Mantle cell lymphoma: is it time for risk-adapted treatment?
Mené sur 267 patients atteints d'un lymphome à cellules du manteau récidivant ou réfractaire (durée médiane de suivi : 51,2 mois ; 21 % de femmes), cet essai randomisé international de phase III évalue l'efficacité, du point de vue de la survie sans progression, et la sécurité de l'association ibrutinib–vénétoclax par rapport à l'ibrutinib seul
The unmet need for new mantle cell lymphoma (MCL) treatment is evident since it is non-curable and the rate of relapse is high. Therefore, initiatives investigating new treatment options, such as the SYMPATICO study by Michael Wang and colleagues, are highly interesting. Current treatments cause various toxicities, including multiple delayed effects, particularly neutropenia, infections, and secondary cancers. Patients with MCL are usually older (median age 71 years) and many have a high burden of comorbidities making it even more difficult for them to tolerate the treatment. In the BOVen first-line trial, zanubrutinib, obinotuzumab, plus venetoclax showed promising efficacy, with an overall response rate of 96% in patients with TP53 mutations, a well known adverse prognostic factor in MCL. This drug combination has been incorporated as a valid treatment option in some countries. The SYMPATICO study also supported use of similar drug combinations in patients with MCL in first-line treatment and at relapse. However, it has not been recommended in previous studies to use similar combinations with ibrutinib (or other Bruton tyrosine kinase inhibitors) and venetoclax in all patients, including those with low risk. In SYMPATICO, 112 (84%) of 134 patients in the ibrutinib–venetoclax group had grade 3 or worse overall and fatal adverse events, which is a high rate for a low-risk group. Furthermore, studies have shown a high rate of neutropenia in treatment combinations including venetoclax, such as in the VALERIA trial in which a combination with lenalidomide was used.
The Lancet Oncology 2024