuse large B-cell lymphoma [n=2], and follicular lymphoma transformation [n=1] were excluded from the PP population due to deviation from the iNHL inclusion criteria. Most study subjects were heavily pretreated with a median number of 2 prior lines of therapy before entering the study (range: 1–6). At Evaluation 2, ORR in the FAS was high (n=58; 69.9%) with 35 (42.2%) subjects achieving CR (confirmed, n=20 [24.1%]; unconfirmed, n=15 [18.1%]) and 23 (27.7%) achieving PR; ORR (defined as [CR+CR unconfirmed +PR]) in the PP population was 70.8% (Table). For FAS patients, at follow up (17 mo) neither median OS nor PFS had been reached; 2-year OS was 88.9% (95% CI: 79.7–99.0%) and 2-year PFS was 87.9% (95% CI: 80.7–95.7%). In the SAF, 31 of 96 subjects (32.3%) reported ≥1 AE. Decreased neutrophil count, decreased white blood cell count, and infections were the most commonly reported AEs and serious AEs. Twelve deaths occurred: 5 due to disease progression (n=2) or relapse (n=3), 5 were not related to lymphoma or occurred during remission, 1 cause of death was unknown, and 1 subject died from hyperthermia and respiratory failure, which was the only death in the study considered related to combination therapy.
FAS Population (n=81) | PP Population (n=72) | |||
Evaluation 1 | Evaluation 2 | Evaluation 1 | Evaluation 2 | |
ORR, n (%) | 56 (67.5) | 58 (69.9) | 49 (68.1) | 51 (70.8) |
CR/CRu | 24 (28.9) | 35 (42.2) | 22 (30.6) | 33 (45.8) |
PR | 32 (38.6) | 23 (27.7) | 27 (37.5) | 18 (25.0) |
Conclusion
Bendamustine plus rituximab therapy followed by rituximab maintenance therapy was generally well tolerated and demonstrated clinical effectiveness in Russian R/R patients with iNHLs. Although a number of subjects with aggressive lymphomas were included in the FAS, the ORR rate was not considerably different from the PP population (ORR: 69.9% [FAS] vs 70.8% [PP]).
Session topic: 19. Indolent Non-Hodgkin lymphoma - Clinical
Keyword(s): Rituximab, Indolent Non-Hodgkin's Lymphoma, bendamustine
Abstract: PB1870
Type: Publication Only
Background
Combination of bendamustine and rituximab has been established in many international guidelines as treatment for patients with indolent B-cell non-Hodgkin lymphoma (iNHL).
Aims
Objectives of this study were to evaluate the effectiveness, safety, and tolerability of bendamustine/rituximab combination followed by rituximab maintenance therapy for relapsed or refractory (R/R) iNHL patients in the Russian Federation.
Methods
Adult subjects (≥18 yr), diagnosed with R/R iNHL according to local diagnostic standards, and were enrolled in this prospective observational study. Intravenous therapy was administered in 2 stages (Figure): a combination therapy stage followed by a rituximab supporting therapy stage for subjects who achieved complete response (CR) or partial response (PR) during the combination therapy stage. Overall response rate (ORR) was assessed after 3 (Evaluation 1) and 6–8 (Evaluation 2) 28-day cycles. Data from the full analysis set (FAS) were used for the primary analysis and the per-protocol (PP) set for a subgroup analysis. Safety/tolerability was a secondary endpoint and was assessed in the safety analysis set (SAF). Response assessments used the LOCF method for substitution of missing data; overall survival (OS) and progression-free survival (PFS) were calculated using Kaplan–Meier estimates, safety/tolerability was assessed by adverse event (AE) frequency and described using descriptive statistics.
Results
Of the 102 subjects enrolled between June 2012 and October 2015, 83 subjects (52M/31F; median age 59 yr [range: 27–84]) with various NHL histology; subjects with mantle cell lymphoma [n=4], diffuse large B-cell lymphoma [n=2], and follicular lymphoma transformation [n=1] were excluded from the PP population due to deviation from the iNHL inclusion criteria. Most study subjects were heavily pretreated with a median number of 2 prior lines of therapy before entering the study (range: 1–6). At Evaluation 2, ORR in the FAS was high (n=58; 69.9%) with 35 (42.2%) subjects achieving CR (confirmed, n=20 [24.1%]; unconfirmed, n=15 [18.1%]) and 23 (27.7%) achieving PR; ORR (defined as [CR+CR unconfirmed +PR]) in the PP population was 70.8% (Table). For FAS patients, at follow up (17 mo) neither median OS nor PFS had been reached; 2-year OS was 88.9% (95% CI: 79.7–99.0%) and 2-year PFS was 87.9% (95% CI: 80.7–95.7%). In the SAF, 31 of 96 subjects (32.3%) reported ≥1 AE. Decreased neutrophil count, decreased white blood cell count, and infections were the most commonly reported AEs and serious AEs. Twelve deaths occurred: 5 due to disease progression (n=2) or relapse (n=3), 5 were not related to lymphoma or occurred during remission, 1 cause of death was unknown, and 1 subject died from hyperthermia and respiratory failure, which was the only death in the study considered related to combination therapy.
FAS Population (n=81) | PP Population (n=72) | |||
Evaluation 1 | Evaluation 2 | Evaluation 1 | Evaluation 2 | |
ORR, n (%) | 56 (67.5) | 58 (69.9) | 49 (68.1) | 51 (70.8) |
CR/CRu | 24 (28.9) | 35 (42.2) | 22 (30.6) | 33 (45.8) |
PR | 32 (38.6) | 23 (27.7) | 27 (37.5) | 18 (25.0) |
Conclusion
Bendamustine plus rituximab therapy followed by rituximab maintenance therapy was generally well tolerated and demonstrated clinical effectiveness in Russian R/R patients with iNHLs. Although a number of subjects with aggressive lymphomas were included in the FAS, the ORR rate was not considerably different from the PP population (ORR: 69.9% [FAS] vs 70.8% [PP]).
Session topic: 19. Indolent Non-Hodgkin lymphoma - Clinical
Keyword(s): Rituximab, Indolent Non-Hodgkin's Lymphoma, bendamustine