Introduction: Outcomes for older patients (pts) with HL remain sub-optimal. We initiated a multicenter study examining sequential brentuximab vedotin (BV) given before and after AVD chemotherapy (NCT01476410).
Methods: Pts ages ≥60 years with stage II-IV, untreated HL were eligible. All pts received 2 “lead-in” cycles of single-agent BV 1.8 mg/kg (q 3 weeks), followed by 6 cycles of standard AVD chemotherapy. Responding pts then receieved consolidation therapy (Tx) with BV x 4 cycles. Study design is Simon two-stage with plan of 48 total pts. The primary endpoint is complete remission (CR) rate after AVD (ie, prior to BV consolidation) using FDG-PET. If ≥12 CRs were observed among 20 evaluable pts, accrual continued to the 2nd stage.
Results: 26 pts enrolled to the first study stage, of which 20 were evaluable for response. Characteristics for all pts included: median age 69 years (60-88); median ECOG PS of 1 (0-2); 92% stage III/IV disease; IPS 3-7 in 54%; and median CIRS co-morbidity score 5 (0-19). 6 pts were non-evaluable for response (n=3 withdrew consent/refused further therapy; n=2 toxicity; and n=1 death due to pancreatitis). Among 20 evaluable pts, overall response rate (ORR) to BV lead-in was 85% with 30% CR. After 3 AVD cycles, ORR and CR rates were 95% and 70%, respectively. The best ORR (including after BV consolidation therapy) was 95% with a CR rate of 90%. By intent-to-treat, best ORR and CR rates were 81% and 77%, respectively. Grade 3/4 AEs occurring in >1 pt were infection (15%), pancreatitis (4%), and peripheral neuropathy (PN) (4%); 31% of pts experienced grade 2 PN. Reasons for discontinuation of Tx included: 7/26 (27%) completed Tx; 7/26 (27%) on active Tx; 4/26 (15%) due to toxicity (grade 2: infusion reaction, hepatic, pneumonitis; and grade 3 wound infection); 3/26 (12%) refused additional Tx; 3/26 (12%) discontinued for PN (all grade 2 status-post cycles 6, 8,10); 1/26 (4%) due to lack of response; and 1 (4%) death (due to pancreatitis). At median follow-up of 22 months, 92% of all pts are alive, the progression-free survival is 85%, and notably, 95% of all evaluable pts are disease-free.
Conclusions: Sequential integration of BV before and after standard AVD chemotherapy for newly diagnosed older HL pts is feasible and highly promising. The planned interim analysis confirmed the requisite CR rate needed for continuation to the 2nd stage of this multicenter phase II study. Updated results will be reported at the meeting.