A phase I/II study of the pan Bcl-2 inhibitor obatoclax mesylate plus bortezomib for relapsed or refractory mantle cell lymphoma

André Goy, Francisco J. Hernandez-Ilzaliturri, Brad Kahl, Peggy Ford, Ewelina Protomastro, Mark Berger

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Obatoclax, a BH3 mimetic inhibitor of anti-apoptotic Bcl-2 proteins, demonstrates synergy with bortezomib in preclinical models of mantle cell lymphoma (MCL). This phase I/II study assessed obatoclax plus bortezomib in patients with relapsed/refractory MCL. Twenty-three patients received obatoclax 30 or 45 mg plus bortezomib 1.0 or 1.3 mg/m2, administered intravenously on days 1, 4, 8 and 11 of a 21-day cycle. In phase I, the combination was feasible at all doses. Obatoclax 45 mg plus bortezomib 1.3 mg/m2 was selected for phase II study. Common adverse events were somnolence (87%), fatigue (61%) and euphoric mood (57%), all primarily grade 1/2. Grade 3/4 events included thrombocytopenia (21%), anemia (13%) and fatigue (13%). Objective responses occurred in 4/13 (31%) evaluable patients (three complete and one partial response). Six patients (46%) had stable disease lasting ≥ 8 weeks. Obatoclax plus bortezomib was feasible, but the synergy demonstrated in preclinical models was not confirmed.

Original languageEnglish
Pages (from-to)2761-2768
Number of pages8
JournalLeukemia and Lymphoma
Volume55
Issue number12
DOIs
StatePublished - Dec 1 2014

Keywords

  • Bortezomib
  • Chemotherapeutic approaches
  • Drug resistance
  • Lymphoma and Hodgkin disease
  • Mantle cell
  • Obatoclax

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