Abstract P081

Brentuximab vedotin, Cyclophosphamide, Doxorubicin and Prednisone (B-CAP) First-Line Treatment of Advanced-Stage Hodgkin Lymphoma: Final Results of the GHSG-NLG Phase II BVB Trial

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

Authors

Paul J. Bröckelmann, Boris Böll, Daniel Molin, Gundolf Schneider, Sirpa M. Leppä, Julia Meissner, Peter Kamper, Martin Hutchings, Jacob Haaber Christensen, Ulf Schnetzke, Michael Fuchs, Dennis A. Eichenauer, Bastian von Tresckow, Helen Kaul, Peter Borchmann, Alexander Fossa