Brentuximab Vedotin as Another Therapeutic Option in Cutaneous T-Cell Lymphoma
Current systemic treatment for patients with cutaneous T-cell lymphoma (CTCL) unfortunately has limited efficacy, achieving low response rates and short-lasting remissions. Moreover, there is no curative therapy modality for advanced stages of CTCL. However, the results of the recently concluded ALCANZA clinical trial indicate the potential of brentuximab vedotin in this indication.
ALCANZA Study
The phase III ALCANZA study compared the anti-CD30 antibody-drug conjugate brentuximab vedotin against standard care (methotrexate or bexarotene) in CTCL, particularly mycosis fungoides (MF) and primary cutaneous anaplastic large cell lymphoma (pcALCL), which express the CD30 surface antigen. This study achieved a high proportion of clinically significant lasting responses with brentuximab vedotin (BV). This finding has the potential to change the therapy for relapsed/refractory CTCL.
The ALCANZA study introduced a new primary endpoint— the proportion of patients achieving an objective overall response lasting at least 4 months (ORR4), which reflects both the response rate and the duration of response without the influence of subsequent treatments. This parameter can thus be considered a clinically meaningful goal.
Study Findings
During a follow-up of 22.9 months, a significantly better ORR4 was observed in patients treated with brentuximab vedotin compared to the physician's choice therapy (56.3 vs. 12.5%; p < 0.0001). The proportion of patients achieving an objective response of any duration was also higher in the BV group (67 vs. 20%; p < 0.0001), as was the achievement of complete response (16 vs. 2%; p=0.0046). Additionally, a significant advantage of BV was observed in terms of progression-free survival (median 16.7 vs. 3.5 months; hazard ratio [HR] 0.27; p < 0.0001) and time to next treatment (14.2 vs. 6.1 months; HR 0.335; p < 0.001).
In the ALCANZA study, CD30 positivity was defined as the presence of ≥ 10% CD30+ malignant cells or lymphoid infiltrates. No correlation was observed between CD30 expression and the ORR4 parameter, with responses seen across various levels of CD30 expression. For several reasons, it is very important to correctly determine CD30 expression using a sensitive and reliable method and to establish a consensus definition of CD30 positivity.
Another observed fact was a clinically significant reduction in symptoms associated with skin changes.
In terms of the safety profile, no new adverse events were observed, although overall more adverse events were noted with BV administration. Most cases of treatment discontinuation were due to peripheral neuropathy, a well-described adverse effect. It was observed in 67% of treated patients, but only in 14% did it lead to treatment discontinuation.
Conclusion
The results of the ALCANZA study provided further evidence of the role of brentuximab vedotin as a possible and important treatment option for patients with relapsed or resistant CD30-positive primary cutaneous anaplastic large cell lymphoma or mycosis fungoides.
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Source: Prince H. M., Gautam A., Kim Y. H. Brentuximab vedotin: targeting CD30 as standard in CTCL. Oncotarget 2018; 9 (15): 11887–11888, doi: 10.18632/oncotarget.24472.
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