Brentuximab Vedotin for the Treatment of Patients with Hodgkin Lymphoma

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Key points

  • Brentuximab vedotin, an antibody-drug conjugate that targets CD30, is one of the most active single agents for the treatment of patients with relapsed classic Hodgkin lymphoma.

  • Brentuximab vedotin should not be combined with bleomycin, as the combination can cause excessive pulmonary toxicity. When combined with front-line ABVD, bleomycin is eliminated from the regimen.

  • The most common brentuximab vedotin toxicity is cumulative but reversible neuropathy.

  • Brentuximab vedotin can be safely

Phase I studies

The initial multicenter first-in-man phase I study enrolled 45 patients with relapsed or refractory CD30-positive hematologic cancers, of whom 93% had HL.13 Although there was no limit to the number of prior regimens, patients were treated with a median of 3 prior regimens, and 73% of the patients had undergone prior autologous stem cell transplantation (ASCT). Patients were treated with escalating doses of brentuximab vedotin (from 0.1 mg/kg to 3.6 mg/kg) in a standard 3 + 3 phase I design.

Pivotal phase II study

Based on the encouraging results that were observed in the phase I studies, a pivotal phase II clinical trial in patients with relapsed HL after receiving ASCT was conducted.15 Patients received brentuximab vedotin 1.8 mg/kg (capped dose at 180 mg) every 3 weeks by a short 30-minute outpatient intravenous infusion for up to 16 cycles. For those who had a response and an acceptable toxicity profile, up to 16 doses or 1 year of therapy was allowed. Of the 102 patients enrolled, 53% were female

Brentuximab vedotin in relapsed pretransplant and transplant-ineligible patients with Hodgkin lymphoma

The Food and Drug Administration (FDA)-approved indication for brentuximab vedotin is for the treatment of patients with HL after failure of ASCT or after failure of at least 2 prior multiagent chemotherapy regimens in patients who are not ASCT candidates. Emerging data suggest that introducing brentuximab vedotin in second-line regimens may also be beneficial. Results from an ongoing study using a weekly schedule of brentuximab vedotin at 1.2 mg/kg for 3 weeks in 4 weekly cycles demonstrated

Experience with brentuximab vedotin in patients undergoing allogeneic stem cell transplantation

Before the FDA approval of brentuximab vedotin, allogeneic stem cell transplantation was routinely offered to young, healthy patients after failing ASCT. At present, brentuximab vedotin is frequently used as a bridge to an allogeneic stem cell transplant. While this approach may provide high response rates with little toxicity, it remains unclear whether all patients who achieve complete remission after brentuximab vedotin will require consolidation with allogeneic stem cell transplantation.18

Brentuximab vedotin in front-line regimens

To improve the cure rate achieved with front-line chemotherapy regimens, brentuximab vedotin was recently combined with the standard ABVD (Adriamycin/Bleomycin/Vinblastine/Dacarbazine) regimen in a phase I study.19 Initially, escalating doses of brentuximab vedotin (0.6, 0.9, 1.2 mg/kg) were combined with ABVD, given every 2 weeks. Although the clinical efficacy of brentuximab vedotin plus ABVD in the first 25 patients was excellent, up to 40% of the patients developed pulmonary toxicity.

Summary

After more than 3 decades since the discovery of the CD30 molecule on the HRS cells of the in vitro cell line L428, therapeutic targeting of CD30 has become a reality.20 In fact, brentuximab vedotin is one of the most effective single agents in patients with relapsed HL (Fig. 1). Randomized clinical trials incorporating brentuximab vedotin in front-line, pretransplant, and posttransplant regimens are under way. Additional studies are addressing the potential value of brentuximab vedotin in

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