ASCO® 2016: 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 abstract (#7501was presented by Adrienne Alise Phillips, Assistant Professor of Clinical Medicine, New York-Presbyterian/Columbia University Medical Center in New York.

Adult T-cell Leukemia-Lymphoma (ATL) is a malignancy which arises from HTLV-1 infected T-cells. It carries a poor prognosis is poor and subtype related. Currently, there is no agreement on standard treatment for R/R patients with aggressive disease; whose median OS is less than 3 months.

Mogamulizumab (moga) is an anti-CCR4 monoclonal antibody; CCR4 is expressed in nearly all (>90%) of ATL cases. Moga holds Japanese approval for the treatment of CCR4+ ATL, PTCL, and CTCL.

The efficacy of moga was assessed outside of Japan in a multicenter, open-label, randomized study (NCT01626664), which enrolled patients with aggressive R/R ATL (acute, lymphomatous, and chronic subtypes) from sites in the USA, EU, and Latin America. ATL treatment with moga was compared to treatment with Investigator’s Choice (IC) treatment.

Beginning in June 2012, the primary outcome of this study was ORR, supplemented by secondary outcome measures such as PFS, OS, and QoL. Inclusion criteria included, but was not limited to, ≥18 years of age, confirmed ATL diagnosis (excluding smoldering type), and ECOG performance score of  ≤2.

Overall, 71 patients were randomized 2:1 to receive either moga 1.0mg/kg given weekly for the first 4-week cycle and then biweekly (n=47), or to 1 of 3 IC regimens (Gem/Ox, DHAP, or pralatrexate; n=24). Due to ATL being so rare, and lack of effective therapy, no power calculation was performed. Patients receiving IC therapy arm could cross-over to moga if they experienced disease progression.

  • With moga, ORR by Independent Review (IR) = 23.4% (11/47); ORR by Investigator (IA) = 34.0% (16/47)
  • With IC, ORR by IR = 8.3% (2/24); ORR by IA = 0%
  • With moga, confirmed ORR (maintained response after 1 month) by IR = 10.6%; by IA = 14.9% by IA
  • No confirmed responses found for the IC group
  • Of the 18 IC pts who crossed over to moga, 3 (17%) responded
  • With moga, median DoR by IA = 5.5 months; by IR = 5.0 months (range, 3.8–9.6 months); 1 patient had CR lasting >9 months
  • The most common treatment-emergent, drug-related AEs with moga were infusion reactions (46.8%), rash/drug eruption (25.5%), and infections (14.9%)

So far, this was the largest randomized clinical trial of R/R ATL. In patients with aggressive R/R ATL commonly used cytotoxic regimens resulted in little to no responses, whereas treatment with moga resulted in an ORR that supports its therapeutic potential in this setting.

Reference

1. 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).