Abstract

Background: The proteasome inhibitor bortezomib induces cell cycle arrest and apoptosis of Hodgkin lymphoma (HL) cells. We have demonstrated that bortezomib’s single agent efficacy was limited in heavily pretreated HL patients. However, preclinical work has shown that bortezomib may synergize with chemotherapy. Thus, we evaluated the combination of bortezomib plus ICE chemotherapy in patients with relapsed/refractory HL.

Methods: Eligibility:

  1. Relapsed/refractory classical HL,

  2. Only 1 prior chemotherapy regimen,

  3. Prior treatment with anthracycline-containing regimen,

  4. No prior ASCT.

Regimen: ICE (Moskowitz, C et al 2001). Bortezomib on D1 and D4 at dose levels of 0 = 1 mg/m2, 1 = 1.3 mg/m2, 2 = 1.5 mg/m2. Neulasta given on D5. Cycles were repeated on D14 if platelet count is ≥ 100,000/mm3 and ANC is ≥ 1,000/mm3. After 3 cycles CTs and PET/CT were performed to evaluate response. Hematologic DLT was defined as grade 4 thrombocytopenia or neutropenia lasting greater than 2 weeks.

Results: 13 patients enrolled (6 primary refractory and 7 relapsed HL). Median age 32 (range 21–39). 3 patients were treated at dose levels 0 and 1 and 7 patients were treated at dose level 2. 12 patients were evaluable for toxicity and response. The ORR was 75% with 25% CR (1 primary refractory, 2 relapsed) and 50% PR (1 primary refractory, 5 relapsed). PET/CT scans showed negativity in all patients who responded to treatment. 8/9 patients who responded to treatment underwent ASCT (1 patient declined ASCT). All patients who underwent ASCT had successful pheresis and engraftment. At median follow-up of 12 months all 8 patients treated with ASCT are free of relapse. Treatment was well tolerated with no DLTs noted. Reversible grade 4 neutropenia and thrombocytopenia occurred respectively in 33% and 50% of the patients. Median day for retreatment for cycle 2 was D20 and for cycle 3 was D21. There have been no toxicities of peripheral neuropathy, febrile neutropenia, or infection.

Conclusions: Our data suggests favorable tolerability and efficacy of bortezomib plus ICE in patients with relapsed/refractory Hodgkin lymphoma. We are planning to confirm these promising results in a randomized phase II trial.

Disclosures: No relevant conflicts of interest to declare.

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