Phase 2 LYSA study of prednisone, vinblastine, doxorubicin, bendamustine for untreated older Hodgkin lymphoma patients.

Older classical Hodgkin lymphoma (cHL) patients require more effective and less toxic therapies. In this multicenter, prospective, phase 2 study, we investigated a new first-line therapy regimen comprising 6 cycles of prednisone (40 mg/m2 Day 1-5), vinblastine (6 mg/m2, Day 1), doxorubicin (40 mg/m2, Day 1), bendamustine (120 mg/m2, Day 1) (PVAB regimen) every 21 days for newly diagnosed classical HL patients aged 61 years or older with an advanced Ann Arbor stage. A Mini Nutritional Assessment (MNA) score ≥ 17 was the cutoff value for including patients ≥70 years old. The primary endpoint was the complete metabolic response (CMR) rate after 6 cycles. The median age of the 89 included patients was 68 years (range, 61-88), with 35 patients aged ≥70 years old (39%). Seventy-eight patients (88%) completed the 6 cycles. The toxicity rate was acceptable, with a 20% rate of related serious adverse events. CMR was achieved by 69 patients (77.5%; 95% CI, 67-86). After a median follow-up of 42 months, 31 patients progressed or relapsed (35%), and 24 died (27%) from HL (n=11), toxicity during treatment (n=4), secondary cancers (n=6), or other causes (n=3). The 4-year progression-free survival (PFS) and overall survival rates were 50% and 69%, respectively. Multivariate analysis showed that liver involvement (P =0.001), lymphopenia (P =0.001), CRP (P =0.0005), comedications (P =0.003) were independently associated with PFS. The PVAB regimen yielded a high CMR rate with acceptable toxicity. Over long-term follow-up, survival endpoints were influenced by unrelated lymphoma events. Registration at www.clinicaltrials.gov was NCT02414568.