MRD-driven therapeutic strategies in multiple myeloma
| Study . | Official title . | Phase . | Patient population . | Point of MRD-driven decisions . | MRD-driven therapeutic strategies . | MRD evaluation technique . |
|---|---|---|---|---|---|---|
| IFM 2020-02 NCT04934475 | Minimal Residual Disease Adapted Strategy (MIDAS) | 3 | NDMM, TE | Post–Isa-KRd induction. | Randomization to various consolidation pathways based on MRD status. | NGS at 10−6 sensitivity |
| PERSEUS NCT03710603 | Daratumumab, VELCADE (Bortezomib), Lenalidomide, and Dexamethasone Compared with VELCADE, Lenalidomide, and Dexamethasone in Subjects With Previously Untreated Multiple Myeloma (Perseus) | 3 | NDMM, TE | Upon sustained MRD negativity for 12 mo and at MRD relapse. | Cessation of dara upon sustained 12-mo MRD negativity then reintroduction of dara upon MRD relapse. | NGS at 10−5 sensitivity |
| MASTER NCT03224507 | Monoclonal Antibody–Based Sequential Therapy for Deep Remission in Multiple Myeloma (MASTER) | 2 | NDMM, TE | Upon achieving post-ASCT MRD negativity. | Entry into treatment-free observation and MRD surveillance phase upon achieving post–ASCT MRD negativity. | NGS at 10−5 sensitivity |
| REMNANT NCT04513639 | Relapse From MRD Negativity as Indication for Treatment (REMNANT) Study | 3 | Patients with MRD negativity after VRd induction before and consolidation after ASCT. | Upon MRD relapse (loss of MRD negativity). | Randomization to receive second-line treatment (KRd) either at loss of MRD-negative CR or at progressive disease, per IMWG criteria. | NGF at 10−5 sensitivity |
| DRAMMATIC/S1803 NCT04071457 | S1803, Lenalidomide ± Daratumumab/rHuPh20 as Post–ASCT Maintenance for MM w/MRD to Direct Therapy Duration (DRAMMATIC) | 3 | TE | After 2 y of maintenance (R ± dara) post–ASCT. | Patients who are MRD positive continue assigned therapy. Those who are MRD negative are randomly assigned to continue or discontinue therapy. | NGS |
| AURIGA NCT03901963 | A Study of Daratumumab Plus Lenalidomide Versus Lenalidomide Alone as Maintenance Treatment in Participants With Newly Diagnosed Multiple Myeloma Who Are Minimal Residual Disease Positive After Frontline Autologous Stem Cell Transplant (AURIGA) | 3 | Patients who are MRD positive after ASCT ± consolidation. | After ASCT ± consolidation. | Patients who are MRD positive will be randomly assigned to receive R, with or without dara. | NGS at 10−5 sensitivity |
| PREDATOR - MRD NCT03697655 | Pre-emptive Daratumumab Therapy of Minimal Residual Disease Reappearance or Biochemical Relapse in Multiple Myeloma (PREDATOR) | 2 | MRD-negativity patients after 1 or 2 prior lines of therapy. | At MRD relapse (loss of MRD-negativity). | Patients with MRD negativity who experience MRD relapse will be given dara. | NGF at 10−5 sensitivity |
| CONPET NCT03314636 | Intensified Treatment With Carfilzomib in Myeloma Patients Still PET-positive After First Line Treatment. (CONPET) | 2 | TIE and TE patients after 1 L of therapy. | Post 1 L of therapy. | Patients who are PET negative will be excluded from treatment; those who are PET positive will be given KRd. | PET/CT NGF at 10−5 sensitivity. |
| NCT04221178 | Stopping Maintenance Therapy in People With Multiple Myeloma in MRD-Negative Remission | — | Patients with NDMM or RRMM who have sustained MRD negativity for at least 3 y while receiving continuous maintenance therapy. | Upon sustained MRD negativity for 3 y. | Cessation of continuous maintenance therapy upon sustained MRD negativity for at least 3 y. | NGF at 10−5 sensitivity. |
| Study . | Official title . | Phase . | Patient population . | Point of MRD-driven decisions . | MRD-driven therapeutic strategies . | MRD evaluation technique . |
|---|---|---|---|---|---|---|
| IFM 2020-02 NCT04934475 | Minimal Residual Disease Adapted Strategy (MIDAS) | 3 | NDMM, TE | Post–Isa-KRd induction. | Randomization to various consolidation pathways based on MRD status. | NGS at 10−6 sensitivity |
| PERSEUS NCT03710603 | Daratumumab, VELCADE (Bortezomib), Lenalidomide, and Dexamethasone Compared with VELCADE, Lenalidomide, and Dexamethasone in Subjects With Previously Untreated Multiple Myeloma (Perseus) | 3 | NDMM, TE | Upon sustained MRD negativity for 12 mo and at MRD relapse. | Cessation of dara upon sustained 12-mo MRD negativity then reintroduction of dara upon MRD relapse. | NGS at 10−5 sensitivity |
| MASTER NCT03224507 | Monoclonal Antibody–Based Sequential Therapy for Deep Remission in Multiple Myeloma (MASTER) | 2 | NDMM, TE | Upon achieving post-ASCT MRD negativity. | Entry into treatment-free observation and MRD surveillance phase upon achieving post–ASCT MRD negativity. | NGS at 10−5 sensitivity |
| REMNANT NCT04513639 | Relapse From MRD Negativity as Indication for Treatment (REMNANT) Study | 3 | Patients with MRD negativity after VRd induction before and consolidation after ASCT. | Upon MRD relapse (loss of MRD negativity). | Randomization to receive second-line treatment (KRd) either at loss of MRD-negative CR or at progressive disease, per IMWG criteria. | NGF at 10−5 sensitivity |
| DRAMMATIC/S1803 NCT04071457 | S1803, Lenalidomide ± Daratumumab/rHuPh20 as Post–ASCT Maintenance for MM w/MRD to Direct Therapy Duration (DRAMMATIC) | 3 | TE | After 2 y of maintenance (R ± dara) post–ASCT. | Patients who are MRD positive continue assigned therapy. Those who are MRD negative are randomly assigned to continue or discontinue therapy. | NGS |
| AURIGA NCT03901963 | A Study of Daratumumab Plus Lenalidomide Versus Lenalidomide Alone as Maintenance Treatment in Participants With Newly Diagnosed Multiple Myeloma Who Are Minimal Residual Disease Positive After Frontline Autologous Stem Cell Transplant (AURIGA) | 3 | Patients who are MRD positive after ASCT ± consolidation. | After ASCT ± consolidation. | Patients who are MRD positive will be randomly assigned to receive R, with or without dara. | NGS at 10−5 sensitivity |
| PREDATOR - MRD NCT03697655 | Pre-emptive Daratumumab Therapy of Minimal Residual Disease Reappearance or Biochemical Relapse in Multiple Myeloma (PREDATOR) | 2 | MRD-negativity patients after 1 or 2 prior lines of therapy. | At MRD relapse (loss of MRD-negativity). | Patients with MRD negativity who experience MRD relapse will be given dara. | NGF at 10−5 sensitivity |
| CONPET NCT03314636 | Intensified Treatment With Carfilzomib in Myeloma Patients Still PET-positive After First Line Treatment. (CONPET) | 2 | TIE and TE patients after 1 L of therapy. | Post 1 L of therapy. | Patients who are PET negative will be excluded from treatment; those who are PET positive will be given KRd. | PET/CT NGF at 10−5 sensitivity. |
| NCT04221178 | Stopping Maintenance Therapy in People With Multiple Myeloma in MRD-Negative Remission | — | Patients with NDMM or RRMM who have sustained MRD negativity for at least 3 y while receiving continuous maintenance therapy. | Upon sustained MRD negativity for 3 y. | Cessation of continuous maintenance therapy upon sustained MRD negativity for at least 3 y. | NGF at 10−5 sensitivity. |
Clinical trials were selected based on a search of http://clinicaltrials.gov, as of July 2021.
ASCT, autologous stem cell transplant; CT, computed tomography; D, dexamethasone; dara, daratumumab; isa, isatuximab; K, carfilzomib; KRd, carfilzomib-lenalidomide-dexamethasone; L, line; NDMM, newly diagnosed multiple myeloma; PET, positron emission tomography; R, lenalidomide; TE, transplant eligible; TIE, transplant ineligible; V, bortezomib; VRd; bortezomib-lenalidomide-dexamethasone.