ASCO 2016 Abstract #7501: Higher Rate of ORR Achieved with Moga vs Investigator’s Choice for Treatment of R/R ATL
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.
This study was presented by Adrienne Alise Phillips who is Assistant Professor of Clinical Medicine at the New York-Presbyterian/Columbia University Medical Center in New York.
The primary outcome of this multicenter, open-label, randomized study (which started in June 2012) was overall response rate, supplemented by secondary outcome measures such as progression free survival, overall survival and quality of life. There was an estimated enrollment of 70 patients and inclusion criteria included, but was not limited to, ≥18 years of age, confirmed Adult T-cell Leukemia-Lymphoma (ATL) diagnosis (excluding smoldering type), and ECOG performance score of ≤2.
ATL treatment with mogamulizumab (moga), an anti-CCR4 monoclonal antibody, was compared to treatment with investigator’s choice (IC) treatment (pralatrexate or gemcitabine plus oxaliplatin or DHAP). ORR was higher in the moga arm than the IC arm by IR and by IA (23.4% vs8.3%, 34.0% vs 0%).
Background: ATL is a malignancy of T-cells infected with HTLV-1. Prognosis is poor and subtype related. There is no consensus treatment for R/R patients with aggressive ATL in whom median OS is < 3 months. Moga, a monoclonal antibody directed against CCR4 (expressed in >90% of ATL patients), is approved in Japan for the treatment of CCR4+ ATL, PTCL, and CTCL.
Methods: To evaluate moga outside of Japan, pts from sites in the USA, EU, and Latin America with aggressive R/R ATL (acute, lymphomatous, and chronic subtypes) were randomized 2:1 to treatment with moga, 1.0 mg/kg, given weekly for the first 4-week cycle and then biweekly, or to 1 of 3 investigator choice (IC) regimens (Gem/Ox, DHAP or pralatrexate). Due to the rarity of the disorder and lack of effective therapy, no power calculation was performed. Pts in the IC arm were permitted to cross-over to moga upon progression. The primary endpoint was objective response rate (ORR) based on modified Tsukasaki criteria. ORR was assessed by the treating investigator (IA) and in blinded fashion by independent review (IR).
Results: 71 pts were randomized (47 to moga, 24 to IC). Tissue/blood from 65/71 pts (91.5%) expressed CCR4. In the moga treated group, ORR was 23.4% (11/47) by IR and 34.0% (16/47) by IA; in the IC group, ORR was 2/24 (8.3%) by IR and 0/24 by IA. Confirmed ORR (maintained response after 1 month) for moga was 10.6% by IR and 14.9% by IA; there were no confirmed responses in the IC group. 18 IC pts crossed over to moga and 3 responded. Median duration of response for moga was 5.0 months by IR (range: 3.8–9.6 mos) and 1 pt had CR lasting >9 months. Survival data are not yet mature. The most frequently observed treatment-emergent, drug-related adverse events in the moga arm were infusion reactions (46.8%), rash/drug eruption (25.5%) and infections (14.9%).
Conclusions: This was the largest randomized clinical trial of R/R ATL thus far conducted. In patients with aggressive R/R ATL commonly used cytotoxic regimens provided limited therapeutic benefit whereas treatment with moga resulted in an ORR that supports its therapeutic potential in this setting. Clinical trial information: NCT01626664.
Phillips AA, et al. A prospective, multicenter, randomized study of anti-CCRA monoclonal antibody mogamulizumab (moga) vs investigator’s choice (IC) in the treatment of patients (pts) with relapsed/refractory (R/R) adult T-cell leukemia-lymphoma (ATL). J Clin Oncol 34, 2016 (suppl; abstr 7501).