- •
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
Brentuximab Vedotin for the Treatment of Patients with Hodgkin Lymphoma
Section snippets
Key points
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
References (21)
- et al.
Molecular cloning and expression of a new member of the nerve growth factor receptor family that is characteristic for Hodgkin's disease
Cell
(1992) - et al.
A phase 1 multidose study of SGN-30 immunotherapy in patients with refractory or recurrent CD30+ hematologic malignancies
Blood
(2008) - et al.
Gemcitabine, vinorelbine, and pegylated liposomal doxorubicin (GVD), a salvage regimen in relapsed Hodgkin's lymphoma: CALGB 59804
Ann Oncol
(2007) CD30-targeted antibody therapy
Curr Opin Oncol
(2011)- et al.
Emerging applications of the tumor necrosis factor family of ligands and receptors in cancer therapy
J Clin Oncol
(2003) - et al.
High serum level of the soluble form of CD30 molecule in the early phase of HIV-1 infection as an independent predictor of progression to AIDS
AIDS
(1994) - et al.
Serum levels of soluble CD30 in chronic hepatitis B virus infection
Clin Exp Immunol
(1996) - et al.
Circulating levels of soluble CD30 are increased in patients with systemic sclerosis (SSc) and correlate with serological and clinical features of the disease
Clin Exp Immunol
(1997) - et al.
Phase I/II study of an anti-CD30 monoclonal antibody (MDX-060) in Hodgkin's lymphoma and anaplastic large-cell lymphoma
J Clin Oncol
(2007) Beyond chemotherapy: new agents for targeted treatment of lymphoma
Nat Rev Clin Oncol
(2011)
Cited by (15)
Investigational Antibody–Drug Conjugates for Treatment of B-lineage Malignancies
2018, Clinical Lymphoma, Myeloma and LeukemiaCitation Excerpt :Approval for frontline use in combination with chemotherapy was based on the randomized phase III ECHELON-1 study, which found significantly improved modified PFS for the combination of BV with AVD (doxorubicin, vinblastine, dacarbazine) compared with standard bleomycin combined with AVD (hazard ratio for progression, death, or modified progression, 0.77; P = .03).76 BV has been widely investigated in B-lineage malignancies and has been extensively reviewed.15,77 We have focused on its combination with checkpoint inhibitors in B-lineage malignancies and its investigational uses in DLBCL.
Molecular heterogeneity in diffuse large B-cell lymphoma and its implications in clinical diagnosis and treatment
2018, Biochimica et Biophysica Acta - Reviews on CancerCitation Excerpt :Combinations of R-CHOP with a variety of single use drugs have been or could be used in clinical trials to add specific targeting to the regimen (Table 3). For example, R-CHOP plus brentuximab vedotin, a CD30 inhibiting antibody approved for Hodgkin's lymphoma [98], produced complete response (CR) in 92% of CD30+ versus 69% of CD- intermediate-high to high risk DLBCL patients [99]. About 41% of DLBCL cases show mutations in the acetyl transferase CREBBP, resulting in activation of BCL6 and inactivation of p53 [100].
Hodgkin lymphoma in children and adolescents: Advances in pathology, diagnosis, and treatment strategies
2020, Indian Journal of Medical and Paediatric OncologyDiffuse large B‑cell lymphoma
2019, Memo - Magazine of European Medical Oncology