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ASCO 2016 Abstract #7500: ACT-2 Phase III International Trial Final Results – Improved CR with A-CHOP Compared to CHOP Alone in Elderly Patients with pTNHL

This ASCO 2016 oral abstract presentation took place on Sunday June 5, 9:45am–12:45pm, during the ‘Hematologic Malignancies-Lymphoma and Chronic Lymphocytic Leukemia’ session. This session was chaired by Pr Gilles Salles, Head of the Hematology Department in South Lyon hospitals, Lyon, France.

The abstract was presented by Prof. Lorenz H Trumper of the Department of Hematology and Oncology, University of Göttingen, Georg-August-Universität, Göttingen, Germany.

This interventional, randomized, open label, phase III study, which began in February 2008, had a primary outcome measure of event free survival and an estimated enrolment of 274. Inclusion criteria included patients aged between 61 and 80 years, all risk groups of Peripheral T-Cell Lymphoma, and an ECOG performance status of 0–2.

A higher rate of complete remission was achieved in the alemtuzumab (A)-CHOP arm than in the CHOP arm (60% vs 43%), however more grade ≥ 3 infections occurred in the A-CHOP arm than in the CHOP arm, with rates of 40% and 21% respectively.

Abstract 7500

Background: Standard treatment in pTNHL pts is unsatisfactory due to a high rate of early progression. Alemtuzumab (A), a monoclonal anti-CD52 antibody, has demonstrated efficacy in relapsed pTNHL pts, and phase II trials have shown feasibility of concomitant A+CHOP application. We report the final analysis of the international ACT-2 phase III randomized trial in elderly pts comparing standard CHOP to A-CHOP.

Methods: Between 2007 and 2013, 116 pts from 52 centers were randomized to receive either 6 cycles of CHOP or A-CHOP at 14-day intervals with G-CSF support. Pts were to receive a total of 360 mgs A (until pt 39) or 120 mg. The protocol demanded stringent CMV / EBV monitoring and anti-infective prophylaxis. The study was powered to detect a 15% increase in EFS with the addition of A to CHOP.

Results: 116 pts (median age 69 yrs, 58% male) were randomized (58/58). Histologies were 41% AITL, 39% pTNHL NOS, 6% ALCL, 14% other subtypes. Complete treatment as planned was applied in 79% (CHOP) resp 57% (A-CHOP) of pts. Hematotoxicity grade 3/4 was more frequent in A-CHOP (leukocytopenia 4: 70 vs 54%, thrombocytopenia 3/4: 19 vs 13%) resulting in more grade ≥ 3 infections (40 vs. 21%). Complete remissions were achieved in 43% of CHOP and 60% of A-CHOP pts. EFS, PFS and OS at 3 yrs showed no significant differences, also in multivariate analyses (hazard ratios HR 0.7 – 1.4) adjusted for strata and gender. Bulky disease (HR 2.2), extranodal disease > 1 (HR 2.3) and male gender (HR 2.5) were the most prominent risk factors for EFS.

Conclusions: A added to CHOP in elderly pTNHL pts increases response rates. Survival was not improved mostly due to treatment related toxicity. Risk factor and biomarker analysis including data from the ACT-1 trial are ongoing and may identify pts who benefit from A, as may improvement of antiviral strategies. Identifying new agents that improve response without undue toxicity remains an unmet medical need. Clinical trial information: NCT00725231.

 

CHOP

A-CHOP

all pts

CR

43 (30;57)

60 (47; 73)

52 (42; 61)

Relapse

48 (28; 69)

43 (26; 61)

45 (32; 58)

EFS

23 (12; 35)

26 (13; 38)

24 (16; 33)

PFS

29 (17; 41)

26 (14; 38)

28 (19; 36)

OS

56 (43; 69)

38 (24; 51)

48 (38; 57)

Results in % with 95% confidence intervals.

Reference

Lorenz H, et al. Alemtuzumab added to CHOP for treatment of peripheral T-cell lymphoma (pTNHL) of the elderly: final results of 116 patients treated in the international ACT-2 phase III trial. J Clin Oncol 34, 2016 (suppl; abstr 7500).