Contributions
Abstract: EP769
Type: E-Poster Presentation
Session title: Hodgkin lymphoma - Clinical
Background
Classical hodgkin lymphoma (cHL) is a rare disease that commonly occurs in adolescents and young adults (AYAs), typically defined as 15 to 39 years. Given their young age at presentation, key factors in treatment selection include not only a high cure rate, but minimal long-term toxicities. Brentuximab vedotin (Adcetris®; A) is a CD30-directed ADC approved in combination with doxorubicin, vinblastine, and dacarbazine chemotherapy (A+AVD) for adults with previously untreated stage III/IV cHL based on results from the phase 3 ECHELON-1 trial. Recent 5-year data demonstrated a significantly improved PFS per investigator (INV) vs doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) (HR, 0.69; 95% CI, 0.54–0.9; P=0.003) (Straus 2020).
Aims
To describe key efficacy and safety results for AYA pts enrolled in ECHELON-1.
Methods
ECHELON-1 (N=1334) is a global, open-label, multicenter, randomized trial of pts with previously untreated stage III/IV cHL. A total of 771 AYAs (58%) received either A+AVD (n=396) or ABVD (n=375) with a PET scan after cycle 2 (PET2). An analysis of PFS (time from randomization to progression or death from any cause) per INV was conducted.
Results
These results refer to the AYA subset. After a median follow-up of 60.7 months (95% CI, 60.4-61.0), there was a 36% reduction in the risk of progression or death with A+AVD vs ABVD (HR 0.64; 95% CI, 0.45-0.92; P=0.013) with a 5-year PFS of 86.3% vs 79.4%, respectively, similar to the ITT population. The PFS benefit of A+AVD vs ABVD was independent of PET2 status; PET2 positivity (Deauville 4-5) was 6% and 8%, respectively.
On the A+AVD arm, 81 pts (20%) had at least one subsequent anticancer therapy (including radiotherapy) vs 96 pts (26%) on the ABVD arm; 26 pts (7%) received subsequent high dose chemotherapy and autologous stem cell transplant vs 32 pts (9%) on the A+AVD and ABVD arms, respectively.
Any-grade peripheral neuropathy (PN) occurred in 64% and 40% of pts on the A+AVD and ABVD arms, respectively. Resolution or improvement of PN occurred in 88-89% of pts on both arms. Ongoing PN was predominantly Grade 1 (62%) and Grade 2 (26%), with 8 pts (3% of the total cohort) on the A+AVD arm and one pt (<1%) on the ABVD arm reporting ongoing Grade 3 PN. Seven pts (1.8%) and 5 pts (1.4%) on the A+AVD and ABVD arms, respectively, reported a secondary malignancy.
Subsequent pregnancies were reported in female pts (44 A+AVD; 26 ABVD) and partners of male pts (31 A+AVD; 30 ABVD). No stillbirths were reported. All but one pt in each arm was <40.
Conclusion
Consistent with the ITT population, AYAs treated with A+AVD compared to ABVD had a durable PFS benefit at this significant 5-year milestone. No impact on the rate of secondary malignancies and a numerically greater number of pregnancies were observed, outcomes of interest to AYAs. Additionally, the majority of PN events improved or resolved over time. A+AVD should be considered a treatment option for AYAs with stage III/IV cHL.
Keyword(s): Adolescents, Hodgkin's lymphoma, Young adult
Abstract: EP769
Type: E-Poster Presentation
Session title: Hodgkin lymphoma - Clinical
Background
Classical hodgkin lymphoma (cHL) is a rare disease that commonly occurs in adolescents and young adults (AYAs), typically defined as 15 to 39 years. Given their young age at presentation, key factors in treatment selection include not only a high cure rate, but minimal long-term toxicities. Brentuximab vedotin (Adcetris®; A) is a CD30-directed ADC approved in combination with doxorubicin, vinblastine, and dacarbazine chemotherapy (A+AVD) for adults with previously untreated stage III/IV cHL based on results from the phase 3 ECHELON-1 trial. Recent 5-year data demonstrated a significantly improved PFS per investigator (INV) vs doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) (HR, 0.69; 95% CI, 0.54–0.9; P=0.003) (Straus 2020).
Aims
To describe key efficacy and safety results for AYA pts enrolled in ECHELON-1.
Methods
ECHELON-1 (N=1334) is a global, open-label, multicenter, randomized trial of pts with previously untreated stage III/IV cHL. A total of 771 AYAs (58%) received either A+AVD (n=396) or ABVD (n=375) with a PET scan after cycle 2 (PET2). An analysis of PFS (time from randomization to progression or death from any cause) per INV was conducted.
Results
These results refer to the AYA subset. After a median follow-up of 60.7 months (95% CI, 60.4-61.0), there was a 36% reduction in the risk of progression or death with A+AVD vs ABVD (HR 0.64; 95% CI, 0.45-0.92; P=0.013) with a 5-year PFS of 86.3% vs 79.4%, respectively, similar to the ITT population. The PFS benefit of A+AVD vs ABVD was independent of PET2 status; PET2 positivity (Deauville 4-5) was 6% and 8%, respectively.
On the A+AVD arm, 81 pts (20%) had at least one subsequent anticancer therapy (including radiotherapy) vs 96 pts (26%) on the ABVD arm; 26 pts (7%) received subsequent high dose chemotherapy and autologous stem cell transplant vs 32 pts (9%) on the A+AVD and ABVD arms, respectively.
Any-grade peripheral neuropathy (PN) occurred in 64% and 40% of pts on the A+AVD and ABVD arms, respectively. Resolution or improvement of PN occurred in 88-89% of pts on both arms. Ongoing PN was predominantly Grade 1 (62%) and Grade 2 (26%), with 8 pts (3% of the total cohort) on the A+AVD arm and one pt (<1%) on the ABVD arm reporting ongoing Grade 3 PN. Seven pts (1.8%) and 5 pts (1.4%) on the A+AVD and ABVD arms, respectively, reported a secondary malignancy.
Subsequent pregnancies were reported in female pts (44 A+AVD; 26 ABVD) and partners of male pts (31 A+AVD; 30 ABVD). No stillbirths were reported. All but one pt in each arm was <40.
Conclusion
Consistent with the ITT population, AYAs treated with A+AVD compared to ABVD had a durable PFS benefit at this significant 5-year milestone. No impact on the rate of secondary malignancies and a numerically greater number of pregnancies were observed, outcomes of interest to AYAs. Additionally, the majority of PN events improved or resolved over time. A+AVD should be considered a treatment option for AYAs with stage III/IV cHL.
Keyword(s): Adolescents, Hodgkin's lymphoma, Young adult