CHICAGO — When added to the CHOP regimen, alemtuzumab increases remission rates in elderly patients with peripheral T cell lymphoma, final analysis of the international ACT-2 phase 3 trial presented at the American Society of Clinical Oncology (ASCO) 2016 Annual Meeting has shown.1
However, the addition of alemtuzumab did not improve event-free survival, progression-free survival, or overall survival, said Lorenz H. Trümper, MD, Georg-August University, Goettingen, Germany, presenting on behalf of the Deutsche Studiengruppe Hochmaligne Lymphome DSHNHL.
To date, standard treatment for peripheral T cell lymphoma remains unsatisfactory, due to high rates of early disease progression.
Between October 2007 and September 2013, the study randomly assigned 116 patients from 52 centers to receive either 6 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone; n = 58) or CHOP plus alemtuzumab, a monoclonal anti-CD52 antibody (n = 58), at 14-day intervals with G-CSF support. Patients received a total of alemtuzumab 360 mg until patient 39, when it was decreased to 120 mg.
“The protocol demanded stringent CMV/EBV monitoring and anti-infective prophylaxis,” he said. The study was powered to detect a 15% increase in event-free survival when alemtuzumab was added to CHOP.
Median patient age was 69 years (range, 60 to 80 years) and 58% were male. A total of 41% had angioimmunoblastic T cell lymphoma; 39%, peripheral T cell lymphoma not otherwise specified; 6%, anaplastic large cell lymphoma; and 14% had other subtypes.
Treatment as planned was administered in 79% of patients in the CHOP arm and 57% of the CHOP plus alemtuzumab arm. Grade 3/4 hematotoxicity was more frequent in the CHOP plus alemtuzumab arm: leukocytopenia grade 4 was 70% vs 54% in the CHOP arm, and thrombocytopenia grade 3/4 was 19% vs 13%, respectively. Infections were also higher in the CHOP plus alemtuzumab arm; 19 of 38 patients had viral infections (14 of which were CMV); 4 had fungal infections (including 1 Aspergillus); and 12 had bacterial infections, compared with no viral infections, 1 fungal infection, and 10 bacterial infections in the CHOP arm.
Complete remissions were achieved in 43% (95% CI, 30-57) of patients in the CHOP arm and 60% (95% CI, 47-73) in the CHOP plus alemtuzumab arm. Progressive disease occurred in 22% of patients in the CHOP arm and 16% in the CHOP plus alemtuzumab arm.
At 3 years, no significant differences were observed for event-free survival (23% for the CHOP arm and 26% for the CHOP plus alemtuzumab arm), progression-free survival (29% vs 26%), and overall survival (56% vs 38%).
Multivariate analysis for overall survival showed the most prominent risk factors to be bulky disease, defined as 7.5 cm (RR, 4.5; 95% CI, 2.2-9.2; P < .001), male gender (RR, 2.4; 95% CI, 1.4-4.4; P = .003), and ECOG > 1 (RR 2.0; 95% CI, 1.1-3.9; P = .034).
These data “provide a valuable dataset for planning of future trials,” he said. “Novel agents for the treatment of elderly patients with peripheral T cell lymphoma remains an urgent medical need,” Dr. Trümper concluded.
1. Trümper LH, Wulf G, Ziepert M, 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. Oral presentation at: ASCO 2016 Annual Meeting; June 3-7, 2016; Chicago, IL.