LONG-TERM FOLLOW-UP OF CONTEMPORARY TREATMENT IN EARLY-STAGE HODGKIN LYMPHOMA (HL): UPDATED ANALYSES OF THE GERMAN HODGKIN STUDY GROUP HD7, HD8, HD10 AND HD11 TRIALS
(Abstract release date: 05/19/16)
EHA Library. Bröckelmann P. 06/10/16; 135139; S106
Dr. Paul Bröckelmann
Contributions
Contributions
Abstract
Abstract: S106
Type: Oral Presentation
Presentation during EHA21: On Friday, June 10, 2016 from 11:45 - 12:00
Location: Hall A2
Background
Combined modality treatment (CMT) is currently considered as standard of care in patients with early-stage HL. During the years, a gradual toxicity reduction through balancing extent and intensity of radiotherapy (RT) and chemotherapy was achieved.
Aims
We evaluated long-term follow-up (FU) of pivotal trials, to ensure the applied therapies are safe and beneficial for our patients.
Methods
We analyzed updated FU data of 4299 patients who were treated for primary early-stage HL in previously published GHSG trials between 1993 and 2003. Patients with favorable disease were randomized in HD 7 to either CMT with 2xABVD or to 40Gy extended-field (EF)-RT only, and in HD10 to either 4x or 2xABVD and 20 or 30Gy involved-field (IF)-RT, respectively. Patients with unfavorable HL in HD8 had received either 30Gy IF- or extended-field (EF)-RT after 2xCOPP/ABVD and in HD11 either 20 or 30Gy IF-RT after 4xABVD or 4xBEACOPPbas. Progression-free (PFS) and overall survival (OS) were analyzed according to the Kaplan-Meier method. Cumulative incidences of secondary neoplasias (SN) were calculated and compared between groups using Pepe&Mori’s test. Type of SN, salvage therapies and causes of death were analyzed descriptively.
Results
The median FU was 120 and 98 months for patients in HD7 (n=627) and HD10 (n=1190) and 153 and 106 months for patients in HD8 (n=1064) and HD11 (n=1395), respectively. New FU data beyond the last evaluation was available for only <50% of patients and last information was obtained from population registries in 18-30%.In HD7, CMT was superior to EF-RT with 15-year PFS estimates of 72.8% vs. 52.2% and a hazard ratio (HR) of 0.45 (0.33-0.61). No significant differences were observed regarding OS (HR: 0.81 (0.56-1.18)) or the cumulative incidence of SN. In HD10, non-inferiority of 2xABVD + 20Gy IF-RT to more intensive treatment was confirmed with HRs of 1.0 (0.6-1.5) and 0.9 (0.5-1.6) and 10-year estimates of 87.2% and 94.1% for PFS and OS, respectively. No significant differences in SN were observed. In HD8, non-inferiority of IF- compared to EF-RT was confirmed with HRs of 0.98 (0.76-1.25) and 0.88 (0.66-1.16) for PFS and OS, respectively. We observed a non-significant trend towards more SN (15-year cumulative incidence 17.1% and 14.2%, respectively, p=0.3) and deaths from SN after EF-RT. In HD11, no difference in PFS was found with intensified chemotherapy compared to standard ABVD with either 30Gy IF-RT (HR: 1.1 (0.7-1.5)) or 20Gy IF-RT (HR: 0.8 (0.6-1.1). In contrast, there was a significant difference in 10-year PFS rates estimated at 77.6% versus 83.3% to the detriment of ABVD-treated patients who had received 20Gy instead of 30Gy IF-RT with a HR of 1.5 (1.0-2.1). After BEACOPPbas, 20Gy IF-RT was non-inferior to 30Gy IF-RT with a HR of 1.0 (0.7-1.5) for PFS. No differences in terms of OS or SN could be observed.
Conclusion
Long-term FU data of four large randomized GHSG phase III trials confirm the current risk-adapted therapeutic strategies in early-stage HL. Outcome in patients with early-stage favorable HL is optimal with CMT consisting of 2xABVD + 20Gy IF-RT with 10-year PFS and OS estimates of 87.2% and 94.1%, respectively. 10-year PFS and OS estimates in early-stage unfavorable HL treated with 4xABVD + 30Gy IF-RT leave room for improvement with 83.3% and 90.0%, respectively. Moderate intensification of chemotherapy does not improve efficacy outcome but might facilitate the reduction of IF-RT-dose. Continued FU is necessary to assess long-term effects of currently applied risk-adapted therapies.
Session topic: First-line treatment of Hodgkin Lymphoma
Keyword(s): Chemotherapy, Hodgkin's lymphoma, Long-term follow-up, Radiotherapy
Type: Oral Presentation
Presentation during EHA21: On Friday, June 10, 2016 from 11:45 - 12:00
Location: Hall A2
Background
Combined modality treatment (CMT) is currently considered as standard of care in patients with early-stage HL. During the years, a gradual toxicity reduction through balancing extent and intensity of radiotherapy (RT) and chemotherapy was achieved.
Aims
We evaluated long-term follow-up (FU) of pivotal trials, to ensure the applied therapies are safe and beneficial for our patients.
Methods
We analyzed updated FU data of 4299 patients who were treated for primary early-stage HL in previously published GHSG trials between 1993 and 2003. Patients with favorable disease were randomized in HD 7 to either CMT with 2xABVD or to 40Gy extended-field (EF)-RT only, and in HD10 to either 4x or 2xABVD and 20 or 30Gy involved-field (IF)-RT, respectively. Patients with unfavorable HL in HD8 had received either 30Gy IF- or extended-field (EF)-RT after 2xCOPP/ABVD and in HD11 either 20 or 30Gy IF-RT after 4xABVD or 4xBEACOPPbas. Progression-free (PFS) and overall survival (OS) were analyzed according to the Kaplan-Meier method. Cumulative incidences of secondary neoplasias (SN) were calculated and compared between groups using Pepe&Mori’s test. Type of SN, salvage therapies and causes of death were analyzed descriptively.
Results
The median FU was 120 and 98 months for patients in HD7 (n=627) and HD10 (n=1190) and 153 and 106 months for patients in HD8 (n=1064) and HD11 (n=1395), respectively. New FU data beyond the last evaluation was available for only <50% of patients and last information was obtained from population registries in 18-30%.In HD7, CMT was superior to EF-RT with 15-year PFS estimates of 72.8% vs. 52.2% and a hazard ratio (HR) of 0.45 (0.33-0.61). No significant differences were observed regarding OS (HR: 0.81 (0.56-1.18)) or the cumulative incidence of SN. In HD10, non-inferiority of 2xABVD + 20Gy IF-RT to more intensive treatment was confirmed with HRs of 1.0 (0.6-1.5) and 0.9 (0.5-1.6) and 10-year estimates of 87.2% and 94.1% for PFS and OS, respectively. No significant differences in SN were observed. In HD8, non-inferiority of IF- compared to EF-RT was confirmed with HRs of 0.98 (0.76-1.25) and 0.88 (0.66-1.16) for PFS and OS, respectively. We observed a non-significant trend towards more SN (15-year cumulative incidence 17.1% and 14.2%, respectively, p=0.3) and deaths from SN after EF-RT. In HD11, no difference in PFS was found with intensified chemotherapy compared to standard ABVD with either 30Gy IF-RT (HR: 1.1 (0.7-1.5)) or 20Gy IF-RT (HR: 0.8 (0.6-1.1). In contrast, there was a significant difference in 10-year PFS rates estimated at 77.6% versus 83.3% to the detriment of ABVD-treated patients who had received 20Gy instead of 30Gy IF-RT with a HR of 1.5 (1.0-2.1). After BEACOPPbas, 20Gy IF-RT was non-inferior to 30Gy IF-RT with a HR of 1.0 (0.7-1.5) for PFS. No differences in terms of OS or SN could be observed.
Conclusion
Long-term FU data of four large randomized GHSG phase III trials confirm the current risk-adapted therapeutic strategies in early-stage HL. Outcome in patients with early-stage favorable HL is optimal with CMT consisting of 2xABVD + 20Gy IF-RT with 10-year PFS and OS estimates of 87.2% and 94.1%, respectively. 10-year PFS and OS estimates in early-stage unfavorable HL treated with 4xABVD + 30Gy IF-RT leave room for improvement with 83.3% and 90.0%, respectively. Moderate intensification of chemotherapy does not improve efficacy outcome but might facilitate the reduction of IF-RT-dose. Continued FU is necessary to assess long-term effects of currently applied risk-adapted therapies.
Session topic: First-line treatment of Hodgkin Lymphoma
Keyword(s): Chemotherapy, Hodgkin's lymphoma, Long-term follow-up, Radiotherapy
Abstract: S106
Type: Oral Presentation
Presentation during EHA21: On Friday, June 10, 2016 from 11:45 - 12:00
Location: Hall A2
Background
Combined modality treatment (CMT) is currently considered as standard of care in patients with early-stage HL. During the years, a gradual toxicity reduction through balancing extent and intensity of radiotherapy (RT) and chemotherapy was achieved.
Aims
We evaluated long-term follow-up (FU) of pivotal trials, to ensure the applied therapies are safe and beneficial for our patients.
Methods
We analyzed updated FU data of 4299 patients who were treated for primary early-stage HL in previously published GHSG trials between 1993 and 2003. Patients with favorable disease were randomized in HD 7 to either CMT with 2xABVD or to 40Gy extended-field (EF)-RT only, and in HD10 to either 4x or 2xABVD and 20 or 30Gy involved-field (IF)-RT, respectively. Patients with unfavorable HL in HD8 had received either 30Gy IF- or extended-field (EF)-RT after 2xCOPP/ABVD and in HD11 either 20 or 30Gy IF-RT after 4xABVD or 4xBEACOPPbas. Progression-free (PFS) and overall survival (OS) were analyzed according to the Kaplan-Meier method. Cumulative incidences of secondary neoplasias (SN) were calculated and compared between groups using Pepe&Mori’s test. Type of SN, salvage therapies and causes of death were analyzed descriptively.
Results
The median FU was 120 and 98 months for patients in HD7 (n=627) and HD10 (n=1190) and 153 and 106 months for patients in HD8 (n=1064) and HD11 (n=1395), respectively. New FU data beyond the last evaluation was available for only <50% of patients and last information was obtained from population registries in 18-30%.In HD7, CMT was superior to EF-RT with 15-year PFS estimates of 72.8% vs. 52.2% and a hazard ratio (HR) of 0.45 (0.33-0.61). No significant differences were observed regarding OS (HR: 0.81 (0.56-1.18)) or the cumulative incidence of SN. In HD10, non-inferiority of 2xABVD + 20Gy IF-RT to more intensive treatment was confirmed with HRs of 1.0 (0.6-1.5) and 0.9 (0.5-1.6) and 10-year estimates of 87.2% and 94.1% for PFS and OS, respectively. No significant differences in SN were observed. In HD8, non-inferiority of IF- compared to EF-RT was confirmed with HRs of 0.98 (0.76-1.25) and 0.88 (0.66-1.16) for PFS and OS, respectively. We observed a non-significant trend towards more SN (15-year cumulative incidence 17.1% and 14.2%, respectively, p=0.3) and deaths from SN after EF-RT. In HD11, no difference in PFS was found with intensified chemotherapy compared to standard ABVD with either 30Gy IF-RT (HR: 1.1 (0.7-1.5)) or 20Gy IF-RT (HR: 0.8 (0.6-1.1). In contrast, there was a significant difference in 10-year PFS rates estimated at 77.6% versus 83.3% to the detriment of ABVD-treated patients who had received 20Gy instead of 30Gy IF-RT with a HR of 1.5 (1.0-2.1). After BEACOPPbas, 20Gy IF-RT was non-inferior to 30Gy IF-RT with a HR of 1.0 (0.7-1.5) for PFS. No differences in terms of OS or SN could be observed.
Conclusion
Long-term FU data of four large randomized GHSG phase III trials confirm the current risk-adapted therapeutic strategies in early-stage HL. Outcome in patients with early-stage favorable HL is optimal with CMT consisting of 2xABVD + 20Gy IF-RT with 10-year PFS and OS estimates of 87.2% and 94.1%, respectively. 10-year PFS and OS estimates in early-stage unfavorable HL treated with 4xABVD + 30Gy IF-RT leave room for improvement with 83.3% and 90.0%, respectively. Moderate intensification of chemotherapy does not improve efficacy outcome but might facilitate the reduction of IF-RT-dose. Continued FU is necessary to assess long-term effects of currently applied risk-adapted therapies.
Session topic: First-line treatment of Hodgkin Lymphoma
Keyword(s): Chemotherapy, Hodgkin's lymphoma, Long-term follow-up, Radiotherapy
Type: Oral Presentation
Presentation during EHA21: On Friday, June 10, 2016 from 11:45 - 12:00
Location: Hall A2
Background
Combined modality treatment (CMT) is currently considered as standard of care in patients with early-stage HL. During the years, a gradual toxicity reduction through balancing extent and intensity of radiotherapy (RT) and chemotherapy was achieved.
Aims
We evaluated long-term follow-up (FU) of pivotal trials, to ensure the applied therapies are safe and beneficial for our patients.
Methods
We analyzed updated FU data of 4299 patients who were treated for primary early-stage HL in previously published GHSG trials between 1993 and 2003. Patients with favorable disease were randomized in HD 7 to either CMT with 2xABVD or to 40Gy extended-field (EF)-RT only, and in HD10 to either 4x or 2xABVD and 20 or 30Gy involved-field (IF)-RT, respectively. Patients with unfavorable HL in HD8 had received either 30Gy IF- or extended-field (EF)-RT after 2xCOPP/ABVD and in HD11 either 20 or 30Gy IF-RT after 4xABVD or 4xBEACOPPbas. Progression-free (PFS) and overall survival (OS) were analyzed according to the Kaplan-Meier method. Cumulative incidences of secondary neoplasias (SN) were calculated and compared between groups using Pepe&Mori’s test. Type of SN, salvage therapies and causes of death were analyzed descriptively.
Results
The median FU was 120 and 98 months for patients in HD7 (n=627) and HD10 (n=1190) and 153 and 106 months for patients in HD8 (n=1064) and HD11 (n=1395), respectively. New FU data beyond the last evaluation was available for only <50% of patients and last information was obtained from population registries in 18-30%.In HD7, CMT was superior to EF-RT with 15-year PFS estimates of 72.8% vs. 52.2% and a hazard ratio (HR) of 0.45 (0.33-0.61). No significant differences were observed regarding OS (HR: 0.81 (0.56-1.18)) or the cumulative incidence of SN. In HD10, non-inferiority of 2xABVD + 20Gy IF-RT to more intensive treatment was confirmed with HRs of 1.0 (0.6-1.5) and 0.9 (0.5-1.6) and 10-year estimates of 87.2% and 94.1% for PFS and OS, respectively. No significant differences in SN were observed. In HD8, non-inferiority of IF- compared to EF-RT was confirmed with HRs of 0.98 (0.76-1.25) and 0.88 (0.66-1.16) for PFS and OS, respectively. We observed a non-significant trend towards more SN (15-year cumulative incidence 17.1% and 14.2%, respectively, p=0.3) and deaths from SN after EF-RT. In HD11, no difference in PFS was found with intensified chemotherapy compared to standard ABVD with either 30Gy IF-RT (HR: 1.1 (0.7-1.5)) or 20Gy IF-RT (HR: 0.8 (0.6-1.1). In contrast, there was a significant difference in 10-year PFS rates estimated at 77.6% versus 83.3% to the detriment of ABVD-treated patients who had received 20Gy instead of 30Gy IF-RT with a HR of 1.5 (1.0-2.1). After BEACOPPbas, 20Gy IF-RT was non-inferior to 30Gy IF-RT with a HR of 1.0 (0.7-1.5) for PFS. No differences in terms of OS or SN could be observed.
Conclusion
Long-term FU data of four large randomized GHSG phase III trials confirm the current risk-adapted therapeutic strategies in early-stage HL. Outcome in patients with early-stage favorable HL is optimal with CMT consisting of 2xABVD + 20Gy IF-RT with 10-year PFS and OS estimates of 87.2% and 94.1%, respectively. 10-year PFS and OS estimates in early-stage unfavorable HL treated with 4xABVD + 30Gy IF-RT leave room for improvement with 83.3% and 90.0%, respectively. Moderate intensification of chemotherapy does not improve efficacy outcome but might facilitate the reduction of IF-RT-dose. Continued FU is necessary to assess long-term effects of currently applied risk-adapted therapies.
Session topic: First-line treatment of Hodgkin Lymphoma
Keyword(s): Chemotherapy, Hodgkin's lymphoma, Long-term follow-up, Radiotherapy
{{ help_message }}
{{filter}}