Brentuximab vedotin plus chemotherapy for patients with previously untreated, Stage III or IV classical Hodgkin lymphoma: 5-year update of the phase 3 ECHELON-1 study (NCT01712490)
Radford, John A Dlugosz-Danecka, M. Connors, J. M. Illes, A. Picardi, M. Lech-Maranda, E. Feldman, T. Smolewski, P. Savage, K. J. Bartlett, N. L.
Radford, John A
Dlugosz-Danecka, M.
Connors, J. M.
Illes, A.
Picardi, M.
Lech-Maranda, E.
Feldman, T.
Smolewski, P.
Savage, K. J.
Bartlett, N. L.
Citations
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Abstract
Based on historical data, most relapses in classical
Hodgkin lymphoma (cHL) occur within 5 years of treatment (Radford
et al, BMJ 1997). In the ECHELON-1 study, treatment with
brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine
(A+AVD) significantly improved modified progression-free survival
(PFS) per independent review facility in patients (pts) with newly
diagnosed Stage III/IV cHL compared with doxorubicin, bleomycin,
vinblastine, and dacarbazine (ABVD) (Connors et al, NEJM 2018).
Durable PFS per investigator (INV) benefits with A+AVD vs ABVD
in the intent-to-treat (ITT) population, and across most key pt subgroups,
were seen after 3 and 4 years’ follow-up (Straus et al, Blood
2020; Bartlett et al, Blood 2019), improvements were seen, irrespective
of interim positron emission tomography (PET) scan status, disease
stage and baseline disease risk factor score. We report updated
efficacy and safety results after 5-years’ follow-up.
Pts with previously untreated Stage III or IV cHL were randomised
1:1 to receive up to 6 cycles of A+AVD (n = 664) or ABVD
(n = 670) intravenously on days 1 and 15 of a 28-day cycle. Patients
were required to have an interim PET scan after cycle 2 (PET2).
Analyses were performed after extended follow-up (cutoff date 18
September, 2020) to assess PFS per INV. Resolution and improvement (improvement by ≥1 grade from worst grade as of the
latest assessment) of peripheral neuropathy (PN) in pts with ongoing
symptoms at the end of treatment (EoT) were monitored throughout
the extended follow-up period. The rate of secondary malignancies,
and the incidence and outcomes of pregnancies among pts and their
partners were also assessed.
After a median follow-up of 60.9 months (95% confidence interval
[CI] 55.2–56.7), estimated 5-year PFS per INV rates were 82.2%
(95% CI 79.0–85.0) for A+AVD and 75.3% (95% CI 71.7–78.5) for
ABVD. PFS per INV favoured A+AVD over ABVD (hazard ratio
[HR] 0.681; 95% CI 0.534–0.867; P = 0.002) (Table). Estimated 5-
year PFS with A+AVD vs ABVD in the ITT population was 84.9% vs
78.9% in PET2-negative pts (HR 0.663; 95% CI 0.502–0.876;
P = 0.004) and 60.6% vs 45.9% in PET2-positive pts (HR 0.702;
95% CI 0.393–1.255; P = 0.229). In the A+AVD and ABVD arms,
85% and 86% of pts with treatment-emergent PN had complete resolution
or improvement of symptoms. Median time to complete resolution
of PN events ongoing at EoT was 34 weeks (range 0–262) in
the A+AVD arm and 16 weeks (range 0–267) in the ABVD arm;
median time to improvement was 49 weeks (range 8–270) and 12
weeks (range 2–70), respectively. In the A+AVD arm, 29% of pts
had ongoing PN with a maximum severity of grade 1 (17%), grade 2
(9%), grade 3 (3%) and grade 4 (<1%). In the ABVD arm, PN was
ongoing in 21% of pts; maximum severity was grade 1 (14%), 2
(6%) or 3 (1%). In total, 131 pregnancies were reported; the proportion
of ongoing pregnancies or live births in female pts was similar
in both arms (85% and 74% in the A+AVD and ABVD arms, respectively).
At 60.9 months’ median follow-up, sustained PFS benefit was
observed with A+AVD vs ABVD, which was independent of disease
stage and PET2 status. In addition, treatment adaptation by interim
PET2 status is not required for A+AVD and bleomycin exposure is
avoided. The durable and robust treatment benefit with A+AVD is
coupled with a manageable safety profile; these results suggest that
A+AVD is an attractive treatment option for all pts with previously
untreated Stage III or IV cHL.
Authors
Radford, John A
Dlugosz-Danecka, M.
Connors, J. M.
Illes, A.
Picardi, M.
Lech-Maranda, E.
Feldman, T.
Smolewski, P.
Savage, K. J.
Bartlett, N. L.
Walewski, J.
Ramchandren, R.
Zinzani, P. L.
Hutchings, M.
Munoz, J.
Kim, W. S.
Advani, R.
Ansell, S. M.
Younes, A.
Gallamini, A.
Liu, R.
Little, M.
Fenton, K.
Fanale, M
Straus, D. J.
Dlugosz-Danecka, M.
Connors, J. M.
Illes, A.
Picardi, M.
Lech-Maranda, E.
Feldman, T.
Smolewski, P.
Savage, K. J.
Bartlett, N. L.
Walewski, J.
Ramchandren, R.
Zinzani, P. L.
Hutchings, M.
Munoz, J.
Kim, W. S.
Advani, R.
Ansell, S. M.
Younes, A.
Gallamini, A.
Liu, R.
Little, M.
Fenton, K.
Fanale, M
Straus, D. J.
Description
Date
2021
Publisher
Collections
Keywords
Type
Meetings and Proceedings
Citation
Radford J, Dugosz-Danecka M, Connors JM, Savage KJ, Ills R, Picardi M, et al. Brentuximab vedotin plus chemotherapy for patients with previously untreated, Stage III or IV classical Hodgkin lymphoma: 5-year update of the phase 3 ECHELON-1 study (NCT01712490). British Journal of Haematology. 2021;193:145-7.