Older patients (aged ≥60 years) with previously untreated advanced-stage classical Hodgkin lymphoma: a detailed analysis from the phase III ECHELON-1 study

Andrew M Evens, Joseph M Connors, Anas Younes, Stephen M Ansell, Won Seog Kim, John Radford, Tatyana Feldman, Joseph Tuscano, Kerry J Savage, Yasuhiro Oki, Andrew Grigg, Christopher Pocock, Monika Dlugosz-Danecka, Keenan Fenton, Andres Forero-Torres, Rachael Liu, Hina Jolin, Ashish Gautam, Andrea Gallamini, Andrew M Evens, Joseph M Connors, Anas Younes, Stephen M Ansell, Won Seog Kim, John Radford, Tatyana Feldman, Joseph Tuscano, Kerry J Savage, Yasuhiro Oki, Andrew Grigg, Christopher Pocock, Monika Dlugosz-Danecka, Keenan Fenton, Andres Forero-Torres, Rachael Liu, Hina Jolin, Ashish Gautam, Andrea Gallamini

Abstract

Effective and tolerable treatments are needed for older patients with classical Hodgkin lymphoma. We report results for older patients with classical Hodgkin lymphoma treated in the large phase III ECHELON-1 study of frontline brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A+AVD) versus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). Modified progression-free survival per independent review facility for older versus younger patients (aged ≥60 vs. <60 years) was a pre-specified subgroup analysis; as the ECHELON- 1 study was not powered for these analyses, reported P-values are descriptive. Of 1,334 enrolled patients, 186 (14%) were aged ≥60 years (A+AVD: n=84, ABVD: n=102); results below refer to this age group. Modified progression-free survival per independent review facility was similar in the two arms at 24 months (A+AVD: 70.3% [95% confidence interval (CI): 58.4-79.4], ABVD: 71.4% [95% CI: 60.5-79.8], hazard ratio (HR)=1.00 [95% CI: 0.58-1.72], P=0.993). After a median follow-up of 60.9 months, 5-year progression-free survival per investigator was 67.1% with A+AVD versus 61.6% with ABVD (HR=0.820 [95% CI: 0.494-1.362], P=0.443). Comparing A+AVD versus ABVD, grade 3/4 peripheral neuropathy occurred in 18% versus 3%; any-grade febrile neutropenia in 37% versus 17%; and any-grade pulmonary toxicity in 2% versus 13%, respectively, with three (3%) pulmonary toxicity-related deaths in patients receiving ABVD (none in those receiving A+AVD). Altogether, A+AVD showed overall similar efficacy to ABVD with survival rates in both arms comparing favorably to those of prior series in older patients with advanced-stage classical Hodgkin lymphoma. Compared to ABVD, A+AVD was associated with higher rates of neuropathy and neutropenia, but lower rates of pulmonary-related toxicity. Trials registered at ClinicalTrials.gov identifiers: NCT01712490; EudraCT number: 2011-005450-60.

Figures

Figure 1.
Figure 1.
Progression-free survival in patients aged ≥60 years. (A) Modified progression-free survival (PFS) per independent review facility after a median follow-up of 25 months. (B) PFS per investigator after a median follow-up of 60.9 months. A+AVD: brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine; ABVD: doxorubicin, bleomycin, vinblastine, and dacarbazine; CI: confidence interval; HR: hazard ratio; INV: investigator; IRF: independent review facility.

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