Background:
Brentuximab vedotin (BV), an antibody drug conjugate, selectively induces apoptosis of CD30+ cells. We previously conducted a phase II trial using 1.8 mg/kg dose showing an ORR of 68% and CR of 36% in Hodgkin Lymphoma (HL) patients as first line salvage therapy. We observed that all patients who achieved CR did so after 2 cycles of therapy. However, 3 patients who achieved PR after 2 cycles progressed after 4 cycles of BV. We hypothesize that dose escalation from 1.8 mg/kg to 2.4 mg/kg after cycle 2 CT/PET may convert patients in PR/SD to CR or prevent disease progression.
Patients and Methods:
This is an additional feasibility cohort added to a prospective phase II trial in patients with relapsed/refractory HL. All patients had biopsy proven relapsed/refractory HL post induction therapy. Patients were treated with 1.8 mg/kg of BV intravenously every 3 weeks for 2 cycles followed by CT/PET. Patients in CR after 2 cycles received 2 additional cycles at 1.8 mg/kg. Patients in PR/SD after 2 cycles received dose escalation of 2.4 mg/kg of BV for 2 cycles. The primary endpoint was the CR rate according to Revised Cheson Criteria. Secondary endpoints were toxicities assessment according to NCI CTCAE v 4.0.
Results:
20 patients were accrued and evaluable for response. See table for baseline characteristics. The ORR with 1.8 mg/kg dose at cycle 2 was 85%, CR was 55%, PR was 30%, SD was 10%, and PD was 5%. 8/20 patients were in PR/SD after cycle 2 and received 2.4 mg/kg x 2 doses. 1/6 patients in PR converted to CR and the rest stayed in PR. 2/2 patients in SD stayed in SD. At the end of study, ORR was 85%, CR was 60%, and PD was 5%.
Treatment was well tolerated at both the 1.8 mg/kg and 2.4 mg/kg cohort. There were no significant differences in toxicities between the two cohorts and there were also no grade 4/5 toxicities. The only grade 3 possibly-related toxicity was maculopapular rash that occurred in 2 patients (at 1.8 mg/kg). In the 2.4 mg/kg cohort, grade 2 possibly-related toxicities >20% included fatigue (n=3), back pain (n=2), pruritis (n=2), and rash (n=2). There were no transfusions required and no neutropenic fevers.
Conclusion:
Dose escalation from 1.8 mg/kg to 2.4 mg/kg was able to convert 1/8 (12.5%) patients into CR. No patients developed progressive disease while receiving 2.4 mg/kg. The dosage of 2.4 mg/kg was well tolerated. Dose escalation of BV based on PET 2 is feasible and merits further investigation.