RANDOMIZED PHASE III STUDY OF EARLY RITUXIMAB INTENSIFICATION IN COMBINATION WITH CHOP14 FOLLOWED BY RITUXIMAB OR NO MAINTENANCE IN DIFFUSE LARGE B-CELL LYMPHOMA: A HOVON-NORDIC LYMPHOMA GROUP STUDY
(Abstract release date: 05/19/16)
EHA Library. Lugtenburg P. 06/11/16; 135233; S477
Dr. Pieternella (Elly) Lugtenburg
Contributions
Contributions
Abstract
Abstract: S477
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:00 - 16:15
Location: Hall A1
Background
Rituximab (R)-CHOP is standard treatment for patients with diffuse large B-cell lymphoma (DLBCL). The optimal R dose and schedule is not known. In a small series of 20 patients serum levels of R, measured during the R-CHOP-14 regimen in elderly patients with DLBCL increased slowly up to cycle 5, reaching plateau thereafter (Reiser M, et al. J Clin Oncol 2006). We hypothesized that R serum levels might be suboptimal, especially early during treatment, and that the treatment outcome might improve through intensification of R during the first 4 cycles. In this study designed for both young and elderly DLBCL patients we compared standard treatment of R-CHOP-14 with the same regimen combined with 4 extra R administrations during the first 4 cycles. Patients in complete remission after induction treatment were randomized for a second time between observation and R maintenance. Here we report the efficacy and safety results of the first randomization.
Aims
This phase III, open-label randomized study was designed to detect superior metabolic complete remission rates of early intensification of R combined with CHOP-14 + G-CSF versus no intensification of rituximab in patients with DLBCL of all age groups.
Methods
Patients with previously untreated DLBCL, CD20 positive, stage II-IV, ages between 18-80 years, were randomized 1:1 between standard R-CHOP-14 and an experimental arm with R-CHOP-14 combined with extra R 375 mg/m2 IV on day 8 of the first 4 cycles. Prephase treatment of prednisone 100 mg orally for 5 days was mandatory in elderly patients. All patients received pegfilgrastim 6 mg sc on day 2. All patients underwent restaging after 4 cycles of therapy and at the end of induction therapy. Response was evaluated using PET-CT scans according to the Lugano criteria 2014. A Deauville score of ≤ 3 was considered as a complete response. The primary endpoint of the first randomization was metabolic complete remission rate after induction treatment. This trial was registered at www.trialregister.nl as NTR1014. All patients gave written informed consent.
Results
575 patients were randomized (standard arm 286 patients, experimental arm 289 patients). Median age was 65 years (range, 18-80), 50% of patients were 66 years or older and 52% were male. The majority of patients (57%) had a high-intermediate or high aa-IPI score. Baseline patient and disease characteristics were well balanced between treatment arms. No significant difference in CR rate was observed between the two treatment arms, standard arm 84% CR and experimental arm 82% CR (odds ratio = 0.83, 95% CI 0.54-1.28, p = 0.40). The observed CR rates in patients ≤ or > 65 years were identical. With a median follow-up of 49 months (maximum 90 months), 3- and 5- year progression free survival (PFS) were 74% and 68% in the standard arm and 71% and 61% in the experimental arm (hazard ratio = 1.23, 95% CI 0.92-1.63, p = 0.16). No significant improvement in PFS was noted in subgroups by age ( ≤ or > 65 years) or gender. The frequencies of hematological and non-hematological adverse events were similar in both treatment arms.
Conclusion
In patients with DLBCL treated with R-CHOP-14 rituximab intensification early during treatment did not improve the CR rate or the 3-year PFS. No clinical subgroup benefited from rituximab intensification in this study.
Session topic: Diffuse large B-cell lymphoma
Keyword(s): CHOP, DLBCL, Phase III, Rituximab
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:00 - 16:15
Location: Hall A1
Background
Rituximab (R)-CHOP is standard treatment for patients with diffuse large B-cell lymphoma (DLBCL). The optimal R dose and schedule is not known. In a small series of 20 patients serum levels of R, measured during the R-CHOP-14 regimen in elderly patients with DLBCL increased slowly up to cycle 5, reaching plateau thereafter (Reiser M, et al. J Clin Oncol 2006). We hypothesized that R serum levels might be suboptimal, especially early during treatment, and that the treatment outcome might improve through intensification of R during the first 4 cycles. In this study designed for both young and elderly DLBCL patients we compared standard treatment of R-CHOP-14 with the same regimen combined with 4 extra R administrations during the first 4 cycles. Patients in complete remission after induction treatment were randomized for a second time between observation and R maintenance. Here we report the efficacy and safety results of the first randomization.
Aims
This phase III, open-label randomized study was designed to detect superior metabolic complete remission rates of early intensification of R combined with CHOP-14 + G-CSF versus no intensification of rituximab in patients with DLBCL of all age groups.
Methods
Patients with previously untreated DLBCL, CD20 positive, stage II-IV, ages between 18-80 years, were randomized 1:1 between standard R-CHOP-14 and an experimental arm with R-CHOP-14 combined with extra R 375 mg/m2 IV on day 8 of the first 4 cycles. Prephase treatment of prednisone 100 mg orally for 5 days was mandatory in elderly patients. All patients received pegfilgrastim 6 mg sc on day 2. All patients underwent restaging after 4 cycles of therapy and at the end of induction therapy. Response was evaluated using PET-CT scans according to the Lugano criteria 2014. A Deauville score of ≤ 3 was considered as a complete response. The primary endpoint of the first randomization was metabolic complete remission rate after induction treatment. This trial was registered at www.trialregister.nl as NTR1014. All patients gave written informed consent.
Results
575 patients were randomized (standard arm 286 patients, experimental arm 289 patients). Median age was 65 years (range, 18-80), 50% of patients were 66 years or older and 52% were male. The majority of patients (57%) had a high-intermediate or high aa-IPI score. Baseline patient and disease characteristics were well balanced between treatment arms. No significant difference in CR rate was observed between the two treatment arms, standard arm 84% CR and experimental arm 82% CR (odds ratio = 0.83, 95% CI 0.54-1.28, p = 0.40). The observed CR rates in patients ≤ or > 65 years were identical. With a median follow-up of 49 months (maximum 90 months), 3- and 5- year progression free survival (PFS) were 74% and 68% in the standard arm and 71% and 61% in the experimental arm (hazard ratio = 1.23, 95% CI 0.92-1.63, p = 0.16). No significant improvement in PFS was noted in subgroups by age ( ≤ or > 65 years) or gender. The frequencies of hematological and non-hematological adverse events were similar in both treatment arms.
Conclusion
In patients with DLBCL treated with R-CHOP-14 rituximab intensification early during treatment did not improve the CR rate or the 3-year PFS. No clinical subgroup benefited from rituximab intensification in this study.
Session topic: Diffuse large B-cell lymphoma
Keyword(s): CHOP, DLBCL, Phase III, Rituximab
Abstract: S477
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:00 - 16:15
Location: Hall A1
Background
Rituximab (R)-CHOP is standard treatment for patients with diffuse large B-cell lymphoma (DLBCL). The optimal R dose and schedule is not known. In a small series of 20 patients serum levels of R, measured during the R-CHOP-14 regimen in elderly patients with DLBCL increased slowly up to cycle 5, reaching plateau thereafter (Reiser M, et al. J Clin Oncol 2006). We hypothesized that R serum levels might be suboptimal, especially early during treatment, and that the treatment outcome might improve through intensification of R during the first 4 cycles. In this study designed for both young and elderly DLBCL patients we compared standard treatment of R-CHOP-14 with the same regimen combined with 4 extra R administrations during the first 4 cycles. Patients in complete remission after induction treatment were randomized for a second time between observation and R maintenance. Here we report the efficacy and safety results of the first randomization.
Aims
This phase III, open-label randomized study was designed to detect superior metabolic complete remission rates of early intensification of R combined with CHOP-14 + G-CSF versus no intensification of rituximab in patients with DLBCL of all age groups.
Methods
Patients with previously untreated DLBCL, CD20 positive, stage II-IV, ages between 18-80 years, were randomized 1:1 between standard R-CHOP-14 and an experimental arm with R-CHOP-14 combined with extra R 375 mg/m2 IV on day 8 of the first 4 cycles. Prephase treatment of prednisone 100 mg orally for 5 days was mandatory in elderly patients. All patients received pegfilgrastim 6 mg sc on day 2. All patients underwent restaging after 4 cycles of therapy and at the end of induction therapy. Response was evaluated using PET-CT scans according to the Lugano criteria 2014. A Deauville score of ≤ 3 was considered as a complete response. The primary endpoint of the first randomization was metabolic complete remission rate after induction treatment. This trial was registered at www.trialregister.nl as NTR1014. All patients gave written informed consent.
Results
575 patients were randomized (standard arm 286 patients, experimental arm 289 patients). Median age was 65 years (range, 18-80), 50% of patients were 66 years or older and 52% were male. The majority of patients (57%) had a high-intermediate or high aa-IPI score. Baseline patient and disease characteristics were well balanced between treatment arms. No significant difference in CR rate was observed between the two treatment arms, standard arm 84% CR and experimental arm 82% CR (odds ratio = 0.83, 95% CI 0.54-1.28, p = 0.40). The observed CR rates in patients ≤ or > 65 years were identical. With a median follow-up of 49 months (maximum 90 months), 3- and 5- year progression free survival (PFS) were 74% and 68% in the standard arm and 71% and 61% in the experimental arm (hazard ratio = 1.23, 95% CI 0.92-1.63, p = 0.16). No significant improvement in PFS was noted in subgroups by age ( ≤ or > 65 years) or gender. The frequencies of hematological and non-hematological adverse events were similar in both treatment arms.
Conclusion
In patients with DLBCL treated with R-CHOP-14 rituximab intensification early during treatment did not improve the CR rate or the 3-year PFS. No clinical subgroup benefited from rituximab intensification in this study.
Session topic: Diffuse large B-cell lymphoma
Keyword(s): CHOP, DLBCL, Phase III, Rituximab
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:00 - 16:15
Location: Hall A1
Background
Rituximab (R)-CHOP is standard treatment for patients with diffuse large B-cell lymphoma (DLBCL). The optimal R dose and schedule is not known. In a small series of 20 patients serum levels of R, measured during the R-CHOP-14 regimen in elderly patients with DLBCL increased slowly up to cycle 5, reaching plateau thereafter (Reiser M, et al. J Clin Oncol 2006). We hypothesized that R serum levels might be suboptimal, especially early during treatment, and that the treatment outcome might improve through intensification of R during the first 4 cycles. In this study designed for both young and elderly DLBCL patients we compared standard treatment of R-CHOP-14 with the same regimen combined with 4 extra R administrations during the first 4 cycles. Patients in complete remission after induction treatment were randomized for a second time between observation and R maintenance. Here we report the efficacy and safety results of the first randomization.
Aims
This phase III, open-label randomized study was designed to detect superior metabolic complete remission rates of early intensification of R combined with CHOP-14 + G-CSF versus no intensification of rituximab in patients with DLBCL of all age groups.
Methods
Patients with previously untreated DLBCL, CD20 positive, stage II-IV, ages between 18-80 years, were randomized 1:1 between standard R-CHOP-14 and an experimental arm with R-CHOP-14 combined with extra R 375 mg/m2 IV on day 8 of the first 4 cycles. Prephase treatment of prednisone 100 mg orally for 5 days was mandatory in elderly patients. All patients received pegfilgrastim 6 mg sc on day 2. All patients underwent restaging after 4 cycles of therapy and at the end of induction therapy. Response was evaluated using PET-CT scans according to the Lugano criteria 2014. A Deauville score of ≤ 3 was considered as a complete response. The primary endpoint of the first randomization was metabolic complete remission rate after induction treatment. This trial was registered at www.trialregister.nl as NTR1014. All patients gave written informed consent.
Results
575 patients were randomized (standard arm 286 patients, experimental arm 289 patients). Median age was 65 years (range, 18-80), 50% of patients were 66 years or older and 52% were male. The majority of patients (57%) had a high-intermediate or high aa-IPI score. Baseline patient and disease characteristics were well balanced between treatment arms. No significant difference in CR rate was observed between the two treatment arms, standard arm 84% CR and experimental arm 82% CR (odds ratio = 0.83, 95% CI 0.54-1.28, p = 0.40). The observed CR rates in patients ≤ or > 65 years were identical. With a median follow-up of 49 months (maximum 90 months), 3- and 5- year progression free survival (PFS) were 74% and 68% in the standard arm and 71% and 61% in the experimental arm (hazard ratio = 1.23, 95% CI 0.92-1.63, p = 0.16). No significant improvement in PFS was noted in subgroups by age ( ≤ or > 65 years) or gender. The frequencies of hematological and non-hematological adverse events were similar in both treatment arms.
Conclusion
In patients with DLBCL treated with R-CHOP-14 rituximab intensification early during treatment did not improve the CR rate or the 3-year PFS. No clinical subgroup benefited from rituximab intensification in this study.
Session topic: Diffuse large B-cell lymphoma
Keyword(s): CHOP, DLBCL, Phase III, Rituximab
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