Role of stem cell transplant in CD30+ PTCL following frontline brentuximab vedotin plus CHP or CHOP in ECHELON-2

Abstract

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of aggressive non-Hodgkin lymphomas, the majority of which have high relapse rates following standard therapy. Despite use of consolidative stem cell transplant (SCT) following frontline therapy, there remains no consensus on its utility. The double-blind randomized phase 3 ECHELON-2 study (#NCT01777152; clinicaltrials.gov) demonstrated improved progression-free survival (PFS) and overall survival with frontline brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (A+CHP). Herein, we conducted an exploratory subgroups analysis of the impact of consolidative SCT on PFS in patients with previously untreated CD30+ PTCL (ALK- anaplastic large cell lymphoma [ALCL] and non-ALCL) who were in complete response (CR) after frontline treatment with A+CHP or cyclophosphamide, doxorubicin, vincristine, and prednisone. Median PFS follow-up was 47.57 months. The PFS hazard ratio was 0.36, equating to a 64% reduction in the risk of a PFS event in patients who underwent SCT. The median PFS in patients who underwent SCT was not reached, vs 55.66 months in patients who did not undergo SCT. PFS results favored the use of SCT in both ALK- ALCL and non-ALCL subgroups. These data support the consideration of consolidative SCT in patients with CD30+PTCL who achieve CR following treatment with A+CHP.

Conflict of interest statement

Conflict-of-interest disclosure: S.M.H. has consulted, received honorarium from, or participated in advisory boards for Acrotech Biopharma, C4 Therapeutics, Janssen, Kura Oncology, Kyowa Hakko Kirin, Myeloid Therapeutics, ONO Pharmaceuticals, Seagen Inc., Takeda, Trillium Therapeutics, and Vividion Therapeutics and has received research support for clinical trials from ADC Therapeutics, Affimed, Aileron, Celgene, Daiichi Sankyo, Forty Seven Inc., Kyowa Hakko Kirin, Millennium/Takeda, Portola Pharmaceuticals, Seagen Inc., Trillium Therapeutics, and Verastem. T.I. serves on the speakers bureau for Takeda. S.I. receives research funding from Arog, Bristol-Myers Squibb, Genentech/Roche, Incyte, and Seagen Inc. R.A. consults for Astra Zeneca, Bayer Healthcare Pharmaceuticals, Cell Medica, Celgene, Genentech/Roche, Gilead, KitePharma, Kyowa, Portola Pharmaceuticals, Sanofi, Seagen Inc., and Takeda. J.H.A. receives research funding from Seagen Inc. F.M. serves on the board of directors or advisory committees at Abbivie, Celgene, Epizyme, Gilead; receives honoraria from Janssen; consultants with and receives honoraria from and serves on the board of directors at Roche; and consultants for Servier. E.D.-D. consults for and receives travel, accommodation, expense, and research funding from Takeda; received travel and research funding from Bristol-Myers Squibb; receives travel, accommodation, and expense funding from Roche and Janssen; and receives research funding from Seagen Inc. G.R. consults for and receives honoraria from Daiichi Sankyo; serves on the advisory board for Roche, Janssen, Celgene, Amgen, Novartis, and Astellas; serves on the advisory board and receives travel expense funding from Gilead and Alexion; receives honoraria from and serves on the advisory board for Sandoz; receives honoraria from Incyte, Sanofi, Bristol-Myers Squibb, Mundipharma, and Novartis; is a member of the board of directors or advisory committees at Abbvie, Jazz, Pfizer, and Teva; receives research funding from Seagen Inc.; and travel expenses from Alexion. K.T. receives honoraria from Bristol-Myers Squibb, Eisai, and Solasia; consults and receives honoraria from Celgene, Chugai Pharma, Daiichi Sankyo, HUYA Bioscience, Kyowa Kirin, Mundipharma, Ono Pharma, Takeda, Yakult, and Zenyaku Kogyo; and consults for SymBio. A.R.S. receives research funding from Seagen Inc. K.J.S. consults and receives honoraria from Seagen Inc., Bristol Myers Squibb, Merck, Janssen, Kyowa; is a member of the advisory committees at Bristol-Myers Squibb, Steering Committee Beigene, and DSMC Regeneron; and receives institutional research funding from Roche and BMS. P.L.Z. receives honoraria and is a member of the board of directors or advisory committees and speakers bureau at Merck, AbbVie, Takeda, Incyte, Kirin Kyowa, and ADC Therapeutics; consults for, receives honoraria from, and is a member of the board of directors or advisory committees and speakers bureau at BMS, Gilead, Roche, Servier, EUSA Pharma, Verastem, Celltrion, Janssen-Cilag, Sandoz, MSD, Immune Design, and Celgene; receives honoraria from and is on the speakers bureau at TG Therapeutics Inc.; consults for and is a member of the board of directors or advisory committees at Sanofi; consults for and is a member of the board of directors or advisory committees, receives research funding, and is on the speakers bureau at Portola; consults for and is on the speakers bureau at EUSA Pharma and Kyowa Kirin; and is a member of the board of directors or advisory committees and speakers bureau at Immune Design. H.M. is a current equity holder at Takeda. V.B. receives research funding from Seagen Inc. and is currently employed at Takeda. K.F. is an employee of an has an equity interest in Seagen Inc. M.A.F. is an employee of and has an equity interest in Seagen Inc. M.P. is an employee of and has an equity interest in Seagen Inc. L.T. consults for Janssen and Nordic Nanovector; receives research funding from Mundipharma, Roche, and Seagen Inc.; and consults for and receives research funding from Takeda Europe. O.A. serves on the advisory board at Kyowa Kirin and Seagen Inc. and receives research funding from Seagen Inc. C.S. receives research funding from Seagen Inc. M.T. receives research funding from Seagen Inc. The remaining authors declare no competing financial interests.

The current affiliation for A.S. is Seagen Inc., Bothell, WA.

© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

Figures

Figure 1.

Patient flow diagram for ECHELON-2 exploratory analysis: A+CHP arm. There were no significant differences (P = .49) in the baseline international prognostic index score distribution between patients who received SCT and patients who did not receive SCT. Note that 12 transplanted patients were excluded from the analysis (4 patients with ALK+; 8 did not have CR at EOT [6 PR, 1 SD, and 1 not evaluable]), for a total analysis population of n = 38. Consistent criteria were applied per protocol for response assessments. PR, partial response.

Figure 2.

PFS by consolidative SCT: A+CHP arm. (A) PFS by consolidative SCT after A+CHP in patients with CR at EOT: ALK− sALCL and Non-sALCL. (B) PFS by consolidative SCT after A+CHP in patients with CR at EOT: ALK− sALCL. (C) PFS by consolidative SCT after A+CHP in patients with CR at EOT: Non-sALCL. ITT, intention to transplant.