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Brentuximab Vedotin Plus Bendamustine Shows Hodgkin's Lymphoma Salvage Therapy Potential

Anti-CD30 antibody-based therapy could offer alternative to platinum-based chemotherapy for hard to treat Hodgkin's lymphoma
04 Jan 2018
Anticancer Agents;  Lymphomas;  Therapy;  Biological Therapy
By Lynda Williams, Senior medwireNews Reporter

medwireNews: Preliminary trial results indicate that patients with relapsed or refractory Hodgkin’s lymphoma (HL) might benefit from a salvage treatment strategy of the anti-CD30 agent brentuximab vedotin plus bendamustine.

“Our results suggest that brentuximab vedotin plus bendamustine could replace platinum-based chemotherapy regimens before autologous stem cell transplantation [ASCT]”, postulate the investigators in The Lancet Oncology.

“Additionally, the favourable toxicity profile, coupled with the regimen being an outpatient regimen, reduces the toxicity burden for these patients who have a high prospect of cure, hopefully reducing the long-term complications of chemotherapy in this patient population”, write Owen O’Connor, from Columbia University Medical Center in New York, USA, and co-authors.

The phase I–II trial included 64 HL patients with biopsy-confirmed CD30-positive tumours and an ECOG performance status no higher than 2, all of whom had received at least one multi-agent chemotherapy regimen. One patient with anaplastic large-T-cell lymphoma who met these criteria was also included.

In the first phase, a maximum tolerated dose was not reached in the 28 patients given brentuximab vedotin 1.2 mg/kg or 1.8 mg/kg on day 1 of a 21-day cycle, plus bendamustine at a dose of 70, 80 or 90 mg/m2 on days 1 and 2. Dose-limiting toxicities were reported in three patients, namely grade 4 neutropenia in two cases and diffuse rash in one individual.

The overall response rate in phase I was 61%, with a complete response in 18% and a partial response in 43%, the latter of which included the patient with anaplastic large-T-cell lymphoma.

The recommended dose was set at brentuximab vedotin 1.8 mg/kg plus bendamustine 90 mg/m2, the researchers say. Of the 37 patients given this dose in phase II, 78% achieved an overall response, including a complete response in 43% and a partial response in 35%, with 14% experiencing stable disease and 8% progression. These responses lasted a median of 3.95 months; the median overall survival and progression-free survival durations were unreached in this cohort.

Grade 3 lung infection was reported in 14% of phase II patients, while grade 3–4 neutropenia occurred in 25% of phase I and II patients combined. Treatment in phase II was discontinued in two patients because of kidney infection or dehydration.

“The immediate implications of the brentuximab vedotin plus bendamustine regimen is that some patients have a durable progression-free survival benefit, despite having chemotherapy-resistant disease”, comment Owen O’Connor et al.

They conclude: “Coupled with ASCT, this combination therapy might achieve a substantial improvement in these patients compared with traditional, platinum-based salvage regimens. 

“Further studies, preferably randomised trials that will allow formal cross-regimen efficacy comparisons, are warranted.”

Reference

O’Connor OA, Lue JK, Sawas A, et al. Brentuximab vedotin plus bendamustine in relapsed or refractory Hodgkin’s lymphoma: an international, multicentre, single-arm, phase 1–2 trial. Lancet Oncol; Advance online publication 21 December 2017. DOI: http://dx.doi.org/10.1016/S1470-2045(17)30912-9

Last update: 04 Jan 2018

medwireNews is an independent medical news service provided by Springer Healthcare. © 2018 Springer Healthcare part of the Springer Nature group

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