Single agent bortezomib in the treatment of relapsed and refractory Hodgkin lymphoma: Cancer and leukemia Group B protocol 50206

Constitutive activation of nuclear factor-kappa B (NF-kappa B) has been described in patient-derived Reed - Sternberg cells and Hodgkin lymphoma ( HL) cell lines and contributes to the proliferation and survival of HL. Therapeutic inhibition of the proteasome with bortezomib may inhibit over-expression of nuclear NF-kappa B by preventing degradation of I kappa B, which sequesters NF-kappa B in the cytoplasm. To evaluate this hypothesis, the Cancer and Leukemia Group B (CALGB) conducted a multi-institutional phase II trial of single agent bortezomib in patients with relapsed or refractory classical HL. Thirty patients received bortezomib 1.3 mg/m(2) on days 1, 4, 8, 11 and every 21 days for a median of 2 cycles ( range, 1 - 8). Patients were heavily pre-treated with a median of four prior therapies, and 83% were previously transplanted. No responses were observed, 9 patients had stable disease, and 21 progressed. The median progression-free and overall survivals were 1.4 months [95% CI, ( 1.28, 1.91)] and 14.8 months [95% CI ( 11.2, 22.3)], respectively. Grade 3 - 4 adverse events, primarily thrombocytopenia, occurred in 15 patients. Therefore, although well tolerated, 1.3 mg/m(2) bortezomib administered biweekly has no single agent activity in relapsed/ refractory classical HL.