Results of a Multicenter Phase II Trial of Brentuximab Vedotin as Second-Line Therapy before Autologous Transplantation in Relapsed/Refractory Hodgkin Lymphoma

Abstract

This multicenter prospective phase II study examines the activity and tolerability of brentuximab vedotin as second-line therapy in patients with Hodgkin lymphoma that was relapsed or refractory after induction therapy. Brentuximab vedotin (1.8 mg/kg) was administered intravenously on day 1 of a 21-day cycle for a total of 4 cycles. Patients then proceeded to autologous hematopoietic cell transplantation (AHCT), if eligible, with or without additional salvage therapy, based on remission status post brentuximab vedotin. The primary endpoint was overall response rate (ORR). Secondary endpoints were safety, stem cell mobilization/collection, AHCT outcomes and association of CD68+ with outcomes. Of 37 patients, the ORR was 68% (13 complete remission, 12 partial remission). The regimen was well tolerated with few grade 3/4 adverse events including lymphopenia (1), neutropenia (3), rash (2), and hyperuricemia (1). Thirty-three (89%) patients were able to proceed to AHCT, with 24 (65%) in CR at time of AHCT. Thirteen patients in CR, 4 in PR and 1 in SD (49%) received AHCT without salvage combination chemotherapy. CD 68 expression did not correlate with response to brentuximab vedotin. The median number of stem cells mobilized was 6.0 × 106 (2.6–34) and median number of days to obtain minimum collection (2 × 106) was 2 (1–6). Brentuximab vedotin as second-line therapy is active, well tolerated, and allows adequate stem cell collection and engraftment. For Hodgkin lymphoma patients with relapsed/refractory disease post-induction therapy, second-line brentuximab vedotin, followed by combination chemotherapy for residual disease, can effectively bridge patients to AHCT.

Treatment of relapsed and refractory Hodgkin Lymphoma

“…Two studies, both peer reviewed and published, confirm a single agent response rate of > 80% as first salvage treatment, however the complete response rate is <40% (24, 25). Sequential treatment with platinum-based salvage treatment to patients lacking a PET negative response increases the CR rate to >80%.…”

“…Recently, four studies have incorporated BV either sequentially or in combination with chemotherapy as part of a salvage strategy prior to ASCT (24–27). BV comprises an anti-CD30 antibody conjugated by a protease-cleavable linker to a microtubule-disrupting agent, monomethyl auristatin E (MMAE).…”

The role of transplantation in Hodgkin lymphoma

“…Given the efficacy of both BV and anti-PD1 agents in HL, their combination in a chemotherapy-free schedule for firstsalvage treatment is sound, as these agents exploit complementary mechanisms of action on Reed-Sternberg cells. Moreover, anti-PD1 agents may enhance the response rates of pre-ASCT single-agent BV, as documented in earlier trials (Chen et al, 2015a;Moskowitz et al, 2015a). Herrera et al (2018) conducted a phase 1/2 trial of BV in combination with nivolumab (Nivo-BV) in patients with relapsed and refractory HL failing induction therapy.…”

“…Importantly, EFS for patients who were PET‐negative after BV was 92% at 2 years, overlapping with the EFS of those who also received augICE (91%). A second study was a joint collaboration between City of Hope and Weill Cornell (Chen et al , 2015a), and involved 37 patients (65% were primary refractory to first‐line therapy). All of the patients received BV at the dose of 1·8 mg/kg for up to 4 cycles; patients in CR or PR were allowed to mobilise PBSC and to proceed to ASCT, although PR patients could also receive an additional combination chemotherapy before ASCT.…”

A Review of Autologous Stem Cell Transplantation in Lymphoma

“…At 2 years, EFS was better after ASCT for patients who achieved PET negativity compared to patients who remained PET positive prior to ASCT [61]. In study by Chen et al (2015), BV was used as second line agent prior to ASCT (n 37, R/R HL) and showed ORR of 68% (13 CR, 12 PR), and 32 patients (86%) proceeded to ASCT [62]. In AETHERA trial (2015), a cohort of 329 patients with R/R HL was randomized to receive HDT/ASCT followed by maintenance BV treatment (n 165) or to placebo group (n 164).…”