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.