This study is designed as a multicenter, randomized, parallel groups, open-label, phase 3 study in subjects with untreated newly diagnoses Multiple Myeloma eligible for ASCT.
824 patients will be enrolled in this study from approximately 70 study sites.
The 2 parts in the Treatment Phase are described below.
Part 1: Induction/ASCT/Consolidation Phase (1:1 Randomization)
After the screening period, patients will be randomly allocated (1:1) to either:
* Arm A (standard of care arm): standard induction therapy with 4 cycles of D-VRd, followed by HDCT (Melphalan) + ASCT, D-VRd consolidation therapy * Arm B (experimental arm): standard induction therapy with 4 cycles of D-VRd, followed by elranatamab and lenalidomide consolidation therapy.
Part 2: Maintenance Phase (1:1 Re-randomization) Patients will be re-randomized (1:1) and will enter the Maintenance Phase upon completion of consolidation therapy.
• Arm C (standard of care arm): daratumumab + lenalidomide approx 2 years. Subjects with a negative MRD (for at least 12 months) after 24 cycles of daratumumab-lenalidomide will discontinue daratumumab and continue with lenalidomide monotherapy until disease progression, or study cut-off date (whichever occurs first).
Subjects who did not achieve MRD negativity for at least 12 months after 24 cycles of daratumumab-lenalidomide will continue to receive daratumumab-lenalidomide until:
* MRD negativity for at least 12 months is reached. Subjects will then continue with lenalidomide monotherapy until disease progression, or study cut-off date (whichever occurs first). * Disease progression * Or study cut-off date (whichever occurs first).
* Arm D (experimental arm): elranatamab. Approx 2 years. Subjects with a negative MRD (for at least 12 months) after receiving M22 administration of elranatamab will discontinue study treatment with elranatamab.
Subjects who did not achieve MRD negativity for at least 12 months after M22 elranatamab administration will continue to receive elranatamab, every 24 weeks, until MRD negativity for at least 12 months is reached, disease progression, or study cut-off date (whichever occurs first).
Male or female subjects, aged over 18 but < 70 years old
Patients have provided voluntary written informed consent before performing any study-related procedure.
Patients with newly diagnosed multiple myeloma (NDMM) eligible for high-dose chemotherapy (melphalan) and autologous stem cell transplantation (ASCT).
More than 1 focal lesion (≥5 mm diameter) on MRI.
Subjects previously treated with any systemic therapy for multiple myeloma. Patients are allowed corticosteroids before or during screening, as far as the total dose received is not >160 mg of dexamethasone (or equivalent) within 14 days before initiating induction therapy. Patients with concurrent radiotherapy within the 14 days before initiating induction therapy are not eligible (If possible, in these cases, enrolment should be deferred).
Subject with ongoing Grade ≥ 3 peripheral sensory or motor neuropathy.
Subject with history of GBS or GBS variants, or history of any Grade ≥3 peripheral motor polyneuropathy.
Subject with a current diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, or solitary plasmacytoma.
Intergroupe Francophone du Myelome
Lead sponsor
Pfizer
Collaborator