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Brentuximab vedotin shows superiority to standard therapy for cutaneous T cell lymphoma

Dr. Joseph Delano Fule Robles
21 Dec 2016

Findings from a phase III trial show that the anti-CD30 antibody-drug conjugate, brentuximab vedotin (BV), is superior to methotrexate or bexarotene in the efficacy endpoint of overall response rate (ORR) lasting ≥4 months in the treatment of cutaneous T cell lymphoma (CTCL).

Results of ALCANZA, the first trial testing a new agent against standard therapy in CTCL, were presented recently at the American Society of Hematology (ASH) 58th Annual Meeting. [ASH 2016, abstract 182]

The authors reported that at a median follow-up of 17.5 months, the primary endpoint of ORR lasting ≥ 4 months was achieved in 56 percent of patients treated with BV vs 13 percent of those treated with standard therapy (methotrexate or bexarotene) (p<0.0001). ORR (67 vs 20 percent) and complete response (CR) rates (16 vs 2 percent) were also significantly higher in the BV vs standard therapy group (p<0.01 for both).

BV also fared better than standard therapy in terms of the secondary endpoints of progression-free survival (PFS) (median,16.7 vs 3.5 months; hazard ratio [HR], 0.270; p<0.0001) and symptom reduction (measured by Skindex-29) (-27.96 vs -8.62; p<0.0001).

“These compelling results have potential practice-changing implications,” said investigator Dr Youn Kim from the Stanford University School of Medicine, Stanford, California, US.

In the study, 128 CTCL patients expressing CD30 who had received ≥1 prior systemic or radiotherapy were randomized receive either BV 1.8 mg/kg intravenously once every 3 weeks, or standard therapy with methotrexate (5–50 mg) orally once weekly or bexarotene (300 mg/m2) orally once daily.

BV, is an antibody-drug conjugate targeting CD30. The anti-CD30 antibody is coupled with a cytotoxic agent, monomethyl auristatin E, via a peptide linker and is released to cause cell death by induced growth arrest and apoptosis when the complex comes in contact with CD30-containing tumour cells. [Blood 2014;124:3197-3200]

Serious adverse effects were seen in 29 percent of patients in each arm. The rate of peripheral neuropathy of any grade was higher in patients receiving BV vs methotrexate or bexarotene (67 vs 6 percent). However, 82 percent of patients who developed peripheral neuropathy had improvement or resolution of symptoms at the last follow-up. Discontinuation of treatment due to adverse effects was more common in the BV vs standard therapy group (24 vs 8 percent).

CTCLs are a heterogeneous group of disease composed of a clonal population of skin-homing malignant T or natural killer (NK) cells. Each entity has unique prognostic and predictive characteristics. CTCLs are generally considered incurable with main goals of therapy being control of symptoms, cosmesis and extending survival. [J Clin Pathol 2015;68:1003-1010]

The multicentre, open-label ALCANZA trial is the first study that demonstrated superior outcomes with a drug compared with standard therapy for CTCL. 

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Most Read Articles
Roshini Claire Anthony, 6 days ago

Treatment failure in osteoporosis remains a problem, even among patients who are treatment-adherent, according to a presentation at the recent meeting of the Asian Federation of Osteoporosis Societies (AFOS 2017), held in Kuala Lumpur, Malaysia. 

Elvira Manzano, 6 days ago
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Yesterday
Drinking coffee, whether caffeinated or decaffeinated, is associated with a reduced risk of cardiovascular disease (CVD) and ischaemic heart disease (IHD) mortality in patients with a prior myocardial infarction (MI), according to a recent study.
2 days ago
Breast cancer patients have notably different microbiomes in the local breast tissue and urinary tract, a recent study reveals. Particularly, species in the Methylobacterium genus are reduced in the local breast tissue while the urinary tract is enriched in gram-positive bacteria.