FDA Approval Summary: Selinexor for Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Cette étude analyse les données de l'essai ayant conduit la "Food and Drug Administration" à autoriser l'utilisation du sélinexor pour traiter les patients atteints d'un lymphome diffus à grandes cellules B réfractaire ou récidivant
In June 2020, the FDA granted accelerated approval to selinexor for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. Approval was based on SADAL, a multicenter trial of selinexor monotherapy in patients with DLBCL after 2 to 5 systemic regimens. Efficacy was based on independent review committee-assessed objective response rate (ORR) and duration of response using Lugano criteria. In 134 patients treated with the approved dosage (60 mg orally on Days 1 and 3 of each week), the ORR was 29% (95% CI, 22-38), with complete response in 13% and 38% of responses lasting at least 6 months. Gastrointestinal toxicity developed in 80% of patients, hyponatremia in 61%, central neurological toxicity (such as dizziness and mental status changes) in 25%, and ocular toxicity in 18%. New or worsening Grade 3 or 4 thrombocytopenia, lymphopenia, neutropenia, anemia, or hyponatremia developed in ≥15%. Adverse reactions led to selinexor dose interruption in 61% of patients, dose reduction in 49%, and permanent discontinuation in 17%, with thrombocytopenia being the leading cause of dose modifications. Post-marketing studies will evaluate reduced dosages of selinexor and further evaluate clinical benefit in patients with relapsed or refractory DLBCL. Implications for Practice Selinexor is a new potential option for adults with relapsed or refractory DLBCL NOS in the third-line setting or beyond. Toxicities are typically manageable, but can be difficult to tolerate and necessitate close monitoring and supportive care.
The Oncologist 2021