Brentuximab vedotin and ESHAP is highly effective as second-line therapy for Hodgkin lymphoma patients (long-term results of a trial by the Spanish GELTAMO Group)

Abstract

Background: In this work, we assessed the efficacy and safety of brentuximab vedotin (BV) plus ESHAP (BRESHAP) as secondline therapy for Relapsed/Refractory Hodgkin lymphoma (RRHL) to improve the results before autologous stem-cell transplantation (ASCT).Patients and methods: This was a multicenter, open-label, phase I-II trial of patients with RRHL after first-line chemotherapy. Treatment had three 21-day cycles of etoposide, solumedrol, high-dose AraC, and cisplatin. BV was administered at three dose levels (0.9, 1.2, and 1.8 mg/kg) intravenous on day -1 to 3 þ 3 cohorts of patients. Final BV dose was 1.8 mg/kg. Responding patients proceeded to ASCT, followed by three BV courses (1.8 mg/kg, every 21 days). Main end points for evaluation were maximum tolerable dose and overall and complete response (CR) before ASCT.Results: A total of 66 patients were recruited (median age 36 years; range 18-66): 40 were primary refractory, 16 early relapse and 10 late relapse. There were 39 severe adverse events were reported in 22 patients, most frequently fever (n ¼ 25, 35% neutropenic), including 3 deaths. Grade 3-4 hematological toxicity presented in 28 cases: neutropenia (n ¼ 21), thrombocytopenia (n ¼ 14), and anemia (n ¼ 7). Grade !3-4 extrahematological adverse events (!5%) were non-neutropenic fever (n ¼ 13) and hypomagnesaemia (n ¼ 3). Sixty-four patients underwent stem-cell mobilization; all collected >2Â10e6/kg CD34þ cells (median 5.75; range 2.12-33.4). Overall response before transplant was 91% (CI 84% to 98%), including 70% (CRs 95% CI 59% to 81%). 60 patients were transplanted with no failure engraftments. Post-transplant response was CR in 49 patients (82% CI 73% to 91%) and partial responses in six (10% CI 5% to 15%). After a mean follow-up of 27 months, the 30-month time to treatment to failure was 74% (95% CI 68% to 80%), progression-free survival 71% (95% CI 65% to 77%), and overall survival 91% (CI 84% to 98%). Conclusion:BRESHAP looks a safe and effective pre-transplant induction regimen, does not jeopardize transplant and allows long-term remissions and survival.

Brentuximab vedotin in association with bendamustine in refractory or multiple relapsed Hodgkin lymphoma. A retrospective real‐world study

“…These very encouraging results with BvB as well those reported with the association of Bv with other classic chemotherapeutics agents 44,45 and those with checkpoint inhibitors 46…”

“…These very encouraging results with BvB as well those reported with the association of Bv with other classic chemotherapeutics agents and those with checkpoint inhibitors have opened new horizons in the treatment of patients with RR‐cHL . Due to the availability of diverse novel effective second‐line combinations for RR‐cHL, scientific efforts are required to identify the best algorithm for their timely use along with the natural history of the disease taking account of their efficacy and toxicity.…”

Treatment with brentuximab vedotin plus bendamustine in unselected patients with CD30‐positive aggressive lymphomas

“…Recently, a phase 1/2 trial by Garcia‐Sanz et al investigated the addition of brentuximab vedotin (BV) to ESHAP in patients with relapsed or refractory cHL as induction therapy before planned ASCT. The combination showed improved efficacy when indirectly compared to ESHAP alone while still being tolerable . BV in combination with other chemotherapy agents (doxorubicin, vinblastine, and dacarbazine) also has already been shown to be superior to standard chemotherapy with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in the frontline treatment of advanced HL in the ECHELON‐1 trial .…”

“…The combination showed improved efficacy when indirectly compared to ESHAP alone while still being tolerable. 6 BV in combination with other chemotherapy agents (doxorubicin, vinblastine, and dacarbazine) also has already been shown to be superior to standard chemotherapy with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in the frontline treatment of advanced HL in the ECHELON-1 trial. 7 Two-phase 1/2 studies by LaCasce et al 8 and O'Connor et al 9 in 2018 showed that therapy with BV could achieve high CR rates as salvage therapy and was still effective in heavily pretreated patients, while having manageable side effects when indirectly compared to platinum-based therapies.…”

Treatment of Hodgkin Lymphoma – New and Developing Therapies and Their Potential Role in Standard of Care

“…as single-agent or in combination with chemotherapy either sequentially or concurrently (with augmented ICE/ICE, DHAP, ESHAP), reported ORRs of 68-75% and CRs of 35-50% for single agent therapy,[60][61][62] as well as ORRs ranging from 87-100% and CRs ranging from 70-100% with combination therapy 59,[63][64][65][66][67]. In addition, several recent studies have evaluated the use of brentuximab vedotin as first-salvage therapy for relapsed or refractory Hodgkin lymphoma in combination with bendamustine (as a potentially less toxic alternative to platinum-or gemcitabine-based chemotherapy),…”