ECHELON-2 (NCT01777152), a randomized, double-blind, phase 3 study of brentuximab vedotin plus cyclophosphamide doxorubicin and prednisone versus cyclophosphamide, doxorubicin, vincristine and prednisone in previously untreated patients with CD30-positive peripheral T-cell lymphoma: 5-year results
Illidge, Timothy M Horwitz, S. M. O'Connor, O. A. Pro, B. Iyer, S. P. Advani, R. Bartlett, N. L. Christensen, J. H. Morschhauser, F. Domingo-Domenech, E.
Illidge, Timothy M
Horwitz, S. M.
O'Connor, O. A.
Pro, B.
Iyer, S. P.
Advani, R.
Bartlett, N. L.
Christensen, J. H.
Morschhauser, F.
Domingo-Domenech, E.
Citations
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Abstract
ECHELON-2, a phase 3, randomised, doubleblind,
double-dummy, placebo-controlled, active-comparator, multicentre
study, established the superiority of frontline brentuximab
vedotin + cyclophosphamide, doxorubicin and prednisone (A+CHP)
versus cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) for patients (pts) with previously untreated systemic
anaplastic large cell lymphoma (sALCL) or other CD30-expressing
peripheral T-cell lymphomas (PTCL) (Horwitz, Lancet 2019). At the
primary analysis, risk of progression-free survival (PFS) per blinded
independent central review (primary endpoint) and overall survival
(OS) events favoured A+CHP over CHOP. A+CHP was the first
treatment regimen to increase OS compared with CHOP in this population.
We report the 5-year data from ECHELON-2.
Adults with untreated CD30-positive PTCL (aiming to recruit
75 5% of pts with sALCL) were randomised 1:1 to receive 6–8
cycles of A+CHP or CHOP. Pts were stratified by histological subtype
and international prognostic index (IPI) score. We report PFS
per investigator (INV) and the following key secondary endpoints:
OS, PFS in sALCL, complete remission (CR) and objective response
rates (ORR) in re-treated pts. Brentuximab vedotin-based subsequent
therapies were allowed.
Of 452 pts enrolled, most had sALCL (n = 316 [70%]; 218 [48%]
anaplastic lymphoma kinase [ALK]-negative and 98 pts [22%] ALKpositive)
and most had advanced disease (27% Stage III, 53% Stage
IV; 78% IPI ≥2). At data cut-off, median follow-up was 47.6 months
for PFS and 66.8 months for OS. Hazard ratios (HRs) for PFS per
INV (0.70 [95% confidence interval [CI]: 0.53–0.91], P = 0.0077)
and OS (0.72 [95% CI: 0.53–0.99], P = 0.0424) favoured A+CHP
over CHOP. Median PFS was 62.3 months (95% CI: 42.0–not evaluable)
and 23.8 months (95% CI: 13.6–60.8) for A+CHP and CHOP,
respectively. Estimated 5-year PFS was 51.4% (95% CI: 42.8–59.4)
with A+CHP vs. 43.0% (95% CI: 35.8–50.0) with CHOP. Median
OS was not reached in either arm. Estimated 5-year OS was 70.1%
(95% CI: 63.3–75.9) for A+CHP vs. 61.0% (95% CI: 54.0–67.3) for
CHOP. PFS in prespecified subgroups was generally consistent with
overall PFS. In pts with sALCL, the HR for PFS (0.55 [95% CI:
0.39–0.79]) also favoured A+CHP over CHOP, with an estimated 5-
year PFS of 60.6% (95% CI: 49.5–69.9) for A+CHP vs. 48.4% (95%
CI: 39.6–56.7) for CHOP. A total of 29 pts (13%) in the A+CHP
arm (sALCL [n = 19], PTCL not otherwise specified [n = 5],
angioimmunoblastic T-cell lymphoma [n = 5]) and 54 pts (24%) in
the CHOP arm received subsequent systemic therapy with brentuximab
vedotin. In the A+CHP arm, median time to retreatment was
15.0 months (range, 3–64); 17 pts (ORR: 59%) had CR (n = 11) or
partial remission (n = 6) after retreatment with brentuximab vedotin
monotherapy (n = 25) or brentuximab vedotin-containing regimen
(n = 4). Treatment-emergent peripheral neuropathy (PN) occurred
in the A+CHP (n = 117) and CHOP arms (n = 124), of which, 72%
and 78% had resolved or improved in the A+CHP and CHOP arms,
respectively. In pts with ongoing events at last follow-up (A+CHP
[n = 47] vs. CHOP [n = 42]) PN was grade 1, 2 and 3 in 70% vs.
71%, 28% vs. 26% and 2% vs. 2%, respectively.
At 5 years’ follow-up, frontline A+CHP continued to provide
clinically meaningful improvements in PFS and OS versus CHOP,
including ongoing remission in 59% of re-treated pts with sALCL,
with a manageable safety profile, including continued resolution or
improvement of PN.
Authors
Illidge, Timothy M
Horwitz, S. M.
O'Connor, O. A.
Pro, B.
Iyer, S. P.
Advani, R.
Bartlett, N. L.
Christensen, J. H.
Morschhauser, F.
Domingo-Domenech, E.
Rossi, G.
Kim, W. S.
Feldman, T. A.
Menne, T.
Belada, D.
Illes, A.
Tobinai, K.
Tsukasaki, K.
Yeh, S. P.
Huttmann, A.
Savage, K. J.
Yuen, S.
Zinzani, P. L.
Miao, H.
Bunn, V.
Fenton, K.
Fanale, M. A.
Puhlmann, M
Trumper, L.
Horwitz, S. M.
O'Connor, O. A.
Pro, B.
Iyer, S. P.
Advani, R.
Bartlett, N. L.
Christensen, J. H.
Morschhauser, F.
Domingo-Domenech, E.
Rossi, G.
Kim, W. S.
Feldman, T. A.
Menne, T.
Belada, D.
Illes, A.
Tobinai, K.
Tsukasaki, K.
Yeh, S. P.
Huttmann, A.
Savage, K. J.
Yuen, S.
Zinzani, P. L.
Miao, H.
Bunn, V.
Fenton, K.
Fanale, M. A.
Puhlmann, M
Trumper, L.
Description
Date
2021
Publisher
Collections
Keywords
Type
Meetings and Proceedings
Citation
Illidge T, Horwitz SM, O'Connor OA, Pro B, Iyer SP, Advani R, et al. ECHELON-2 (NCT01777152), a randomized, double-blind, phase 3 study of brentuximab vedotin plus cyclophosphamide doxorubicin and prednisone versus cyclophosphamide, doxorubicin, vincristine and prednisone in previously untreated patients with CD30-positive peripheral T-cell lymphoma: 5-year results. British Journal of Haematology. 2021;193:38-40.