Brentuximab Vedotin ‘Potentially Practice Changing’ For Cutaneous T-Cell Lymphoma

Patients with relapsed or refractory CD30-positive cutaneous T-cell lymphoma have higher rates of response to brentuximab vedotin than to methotrexate or bexarotene

medwireNews: Brentuximab vedotin has achieved a significant improvement in the proportion of patients with relapsed or refractory CD30-positive cutaneous T-cell lymphoma who achieve an enduring objective global response lasting at least 4 months (ORR4) compared with physician’s choice of chemotherapy, ALCANZA results show.

After a median of 22.9 months, 56.3% of 64 patients randomly assigned to receive brentuximab vedotin 1.8 mg/kg every 3 weeks met the ORR4 criteria compared with 12.5% of 64 patients given methotrexate 5–50 mg/week or bexarotene 300 mg/m2 per day.

“We consider these results to be potentially practice changing and as a consequence approval is being sought from the US Food and Drug Administration and European Medicines Agency for the use of brentuximab vedotin in the treatment of patients with cutaneous T-cell lymphoma who require systemic therapy”, the authors write in The Lancet.

The study participants, recruited from 13 countries, all had CD30-positive mycosis fungoides or primary cutaneous anaplastic large-cell lymphoma (pcALCL), and had previously received at least one systemic course of therapy or radiotherapy.

The improvement in ORR4 was consistent across all key patient groups, including patients with skin-only disease or extracutaneous disease, report lead author H Miles Prince, from the Peter MacCallum Cancer Centre in Melbourne, Victoria, Australia, and team.

Brentuximab vedotin-treated patients also had a significantly higher rate of objective response of any duration than those given physician’s choice of chemotherapy (67 vs 20%) and a significantly higher rate of complete response (16 vs 2%).

Furthermore, 77% of 48 brentuximab vedotin-treated patients with mycosis fungoides had a 50% or greater reduction in their modified severity weighted assessment tool score compared with 41% of 49 controls. And 63% of 16 patients with pcALCL in the brentuximab vedotin arm experienced 100% clearance of skin disease.

Median progression-free survival was 16.7 months with brentuximab vedotin versus 3.5 months with chemotherapy, giving a significant hazard ratio of 0.27.

“These data provide compelling evidence favouring brentuximab vedotin over methotrexate or bexarotene for the treatment of relapsed or refractory CD30-positive cutaneous T-cell lymphoma”, the researchers say.

Safety analysis showed that the median brentuximab vedotin treatment duration was 269 days compared with 77 days of methotrexate and 114 days of bexarotene.

Serious adverse events occurred in 29% of both the brentuximab vedotin and combined chemotherapy arms, with discontinuation due to adverse events reported in 24% versus 8%. One patient given brentuximab vedotin died from tumour lysis at sites of visceral lymphoma associated with the study agent.

The authors of a comment accompanying the study say that the “ALCANZA study represents a major milestone in the development of effective systemic therapies for cutaneous T-cell lymphoma”, and suggest that “the greater impact of brentuximab vedotin may be seen in patients with advanced-stage mycosis fungoides.”

Pierluigi Porcu and Joya Sahu, from the Thomas Jefferson University in Philadelphia, Pennsylvania, USA, now recommend further research into brentuximab vedotin at an earlier stage of treatment, as well as in combination with other agents, such as immune checkpoint inhibitors, lenalidomide, histone deacetylase inhibitors or total skin electron beam radiation.

Reference

Prince HM, Kim YH, Horwitz SM, et al. Brentuximab vedotin or physician’s choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial. Lancet; Advance online publication 6 June 2017. DOI: http://dx.doi.org/10.1016/S0140-6736(17)31266-7

Porcu P, Sahu J. A positive randomised trial in cutaneous T-cell lymphoma. Lancet; Advance online publication 6 June 2017. DOI: http://dx.doi.org/10.1016/S0140-6736(17)31473-3

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