Background: Outcomes in the growing group of older patients (pts) with advanced-stage classical Hodgkin lymphoma (cHL) are historically poor.
Methods: The international GHSG-NLG intergroup phase II BVB trial (NCT02191930) evaluated six cycles of brentuximab vedotin (1.8mg/kg), cyclophosphamide (750mg/m2), doxorubicin (50mg/m2) and prednisone (100mg/day 2-6; B-CAP) as first-line treatment for advanced-stage cHL pts ≥60 years considered eligible for polychemotherapy. Primary endpoint was objective response rate (ORR) by computed tomography (CT) after at least 2 cycles. Secondary endpoints included feasibility, toxicity, progression-free (PFS) and overall survival (OS).
Results: With a median follow-up of 35 months, 49 pts with a median age of 66 years (range: 60-84) were evaluable in the intention-to-treat population. The majority presented with ECOG performance status 1 (61%, range 1-3), stage IV HL (65%), international prognostic score ≥4 (50%), and CIRS-G score 1-3 (51%, range 0-7).
Six cycles were administered in 46/49 pts (94%). Three pts terminated treatment early due to toxicity, including one infection-related death before response assessment. With G-CSF support in 98% of pts, the maximum dose level was maintained in 86% of pts, and the mean relative dose intensity was 93%. Most pts experienced hematological toxicities (any grade [G]: 92%, G3: 8%, G4: 53%); i.e. neutropenia (G3/4: 61%), anemia (G3/4: 18%) and thrombocytopenia (G3/4: 10%). Febrile neutropenia occurred in 27% and infections in 61% (G3: 29%, G4: 2%, G5: 2%) of pts, respectively. Neuropathy was mostly sensory and reported in 67% of pts (G2: 20%, no ≥G3). CT-based ORR after 2 and 6 cycles were 94% (CR: 34%) and 98% (CR: 44%, 95%CI: 90.5-100). Positron emission tomography (PET) after the last cycle showed metabolic CR in 31/48 pts (65%). Ten patients (20%) received consolidative 30 Gy radiotherapy to PET+ residues. Overall, 16 patients (33% of) experienced tumor progression or relapse and 9 (18%) died, mostly from cHL (n=6, 12%). 3-year PFS and OS are 64% (95%CI: 50-79, Figure 1A+B) and 91% (95%CI: 82-99), with improved 3-year PFS observed in patients achieving a metabolic CR (82%) compared to pts with metabolic PR (33%; Figure 1C+D).
Conclusions: B-CAP is a feasible and effective treatment option for older patients with advanced-stage cHL, with high response rates already after 2 cycles and improved 3-year PFS in patients achieving a metabolic CR