Positive FDA AdCom vote on MRD as AA endpoint in multiple myeloma

The US Food and Drug Administration’s (FDA) oncology drugs advisory committee (ODAC) voted 12-0 to endorse the use of minimal residual disease (MRD) at 10-5 in complete responders (CR) as an intermediate endpoint for accelerated approval, potentially opening the door to new trial designs for blood cancer drugs.

University of Miami Sylvester Comprehensive Cancer Center led EVIDENCE team ( presentation), International Independent Team for Endpoint Approval of Myeloma Minimal Residual Disease (i2TEAMM, presentation), and FDA ( presentation) presented meta-analyses of association of MRD-negativity to survival outcomes at the individual and trial levels.

The association meta-analyses were completed prior to the CAR-T / TCE era. The FDA was circumspect in its comments around the applicability to CAR-T. In other settings, the FDA did not extend the applicability of an intermediate endpoint from therapeutic class to another (eg, HER2-targeted therapies to checkpoint inhibitors in use of pathologic complete response in neo-adjuvant breast cancer for that ODAC discussion)