Background. Treatment-related mortality and inferior responses to chemotherapy lead to poorer outcomes for patients aged ≥60 years with newly diagnosed Hodgkin lymphoma (HL). This phase 2, frontline, open-label study is evaluating safety, efficacy, and durability of response to treatment with brentuximab vedotin (BV) as monotherapy and in combination with dacarbazine (DTIC) or bendamustine. The primary endpoint is objective response rate (ORR) (NCT01716806).
Methods. Patients with classical HL who were ineligible for or declined initial conventional chemotherapy and had ECOG ≤3 were eligible. The study evaluated cohorts of 1.8 mg/kg BV (16 cycles), 1.8 mg/kg BV + 375 mg/m2 DTIC (12 cycles), and 1.8 mg/kg BV + 90 or 70 mg/m2 bendamustine (starting dose reduced to improve tolerability after 10 patients treated) (6 cycles). Patients with clinical benefit could subsequently continue BV treatment. Responses were assessed per the Revised Response Criteria for Malignant Lymphoma (Cheson 2007).
Results. Enrollment was completed sequentially (treated patients: n=27 BV; n=22 BV+DTIC; n=20 BV+bendamustine), all patients are off treatment, and 44 remain in long-term follow-up (n=16 BV; n=18 BV+DTIC; n=10 BV+bendamustine). Overall, median age was 76 years (range, 62–92). At baseline, 70% of patients had Stage III-IV HL, 13% presented with bulky disease, 41% had B symptoms, 25% had ECOG 2-3, and 72% were ineligible for frontline chemotherapy. Treatment was discontinued for adverse events (n=35; mostly peripheral neuropathy, n=24), progressive disease (PD; n=15), or other reasons (n=19). Although no specific safety signal was identified, the sponsor suspended treatment with bendamustine because the tolerability did not meet the study goal of defining a low toxicity regimen for this patient population (Table). Median number of treatment cycles, median observation time, ORR, complete remission (CR) rate, median progression-free survival (PFS), and overall survival (OS) are presented by cohort (Table).
Conclusions. Both BV monotherapy and BV+DTIC appear tolerable and yield high response rates (ORR 92-100%) in this fragile patient population. Furthermore, the combination with DTIC appears to increase the durability of response without increasing toxicity; and therefore, may represent a reasonable frontline treatment option for elderly HL patients. Other treatment combinations are being considered.