Brentuximab vedotin produces durable responses and prolongs progression-free survival (PFS), when compared with physician’s choice of therapy, in previously treated patients with CD30-expressing cutaneous T-cell lymphoma (CTCL), according to final results from the ALCANZA study published in Blood Advances.
The phase 3 ALCANZA trial (ClinicalTrials.gov Identifier: NCT01578499) enrolled 131 patients with mycosis fungoides (MF) or primary cutaneous anaplastic large-cell lymphoma (C-ALCL) who had received at least 1 prior systemic therapy or radiotherapy.
The intent-to-treat population included 128 patients, 97 with MF and 31 with C-ALCL, who were randomly assigned to receive brentuximab vedotin (66 patients) or physician’s choice of oral methotrexate or bexarotene (62 patients).
At a median follow-up of 45.9 months, the final analysis showed improved responses with brentuximab vedotin over physician’s choice, per independent review.
The overall response rate was 65.6% with brentuximab vedotin and 20.3% with physician’s choice (P <.001). The proportion of patients achieving an objective response lasting at least 4 months was 54.7% and 12.5%, respectively (P <.001). The complete response rate was 17.2% and 1.6%, respectively (P =.002).
At a median follow-up for PFS of 36.8 months, the PFS was significantly longer in the brentuximab vedotin arm than in the physician’s choice arm — 16.7 months and 3.5 months, respectively (hazard ratio [HR], 0.38; 95% CI, 0.25-0.58; P <.001).
At a median follow-up of 45.9 months, there was no significant difference in overall survival (OS) between the treatment arms. The estimated 3-year OS rates were 64.4% in the brentuximab vedotin arm and 61.9% in the physician’s choice arm (HR, 0.75; 95% CI, 0.42-1.32 P =.310).
However, a subanalysis of patients with advanced-stage MF showed an improvement in OS with brentuximab vedotin over physician’s choice (P =.021).
At a median follow-up of 37.3 months, the time to next treatment was significantly longer with brentuximab vedotin than with physician’s choice — 14.2 months and 5.6 months, respectively (HR, 0.27; 95% CI, 0.17-0.42; P <.001).
At 1 year, the probability of patients not requiring subsequent antineoplastic treatment was 65.5% in the brentuximab vedotin arm and 13.4% in the physician’s choice arm.
Grade 1-2 peripheral neuropathy (PN) was seen in 67% of patients in the brentuximab vedotin arm (44/66) and 6% of those in the physician’s choice arm (4/62). Six patients in the brentuximab vedotin arm had grade 3 PN, and there were no cases of grade 4 PN.
By the final data cutoff, 86% of PN cases in the brentuximab vedotin arm had resolved completely or had improved by at least 1 grade. There were 18 patients in the brentuximab vedotin arm who had ongoing grade 1-2 PN, but there were no ongoing grade 3-4 PN events.
“This final analysis from ALCANZA shows that, with longer follow-up and increased treatment exposure, brentuximab vedotin provides a durable, robust clinical benefit in previously treated patients with CD30-expressing MF and C-ALCL through improved global response rates … and prolonged PFS … compared with physician’s choice,” the study authors concluded.
Disclosures: This research was supported by Seagen Inc., and Millennium Pharmaceuticals, Inc. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Horwitz SM, Scarisbrick JJ, Dummer R, et al. Randomized phase 3 ALCANZA study of brentuximab vedotin vs physician’s choice in cutaneous T-cell lymphoma: Final data. Blood Adv. Published online September 10, 2021. doi:10.1182/bloodadvances.2021004710