Background: Standard treatment for classical Hodgkin lymphoma (HL) is poorly tolerated by older patients (pts) with comorbidities or frailty and results are disappointing.
Methods: In the international prospective phase II BVB trial (NCT02191930), we evaluated safety and efficacy of brentuximab vedotin (BV, 1.8 mg/kg every 3 weeks) in previously untreated HL patients aged ≥60 years considered unsuitable for combination chemotherapy. The primary endpoint was objective response rate (ORR) assessed by computed tomography after ≥2 cycles of BV. Secondary endpoints included toxicity, progression-free (PFS) and overall survival (OS). For comparison, we evaluated elderly HL patients from a Norwegian population-based cohort diagnosed 2000-2015.
Results: Between 2015 and 2018, we enrolled 20 pts. Nineteen pts with a median age of 82 years (range 62-88) and a median Cumulative Illness Rating Scale for Geriatrics (CIRSG) score of 8 (range 4-14) were evaluable for toxicity, whereas 18 were evaluable for response. With a median of 6 BV cycles given (range 2-16), grade (G) 3 hematological toxicity occurred in 3 pts, with no G4 reported. G3 or 4 infections were seen in 3 and 1 pts, respectively, while non-hematological G3 or 4 toxicities were noted in 7 and 3 pts, respectively. Four (22%) pts had complete and 7 (39%) had partial response (ORR 61%, 95%CI 31-100). One patient received radiotherapy (RT) in remission. With a median follow-up of 30 months, median PFS was 19 months (95%CI 5-30), and median OS was not reached (Figure A+C). Three-year PFS and OS were 27% (95%CI 6-48) and 56% (95%CI 31-81), respectively. In the retrospective cohort, 49 pts had a median age of 81 years (range 65-92) and a median CIRSG score of 9 (range 0-25). Of these, 31 received various dose-attenuated combination regimens, mostly cyclophosphamide, vincristine and prednisolone (CVP) +/- doxorubicin (CHOP), 6 oral trofosfamide and 5 received other single agent chemotherapy. Median number of cycles for intermittent schedules was 2 (range 1-8). Five pts received additional RT as part of primary treatment and 7 had limited-field RT only. ORR response rate was 47% (95%CI 30-70) and PFS and OS at 3 years 10% (95%CI 2-19) and 12% (95%CI 4-21), respectively (Figure B+D).
Conclusion: BV monotherapy is a tolerated and effective treatment option, and it may improve outcomes compared to conventional therapy in elderly and frail HL patients ineligible for curatively intended combination chemotherapy.