Phase III Study of Daratumumab/rhuph20 (nsc- 810307) + Lenalidomide or Lenalidomide As Post-Autologous Stem Cell Transplant Maintenance Therapyin Patients with Multiple Myeloma (mm) Using Minimal Residual Disease Todirect Therapy Duration (DRAMMATIC study): SWOG s1803

Background:Lenalidomide(Len) maintenance following autologous transplantation(ASCT) for multiple myeloma has improved progression free survival (PFS)and overall survival compared with placebo. Optimal duration of maintenance is unknown with considerable inter-trial variability. Depth of remission correlates with PFS, with patients (pts) in a minimal residual disease negative state (MRD) to a sensitivity of 10 -5 having a better PFS. Therefore, Len combinations that lead to higher MRD negativity rates are under study. The anti CD38 antibody Daratumumab in combination with lenalidomide in newly diagnosed MM pts showed a higher MRD negativity rates in the MAIA trial (NEJM2019). SWOGS1803 is testing this regimen as maintenance following ASCT while also assessing the optimal duration of maintenance in patients who achieve MRD negativity.

Methods:Pts 18-75 years, with MM within 12 months of induction and without progression from diagnosis are eligible. Prior daratumumab therapy is allowed. Enrollment may be before or after ASCT with transplant being within 18 months from initial registration. Within 180 days from ASCT pts will undergo first randomization to Len or Len plus subcutaneous daratumumab/rHuPH20 maintenance (Len Dara). MRD will be assessed prior to start of maintenance and then annually. Randomized treatment will continue for two years at which time repeat MRD will be assessed for pts in VGPR or better. Pts who are MRD negative will undergo second randomization to either continue maintenance on their assigned arm or discontinue maintenance. The continued maintenance arm will stay on therapy for 7 years or until disease progression or unacceptable toxicity.(see schema)

The primary objective of the trial is to compare OS between the two treatment arms (Len vs. LenDara). Secondary objectives include comparisons of overall response rate, PFS, and MRD negativity rate between the treatment arms. The objectives of the second randomization are to compare OS of MRD negative pts who continue maintenance on each arm vs. those who discontinue. An early read out of the trial will be the 24 month MRD analysis after all pts have been accrued. A total of 1100 pts will be accrued to initial step 1 to allow for a 5% drop out and allow 950 pts for the second randomization. As of Aug 1, 171 pts are enrolled for screening among whom 133 have been randomized.