BRENTUXIMAB VEDOTIN VS PHYSICIAN'S CHOICE IN CTCL PATIENTS FROM THE PHASE 3 ALCANZA STUDY: ANALYSIS OF OUTCOMES BY CD30 EXPRESSION

Introduction: The Phase 3 ALCANZA study showed significant, durable responses with the CD30-directed antibody-drug conjugate brentuximab vedotin (BV) compared with physician's choice (PC) of methotrexate (MTX) or bexarotene (Bex) for CD30-positive (CD30+) cutaneous T cell lymphoma (CTCL). Uniform CD30 expression on neoplastic cells is characteristic of primary cutaneous anaplastic large cell lymphoma (pcALCL), whereas CD30 is variably expressed among other subtypes including mycosis fungoides (MF). We examined the outcomes associated with treatment using BV and MTX / Bex by CD30 expression in patients treated on the ALCANZA study. Methods: Adults with previously treated CD30+ MF or pcALCL were enrolled. MF patients had ≥2 skin biopsies from separate lesions and pcALCL patients had ≥1. Patients were scored CD30+ if ≥1 biopsy had ≥10% CD30+ lymphoid cells at any intensity above background staining noted by the corresponding negative control, as determined using an investigational Ventana immunohistochemical diagnostic test, assessed centrally. We compared the proportion of MF subgroup patients with objective response lasting ≥4 months (ORR4; ALCANZA primary endpoint) and PFS in patients with all biopsies ≥10% CD30+ (CD30min ≥ 10%) vs ≥1 biopsy <10% CD30+ (CD30min < 10%). Patients were randomized 1:1 to BV 1.8 mg/kg IV, Q3W, or PC for up to 16 three-week cycles. Results: Overall, 125/184 (68%) MF and 44/47 (94%) pcALCL patients were scored as CD30+ at screening evaluation. High inter-lesional variability in CD30 expression was seen in MF patients; 55/125 CD30+ MF patients (44%) had ≥1 biopsy with low (<10%) or undetectable CD30. In total, 100/125 CD30+ MF patients (80%) were eligible and enrolled; 50 per treatment arm. In the BV arm, ORR4 was higher in MF patients with CD30min ≥ 10% vs <10% (57.1% vs 40.9%); median PFS with BV was higher in the CD30min < 10% group (27.9 months) than in the CD30min ≥ 10% group (17.2 months) (Table). ORR4 with BV was greater than PC over all CD30 expression ranges (CD30min < 5%, 38% vs 13%; CD30 ≥ 5–≤20%, 35% vs 10%; CD30 > 20%, 76% vs 7%, respectively). Conclusions: Notable inter-patient or inter-lesional variability in CD30 expression was seen in MF patients. BV produced highly superior ORR4 and PFS endpoints compared with PC regardless of CD30min expression level. Hazard ratio [95% CI] Keywords: brentuximab vedotin; CD30; cutaneous T-cell lymphoma (CTCL).