Immunotherapy for older patients with classic Hodgkin lymphoma
Mené sur 46 patients atteints d'un lymphome hodgkinien et âgés de plus de 60 ans (âge médian : 71,5 ans) ou inéligibles à une chimiothérapie (âge : inférieur à 60 ans), cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse globale, et la toxicité d'un traitement de première ligne combinant brentuximab védotin et nivolumab (durée médiane de suivi : 21,2 mois)
In The Lancet Haematology, a team led by Bruce Cheson reports on using a combination of two recently developedimmunological drugs, the antibody-drug conjugate brentuximab vedotin and the checkpointinhibitor nivolumab, to treat classic Hodgkin lymphoma in a special population: patientswho are too frail to be treated safely with standard cytotoxic chemotherapy. They chose this combination for sound reasons. Patients with classic Hodgkin lymphomawho, because of age or organ dysfunction, cannot be safely treated with a standardregimen, such as doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), haveworse outcomes than those seen in fitter patients, and they have a major unmet needfor more effective, safer treatment. Brentuximab vedotin is directed against CD30, which is ubiquitously expressed inthe malignant cells of classic Hodgkin lymphoma, and the drug is highly efficaciousfor both relapsed and previously untreated classic Hodgkin lymphoma. Nivolumab targets and neutralises programmed death-1 protein, thus undoing the classicHodgkin lymphoma-associated blockage of a patient's ability to mount an immune attackon classic Hodgkin lymphoma cells. It is also highly effective against relapsed and newly diagnosed classic Hodgkin lymphoma. Both drugs have modest, non-overlapping toxicity, and can be tolerated in fully effectivedoses even by frail patients. Hoping that the combination would be even more effective than either drug alone,the investigators set a very high bar for success: an overall response rate of 80%.Disappointingly, at the planned interim analysis, when 25 patients could be evaluatedfor response, the combination fell short of that, producing an overall response rateof 64% (95% CI 43–82), and the trial was closed. Because accrual had continued whilethe first 25 evaluable patients completed treatment and were assessed, 46 patientswere ultimately treated, of whom 28 (61%) responded. The promising combination failedto be effective enough to justify further evaluation.
The Lancet Haematology , commentaire, 2019