In August 2011, the FDA approved brentuximab vedotin, the first agent in this class to be approved for the treatment of HL and systemic anaplastic large-cell lymphoma 79 .

The approval was based on an impressive 87% response rate in cHL patients who had failed both autologous stem cell transplant as well as brentuximab vedotin [1].

Given the findings of relapsed/refractory CD30+ transformed MF she was started on brentuximab vedotin (1.8 mg/kg intravenously every 3 weeks).

Ma H & Abdul-Hay M. Int J Clin Oncol 2017; 22: 18–51. doi:10.1007/s10147-016-1045-2

Figure 3 shows the prognostic value of overexpression of Myc, Bcl-2, Bcl-6, and p53 in diffuse large B-cell lymphoma based on a well-organized large cohort of patients. 10, 11, 12, 13 CD30 CD30, a member of the tumor necrosis factor receptor superfamily, is a transmembrane cell-surface marker expressed by activated B or T cells in normal tissues and is highly expressed by tumor cells in classical Hodgkin lymphoma and anaplastic large cell lymphoma, and a subset of diffuse large B-cell lymphoma and Epstein-Barr virus-driven lymphoproliferative disorders. 126 Immunohistochemical assessment for CD30 is used commonly as a valuable biomarker for classical Hodgkin lymphoma and anaplastic large cell lymphoma diagnosis; soluble CD30 in serum and/or body fluids can independently predict disease progression and poor outcomes of patients with CD30 +  lymphoma. 126  As a result of the physiological highly restricted distribution of CD30 expression and dysregulated signaling pathway in lymphoma subtypes, brentuximab vedotin, an antibody drug conjugate composed of anti-CD30 linked to monomethyl auristain E, has been shown to be an effective therapeutic drug for patients with CD30 + lymphomas, especially for patients with relapsed/ refractory Hodgkin lymphoma, systemic anaplastic large cell lymphoma, as well as a subset of patients with refractory/resistant CD30 +  diffuse large B-cell lymphoma. 126 Bcl-6, Bcl-2, and Myc Bcl-6 has a critical regulatory role in the programming of germinal center B cells and is considered a unique marker for B cells at the germinal center stage of differentiation.

Nivolumab given at 1 mg/kg or 3 mg/kg in weeks 1 and 4, and then every 2 weeks thereafter until disease progression showed an ORR of 87% in 23 patients: six (26%) had a CR, 14 (61%) had a PR. 145, 148 Additionally, three (13%) patients had SD. 148 The progression-free survival rate at 24 weeks was 86%. 148 The patients included in this study were heavily pretreated with 87% having received three or more prior treatments, 78% had received brentuximab vedotin, and 78% had undergone autologous HSCT. 148 Nivolumab was active in all patients regardless of their prior treatment status. 148, 149 In a separate phase I study, pembrolizumab was also evaluated for efficacy and safety in patients with relapsed/refractory HL. 150 All patients had prior exposure to brentuximab vedotin, and 69% of the patients had received autologous HSCT. 150 Among 29 evaluable patients, the ORR was 63%, including six patients with CR, and 13 patients with PR. 150 Six patients obtained SD. 150 With a median observation period of 153 days, the median DoR had not been reached (range 1–185 days). 150 Both of these studies have evaluated the expression of PD-L1 and/or PD-L2 in the tumour cells in patients with available samples, and showed PD-L1 and/or PD-L2 expression by the malignant Reed–Sternberg cells in all cases. 148, 150 Other immune-checkpoint-targeting antibodies in development include anti-PD-L1 and anti-4-1BB antibodies.