Search

The number of patients with primary cutaneous lymphoma (PCL) relative to other non-Hodgkin lymphomas (NHLs) is small and the number of subtypes large. Although clinical trial guidelines have been published for mycosis fungoides/Sézary syndrome, the most common type of PCL, none exist for the other PCLs. In addition, staging of the PCLs has been evolving based on new data on potential prognostic factors, diagnosis, and assessment methods of both skin and extracutaneous disease and a desire to align the latter with the Lugano guidelines for all NHLs. The International Society for Cutaneous Lymphomas (ISCL), the United States Cutaneous LymphomaConsortium (USCLC), and the Cutaneous Lymphoma Task Force of the European Organization for the Research and Treatment of Cancer (EORTC) now propose updated staging and guidelines for the study design, assessment, endpoints, and response criteria in clinical trials for all the PCLs in alignment with that of the Lugano guidelines. These recommendations provide standardized methodology that should facilitate planning and regulatory approval of new treatments for these lymphomas worldwide, encourage cooperative investigator-initiated trials, and help to assess the comparative efficacy of therapeutic agents tested across sites and studies. © 2022 American Society of Hematology

INTRODUCTION: Mycosis fungoides (MF), the most common type of cutaneous T-cell lymphoma, can lead to disfiguring lesions, debilitating pruritus and frequent skin infections. This study assessed response to brentuximab vedotin in patients with MF in the phase III ALCANZA study. METHODS: Baseline CD30 levels and large-cell transformation (LCT) status were centrally reviewed in patients with previously-treated CD30-positive MF using ≥2 skin biopsies obtained at screening; eligible patients required ≥1 biopsy with ≥10% CD30 expression. Patients were categorised as CD30min < 10% (≥1 biopsy with <10% CD30 expression), or CD30min ≥ 10% (all biopsies with ≥10% CD30 expression) and baseline LCT present or absent. Efficacy analyses were the proportion of patients with objective response lasting ≥4 months (ORR4) and progression-free survival (PFS). RESULTS: Clinical activity with brentuximab vedotin was observed across all CD30 expression levels in patients with ≥1 biopsy showing ≥10% CD30 expression. Superior ORR4 was observed with brentuximab vedotin versus physician's choice in patients: with CD30min < 10% (40.9% versus 9.5%), with CD30min ≥ 10% (57.1% versus 10.3%), with LCT (64.7% versus 17.6%) and without LCT (38.7% versus 6.5%). Brentuximab vedotin improved median PFS versus physician's choice in patients: with CD30min < 10% (16.7 versus 2.3 months), with CD30min ≥ 10% (15.5 versus 3.9 months), with LCT (15.5 versus 2.8 months) and without LCT (16.1 versus 3.5 months). Safety profiles were generally comparable across subgroups. CONCLUSION: These exploratory analyses demonstrated that brentuximab vedotin improved rates of ORR4 and PFS versus physician's choice in patients with CD30-positive MF and ≥1 biopsy showing ≥10% CD30 expression, regardless of LCT status. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, NCT01578499.

The primary analysis of the phase 3 ALCANZA trial showed significantly improved objective responses lasting ≥4 months (ORR4; primary endpoint) and progression-free survival (PFS) with brentuximab vedotin vs physician's choice (methotrexate or bexarotene) in CD30-expressing mycosis fungoides (MF) or primary cutaneous anaplastic large-cell lymphoma (C-ALCL). Cutaneous T-cell lymphomas often cause pruritus and pain; brentuximab vedotin improved skin symptom burden with no negative effects on quality of life. We report final data from ALCANZA (median follow-up, 45.9 months). Adults with previously treated CD30-expressing MF/C-ALCL were randomly assigned to brentuximab vedotin (n = 64) or physician's choice (n = 64). Final data demonstrated improved responses per independent review facility with brentuximab vedotin vs physician's choice: ORR4; 54.7% vs 12.5% (P < .001); complete response, 17.2% vs 1.6% (P = .002). Median PFS with brentuximab vedotin vs physician's choice was 16.7 months vs 3.5 months (P < .001). Median time to the next treatment was significantly longer with brentuximab vedotin than with physician's choice (14.2 vs 5.6 months; hazard ratio, 0.27; 95% confidence interval, 0.17-0.42; P < .001). Of 44 patients in the brentuximab vedotin arm who experienced any-grade peripheral neuropathy, (grade 3, n = 6; grade 4, n = 0), 86% (38 of 44) had complete resolution (26 of 44) or improvement to grades 1 and 2 (12 of 44). Peripheral neuropathy was ongoing in 18 patients (all grades 1-2). These final analyses confirm improved, clinically meaningful, durable responses and longer PFS with brentuximab vedotin vs physician's choice in CD30-expressing MF or C-ALCL. This trial was registered at https://www.clinicaltrials.gov as #NCT01578499.