Brentuximab vedotin plus chemotherapy for patients with previously untreated, stage III or IV Lclassical Hodgkin lymphoma: 5-year update of the phase 3 ECHELON-1 STUDY (NCT01712490)
Picardi, M. Straus, J. Dlugosz-Danecka, M. Connors, J. M. Illes, A. Lech-Maranda, E. Feldman, T. Smolewski, P. Savage, K. J. Bartlett, N. L.
Picardi, M.
Straus, J.
Dlugosz-Danecka, M.
Connors, J. M.
Illes, A.
Lech-Maranda, E.
Feldman, T.
Smolewski, P.
Savage, K. J.
Bartlett, N. L.
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Abstract
In the ECHELON-1 study, brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) significantly improved modified progression-free survival (PFS) per independent review in patients (pts) with
newly diagnosed Stage III/IV classical Hodgkin lymphoma (cHL) vsdoxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) (Connors,
NEJM 2018) and durable PFS per investigator (INV) benefits with
A+AVD vs ABVD were seen with extended follow-up (Bartlett, Blood
2019; Straus, Blood 2020). We report updated efficacy and safety data
after 5 years’ follow-up (cutoff date 18 Sep 2020). Pts with newly diagnosed Stage III/IV cHL were randomised 1:1 to up to 6 cycles of A+AVD
(n=664) or ABVD (n=670) on days 1 and 15 of a 28-day cycle. Interim
PET scan after cycle 2 (PET2) was mandated. Analyses were performed
for PFS per INV, peripheral neuropathy (PN) resolution and improvement (improvement by ≥1 grade [G] from worst G by latest assessment)
in pts with ongoing PN at end of treatment, rate of secondary malignancies, and pregnancy incidence and outcomes among pts and partners.
After 60.9 months median follow-up (95% confidence interval [CI]
55.2–56.7), estimated 5-year PFS per INV was 82.2% (95% CI 79.0–
85.0) for A+AVD and 75.3% (95% CI 71.7–78.5) for ABVD, favouring
A+AVD vs ABVD (hazard ratio [HR] 0.681; 95% CI 0.534–0.867;
p=0.002). Estimated 5-year PFS with A+AVDvsABVD in the intention
to treat population was 84.9% vs 78.9% in PET2– pts (HR 0.663; 95%
CI 0.502–0.876; p=0.004) and 60.6%vs 45.9% in PET2+ pts (HR 0.702;
95% CI 0.393–1.255; p=0.229). In A+AVD and ABVD arms, 85% and
86% of pts with treatment-emergent PN had complete resolution or improvement of symptoms. In A+AVD and ABVD arms, PN was ongoing
in 29% and 21% of pts, respectively, most of which were G1–2. In total,
131 pregnancies were reported; the proportion of ongoing pregnancies
or live births in female pts was similar in both arms (A+AVD arm 85%,
ABVD arm 74%). With 5 years’ follow-up, sustained PFS benefit was
observed with A+AVD vs ABVD that 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. As most
historical cHL relapses occur within the first 5 years (Radford, BMJ
1997), the durable and robust treatment benefit and manageable safety
profile of A+AVD in ECHELON-1, suggest that A+AVD is an attractive
treatment option for all pts with previously untreated Stage III/IV cHL.
Authors
Picardi, M.
Straus, J.
Dlugosz-Danecka, M.
Connors, J. M.
Illes, A.
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.
Gallamini, A.
Liu, R.
Little, M.
Fenton, K.
Fanale, M.
Radford, John A
Straus, J.
Dlugosz-Danecka, M.
Connors, J. M.
Illes, A.
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.
Gallamini, A.
Liu, R.
Little, M.
Fenton, K.
Fanale, M.
Radford, John A
Description
Date
2021
Publisher
Collections
Keywords
Type
Meetings and Proceedings
Citation
Picardi M, Straus J, Dlugosz-Danecka M, Connors JM, Illes A, Lech-Maranda E, 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). Haematologica. 2021;106(10):44-.