A retrospective study analyzing activity of ofatumumab in blastic variant mantle cell lymphoma.

Abstract

e18500 Background: The blastic variant (BV) form of mantle cell lymphoma (MCL) is a rare and aggressive subtype of non-Hodgkin's lymphoma (NHL) for which no standard of care exists. Ofatumumab is a CD20-directed monoclonal antibody (mAb) FDA approved for the treatment of patients with CLL. We retrospectively studied relapsed BV of MCL in patients treated with regimens containing ofatumumab and previous or concurrent epigenetic therapy (cladribine (2-CdaA) and vorinostat). Methods: BV was confirmed by histopathological patterns, ki-67 proliferation index, immunophenotyping, and t(11;14) by FISH and/or cyclin D1 overexpression. The primary endpoint was overall response rate (ORR). Secondary endpoints included progression free survival and complete response. Correlative studies to support the hypothesis that epigenetic modulation of multiple genes in multiple pathways can potentiate the activity of mAbs were performed. Results: Ofatumumab administered to 5 Stage IV BV of MCL patients (Table). 3/5 patients had a radiological complete response, lasting 21.1, 13.4 and 12 months, The other 2 patients had partial response and are on the maintenance. Observed PFS in this cohort is a median 13 months (2.7-20.7). Correlative studies following epigenetic therapy found upregulation of the following genes by RT-PCR: NOXA1 (3/5 patients), CEBP1 (2/5) and EZH2 (2/5). Conclusions: Epigenetic drugs can augment the activity of mAbs. In this case, a more potent mAb improves response in MCL. Correlative studies to support the hypothesis that epigenetic modulation of multiple genes in multiple pathways can potentiate activity of mAbs. The combination of 2-CdA and vorinostat synergistically activates genes silenced by histone deacetylation, histone methylation and DNA methylation and enhances the activity of the mAb ofatumumab. [Table: see text]