A phase II study of bortezomib in relapsed Hodgkin lymphoma: Preliminary results of CALGB 50206.

7576 Background: Constitutive NF-κB activation has been described in both Hodgkin lymphoma (HL) cell lines and patient-derived Reed-Sternberg cells. In vitro, therapeutic targeting of NF-κB with proteasome inhibitors like bortezomib leads to apoptosis of HL cell lines, providing a rationale for clinical trials with this agent. METHODS: From 3/15/2004 until 2/23/2005, the CALGB conducted a phase II trial of bortezomib in patients (pts) with relapsed and refractory classical HL to assess response rate and toxicity. Eligibility requirements included at least one prior systemic therapy, measurable disease, absolute neutrophil count ≥ 750/μL, platelets ≥ 75,000/μl, and creatinine ≤ 2.5 mg/dl. Pts able to undergo a stem cell transplant with curative intent or with pre-existing sensory neuropathy ≥ grade 2 were not eligible. Bortezomib was administered at 1.3 mg/m(2) days 1, 4, 8, and 11 every 21 days for 2-8 cycles, or until disease progression. RESULTS: 30 pts received a median of 2 cycles (range, 1-8). For 25 pts with available data, 80% had stage IV disease with a median of 4 prior therapies (range 2-8, 92% with prior stem cell transplant). For 29 pts with complete response data, 2 pts were not evaluable due to adverse events (bleeding gastric ulcer and grade 4 dyspnea) during cycle 1 leading to a discontinuation of therapy prior to restaging. In the remaining 27, no responses were observed [95% CI (0.0, 0.13)]; 18 pts progressed, and 9 pts had stable disease. Median follow-up is 4.4 (range, 0.6 -16.4) months. The median progression-free and overall survival times are 1.4 [95% CI (1.3, 2.8)] and 11.6 months [95% CI (6.6, ongoing)], respectively. Toxicity data are available for 26 pts. Grade 3-4 events included thrombocytopenia (27%), lymphopenia (8%), dyspnea (8%), anemia (4%), diarrhea (4%), hypotension (4%), rash (4%), and hyperbilirubinemia (4%). Both instances of grade 3-4 dyspnea occurred in pts with disease progression in the lung. 27% developed grade 2 sensory or motor neuropathy. CONCLUSIONS: Although well-tolerated, bortezomib has no single agent efficacy in relapsed classical HL at the current dose and schedule. No significant financial relationships to disclose.

Duke Scholars

Author Donna Niedzwiecki Biostatistics & Bioinformatics, Division of Biostatistics