Frontline brentuximab vedotin in Hodgkin lymphoma and CD30-expressing peripheral T-cell lymphoma for older patients and those with comorbidities.

Abstract

TPS8069 Background: Older patients and those with significant comorbidities have not attained outcomes seen in younger patients with classical Hodgkin lymphoma (cHL) and CD30-expressing peripheral T-cell lymphoma (PTCL). Five-year progression-free survival (PFS) was 30%–45% in older HL patients treated with combination chemotherapy versus 75%–80% in younger patients (Evens 2008; Proctor 2009). Similarly, when adjusted for age, a Charleston Comorbidity Index ≥2 was independently associated with worse overall survival (HR=1.63) and PFS (HR=1.54) (Ellin 2018). Brentuximab vedotin (BV, ADCETRIS), a CD30-directed antibody-drug conjugate, has robust activity in cHL patients refractory to several lines of chemotherapy. BV monotherapy in 27 cHL patients aged ≥60 years had a 92% objective response rate (ORR) and 73% achieved complete remission (Forero-Torres, 2015). BV was also active and well-tolerated in CD30-expressing PTCL patients with relapsed or refractory disease (Horwitz 2014). Frontline BV monotherapy may have the potential to be an active and well-tolerated treatment for cHL and PTCL patients who are older or have significant comorbidities, which are populations with high unmet need. Methods: This phase II, open-label study, SGN35-015 (NCT01716806), has added 2 cohorts to evaluate the efficacy and tolerability of BV monotherapy in treatment naive patients with cHL, (Part E), or CD30-expressing PTCL (Part F, n~50 each) who are unsuitable for conventional combination therapy due to comorbidity-related factors as determined by a Cumulative Illness Rating Scale (CIRS) score ≥10 or dependence on others for any instrumental activities of daily living. Eligible patients must also have an Eastern Cooperative Oncology Group (ECOG) performance status ≤3 and measurable disease ≥1.5 cm per radiographic techniques. BV (1.8 mg/kg) will be administered as a single intravenous infusion on day 1 of each 2-day cycle. Patients achieving a complete remission, partial remission, or stable disease will receive up to 16 cycles of treatment. Response will be assessed by blinded independent central review of spiral CT and PET scans at Cycles 2, 6, 11, and at end of treatment to be graded per Lugano 2014. The primary objective of these cohorts is to assess ORR of frontline therapy with single-agent BV in patients who have significant comorbidities. Clinical trial information: NCT01716806 .