Excellent survival after R-Hyper-CVAD in hospitalized patients with high-risk large B-cell lymphoma: The Karolinska experience

Patients with high-risk aggressive B-cell lymphoma exhibit poor survival after R-CHOP. More intensive regimens yield higher rates of remission but also of complication. We investigated all 401 patients < 70 years with high-risk (age-adjusted [aa] international prognostic index [IPI] ≥2, extranodal, or bulky) aggressive B-cell lymphoma hospitalized at Karolinska for urgent start of immunochemotherapy (129 R-Hyper-CVAD; 261 R-CHOP/R-CHOEP). Patients showed IPI 3-5 (70%), WHO PS ≥2 (49%), bulky disease (70%), extranodal (75%) and CNS (8%) involvement. Five-year overall/progression-free survival (OS/PFS) was better in patients who started R-Hyper-CVAD (84%/77%) compared with R-CHOP/R-CHOEP (66%/55%). Differences were independent in multivariable analysis, seen in all patient categories, and accentuated in extreme high-risk disease: R-Hyper-CVAD vs. R-CHOP/R-CHOEP showed 5-year PFS 69% vs.40% in aaIPI 3 and 88% vs. 38% in CNS involvement. For validation, survival was compared between the two Karolinska sites and calendar periods. Survival was superior 2006-2010 at the site that introduced R-Hyper-CVAD/R-MA 2006, identical at both sites 2011-2017 after the other site adopted R-Hyper-CVAD/R-MA 2011, and excellent 2018-2020 when R-Hyper-CVAD/R-MA use increased to 75% of patients. Despite considerable toxicity, also patients aged 61-69 years showed better survival with R-Hyper-CVAD/R-MA. This is the largest single-centre series of patients treated with R-Hyper-CVAD/R-MA, showing favourable outcome in high-risk aggressive B-cell lymphoma.