Final Analysis of the Front-Line Phase III Randomized ACT-1 Trial in Younger Patients with Systemic Peripheral T-Cell Lymphoma Treated with CHOP Chemotherapy with or without Alemtuzumab and Consolidated By Autologous Hematopoietic Stem Cell Transplant

• Published in: Blood 2018-11, Vol.132 (Supplement 1), p.998-998
• Main Authors: d'Amore, Francesco, Leppä, Sirpa, Silva, Maria Gomes da, Relander, Thomas, Lauritzsen, Grete Fossum, Brown, Peter De Nully, Pezzutto, Antonio, Doorduijn, Jeanette K., Weidmann, Eckhart, van Gelder, Michel, Hoof, Achiel Van, Christiansen, Ilse, Fagerli, Unn Merete, Hagberg, Hans, Lugtenburg, P.J., Walewski, Jan, Wu, Ka Lung, Demuynck, Hilde Maria, Fijnheer, Rob, Christensen, Jacob H., Jankovská, Milada, Josefsson, Pär L., Kluin-Nelemans, Hanneke, Mariz, Jose Mario, Merup, Mats A., Noesslinger, Thomas, Van Den Neste, Eric, Zijlstra, Josée M, Hopfinger, Georg, Prochazka, VIT, Jantunen, Esa, Boudova, Ludmila, Cabecadas, Jose, Chott, Andreas, Delabie, Jan M.A., de Leval, Laurence, Diepstra, Arjan, Karjalainen-Lindsberg, Marja-Liisa, Noergaard, Peter, Rosenwald, Andreas, Rymkiewicz, Grzegorz, Sundström, Christer, Truemper, Lorenz, Wulf, Gerald, Chong, Lauren, Bouska, Alyssa, Smith, Lynette, Gisselbrecht, Christian, Ziepert, Marita, Loeffler, Markus, Liestol, Knut, Steidl, Christian, Gascoyne, Randy D., Scott, David W., Altmann, Bettina, Iqbal, Javeed, Chan, Wing C, Toldbod, Helle
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2018-99-110429

[§ share last authorship] Background: In 2000-2010, the first large prospective trials in peripheral T-cell lymphoma (PTCL) showed outcomes burdened by high failure rates during induction. Concurrently, trials with the anti-CD52 monoclonal antibody alemtuzumab (ALZ) yielded promising responses in PTCL while demonstrating the feasibility of combining ALZ with CHOP. Hence, the Nordic Lymphoma Group initiated the randomized ACT-1 trial to test, in younger patients (pts) (18-65yrs), the addition of ALZ to CHOP + autologous stem cell transplant (ASCT). Primary endpoint was the 3 years event-free survival (EFS). Here, we present the final analysis of the ACT-1 trial (ClinicalTrials.gov: NCT00646854). Patients and Methods: Overall, 136 pts were randomized (43% of planned sample size due to slow accrual), five did not receive study treatment, and 131 were analyzed (ALZ-CHOP: 65; CHOP: 66). Due to lack of tumoral CD52 expression, anaplastic large cell lymphomas (ALCL) were not included in the ACT-1 trial. An amendment tapering ALZ dose from 360 mg (30 mg on days 1+2 of each CHOP course) to 120 mg (30 mg on day 1 of CHOP courses 1-4) was introduced early on due to systemic fungal infections in 2 pts. Of the 65 pts treated with ALZ-CHOP, 4 received the pre- and 61 (94%) the post-amendment dose. Monitoring for CMV- and EBV-DNA and antimicrobial prophylaxis were mandatory. Results: The median observation time for the Full Analysis Set was 66 months and the median age 51 yrs. The ALZ-CHOP and CHOP cohorts were well balanced with regard to classical prognostic factors and histological subtypes (PTCL-NOS 58% vs 54%, AILT 21% vs 25%, other 21% vs 21%). Feasibility: Neither CHOP nor ALZ-CHOP pts experienced substantial treatment delay. ALZ exposure did not affect stem cell harvest nor hematopoietic recovery. Grade 4 leucopenia was more frequent in ALZ-CHOP pts (73% vs 35%; p=0.001), whereas the occurrence of grade 3-4 anemia and thrombocytopenia did not differ significantly. After ALZ dose amendment, the frequency of bacterial and fungal infections of grade ≥3 was similar in both treatment arms. ALZ treated pts had more viral events (22/57=42% vs 4/23=17%), mainly due to asymptomatic CMV reactivations. The ratio of serious adverse events per ALZ-CHOP treated patient dropped markedly (from 3.25 to 0.86, comparable with 0.46 for CHOP) after dose amendment. Additional toxicity was mild and similar in both arms. Treatment related mortality was 4% (5% vs 3%). Efficacy: Complete