ENRICH

ENRICH is the first randomised trial in untreated mantle cell lymphoma to show that a chemotherapy-free first line beats immunochemotherapy. It ran at 66 sites in the United Kingdom, Sweden, Norway, Finland and Denmark, and randomised 397 patients aged 60 or over with stage II to IV disease and performance status 0 to 2 between ibrutinib 560 mg daily with rituximab, and rituximab with the investigator's pre-chosen chemotherapy, either R-CHOP or bendamustine. All responders received two years of rituximab maintenance every eight weeks; the ibrutinib group continued ibrutinib until progression.

At a median follow-up of 47.9 months, progression-free survival favoured ibrutinib-rituximab with an adjusted hazard ratio of 0.69 (95 per cent confidence interval 0.52 to 0.90, p = 0.0034). The subgroup split is the interesting part: against R-CHOP the hazard ratio was 0.37 (0.22 to 0.62), against bendamustine-rituximab 0.91 (0.66 to 1.25). Grade 3 or above adverse events were reported by 67 per cent of the ibrutinib-rituximab group and 70 per cent of the immunochemotherapy group.

The practical reading is that the chemotherapy-free option is clearly better than R-CHOP and roughly equivalent to bendamustine-rituximab, which is why it is an option rather than a replacement. The median age was 74 and three-quarters of participants were male, which matches the epidemiology of the disease.