Brentuximab vedotin with chemotherapy for patients with previously untreated Stage III/IV classical hodgkin lymphoma: 5-Year update of the ECHELON-1 study
Ramchandren, R. Dlugosz-Danecka, M. Connors, J. M. Radford, John A Illes, A. Picardi, M. Lech-Maranda, E. Feldman, T. Smolewski, P. Savage, K. J.
Ramchandren, R.
Dlugosz-Danecka, M.
Connors, J. M.
Radford, John A
Illes, A.
Picardi, M.
Lech-Maranda, E.
Feldman, T.
Smolewski, P.
Savage, K. J.
Citations
Altmetric:
Abstract
Objective: Historically, nearly all relapses in classical Hodgkin
lymphoma (cHL) occur within the fi rst 5 years of treatment
(Radford et al., BMJ 1997;314:346). In ECHELON-1,
brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine
(A+AVD) signifi cantly improved modifi ed progression-free survival
(PFS) versus doxorubicin, bleomycin, vinblastine, and dacarbazine
(ABVD) in patients with stage III/IV cHL (Connors et al., NEJM
2018;378:331). We report updated effi cacy and safety results; median
follow-up was 60.9 months. Design: This phase 3, open-label study
(NCT01712490) randomized patients with previously untreated
stage III/IV cHL to receive 6 cycles of A+AVD or ABVD. Patients
underwent an interim positron emission tomography scan after
cycle 2 (PET2). An exploratory analysis of PFS per investigator was
conducted. Results: There were 664 and 670 patients randomized
to receive A+AVD and ABVD, respectively. 64%, 62%, and 58% of
patients had stage IV disease, extranodal involvement at diagnosis,
and B symptoms, respectively. Five-year PFS was 82.2% (95%
confi dence interval [CI]: 79.0–85.0) with A+AVD and 75.3% (95%
CI: 71.7–78.5) with ABVD. Overall, PFS favored A+AVD (hazard
ratio [HR]: 0.681; 95% CI: 0.534–0.867; P=0.002). PFS benefi ts
were observed regardless of PET2 status and International Prognostic
Score. Estimated 5-year PFS with A+AVD versus ABVD was 84.9%
versus 78.9% in PET2-negative patients (HR: 0.663; 95% CI:
0.502–0.876; P=0.004), and 60.6% versus 45.9% in PET2-positive
patients (HR: 0.702; 95% CI: 0.393–1.255; P=0.229). Treatment-emergent peripheral neuropathy (PN) resolved or improved in 85%
(n=375/443) and 86% (n=245/286) of the patients with PN on
A+AVD and ABVD, respectively. Secondary malignancies occurred
in 19 and 29 patients with A+AVD and ABVD, respectively. A
total of 131 female patients or partners of male patients reported
a pregnancy; both arms showed similar proportions of ongoing
pregnancies or live births. Conclusions: At 5 years, A+AVD still
demonstrates clinically meaningful improvement in PFS versus
ABVD, independent of PET2 status, with a manageable safety
profi le, including resolution or improvement of PN. The PFS
benefi t observed with A+AVD at this important milestone suggests
that A+AVD is an attractive treatment option for all patients with
previously untreated stage III/IV cHL
Authors
Ramchandren, R.
Dlugosz-Danecka, M.
Connors, J. M.
Radford, John A
Illes, A.
Picardi, M.
Lech-Maranda, E.
Feldman, T.
Smolewski, P.
Savage, K. J.
Bartlett, N. L.
Walewski, J.
Zinzani, P. L.
Hutchings, M.
Munoz, J.
Kim, W. S.
Advani, R.
Ansell, S. M.
Gallamini, A.
Alekseev, S.
Lee, H. J.
Liu, R.
Little, M.
Fenton, K.
Fanale, M.
Straus, D. J.
Dlugosz-Danecka, M.
Connors, J. M.
Radford, John A
Illes, A.
Picardi, M.
Lech-Maranda, E.
Feldman, T.
Smolewski, P.
Savage, K. J.
Bartlett, N. L.
Walewski, J.
Zinzani, P. L.
Hutchings, M.
Munoz, J.
Kim, W. S.
Advani, R.
Ansell, S. M.
Gallamini, A.
Alekseev, S.
Lee, H. J.
Liu, R.
Little, M.
Fenton, K.
Fanale, M.
Straus, D. J.
Description
Date
2021
Publisher
Collections
Keywords
Type
Other
Citation
Ramchandren R, Dlugosz-Danecka M, Connors JM, Radford J, Illes A, Picardi M, et al. Brentuximab Vedotin with Chemotherapy for Patients with Previously Untreated Stage III/IV Classical Hodgkin Lymphoma: 5-Year Update of the ECHELON-1 Study. Clinical Lymphoma Myeloma & Leukemia. 2021;21:S371-S.