Table 1.
Clinical trials where MRD guides treatment decisions. Results are based on a search in the ‘https://clinicaltrials.gov/’ website that included the terms “multiple myeloma” and “MRD”, and individual identification of clinical trials where treatment algorithms were triggered by patients’ MRD status. Selected studies (identified with an asterisk) were added based on knowledge of their existence, despite being absent in search results. It should be noted that many more studies assess MRD and in most clinical trials, MRD response rates are a primary or secondary endpoint (see Fig. 1). However, because no apparent treatment decision is being made based on patients’ MRD status, those studies were not included in the table below. There are many clinical trials that, to the best of our knowledge, will have MRD-guided treatment decisions but were not added because their design is still being finalized or have not been initiated at the time of this publication
| NCT | Study official title | Country | Technique |
|---|---|---|---|
| NCT02406144 | Maintenance treatment with lenalidomide and dexamethasone versus lenalidomide, dexamethasone and ixazomib after autologous hematopoietic stem cell transplantation in patients With newly diagnosed symptomatic multiple myeloma-duration of maintenance guided by MRD status (GEM2014MAIN) | Spain | NGF |
| RADAR* | Risk adapted therapy directed according to response comparing treatment escalation and de-escalation strategies in newly diagnosed patients with multiple myeloma suitable for stem cell transplantation | UK | N/A |
| NCT03490344 | Short course daratumumab in minimal residual disease (MRD) positive myeloma patients after induction therapy with/without consolidative high-dose chemotherapy/autologous stem cell support | USA | FC |
| NCT03224507 | Monoclonal antibody-based sequential therapy for deep remission in multiple myeloma (MASTER) | USA | NGS |
| NCT03742297* | Induction therapy with bortezomib-melphalan and prednisone (VMP) followed by lenalidomide and dexamethasone (Rd) versus carfilzomib, lenalidomide, and dexamethasone (KRd) plus/minus daratumumab, 18 cycles, followed by consolidation and maintenance therapy with lenalidomide and daratumumab: phase III, multicenter, randomized trial for elderly fit newly diagnosed multiple myeloma patients aged between 65 and 80 years | Spain | NGF |
| NCT03697655 | Pre-emptive daratumumab therapy of minimal residual disease reappearance or biochemical relapse in multiple myeloma (PREDATOR) | Poland | N/A |
| NCT03710603 | A phase 3 study comparing daratumumab, VELCADE (Bortezomib), lenalidomide, and dexamethasone (D-VRd) vs VELCADE, lenalidomide, and dexamethasone (VRd) in subjects with previously untreated multiple myeloma who are eligible for high-dose therapy (PERSEUS) | EMN | N/A |
| NCT03992170 | A pilot study on the efficacy of daratumumab in multiple myeloma (MM) patients in >VGPR/MRD-positive by next-generation flow (DART4MM) | Italy | FC |
| NCT02969837 | Open-label, single-arm, phase 2 study of initial treatment with elotuzumab, carfilzomib (Kyprolis), lenalidomide (Revlimid), and low-dose dexamethasone (E-KRd) in newly diagnosed, multiple myeloma requiring systemic chemotherapy | USA | NGS and MFC |
| NCT04071457 | S1803, phase III study of daratumumab/rHuPH20 (NSC-810307) + lenalidomide or lenalidomide as post-autologous stem cell transplant maintenance therapy in patients with multiple myeloma (MM) using minimal residual disease to direct therapy duration (DRAMMATIC study) | USA | NGS |
| NCT04096066 | Carfilzomib-lenalidomide-dexamethasone (KRd) versus lenalidomide-dexamethasone (Rd) in newly diagnosed myeloma patients not eligible for autologous stem cell transplantation: a randomized phase III trial | Italy | N/A |
| NCT03376477 | A randomized, double-blind, placebo-controlled phase II trial of an allogeneic myeloma GM-CSF vaccine with lenalidomide in multiple myeloma patients in complete or near complete | USA | NGS |
| NCT04108624 | A multimodality approach to minimal residual disease detection to guide post-transplant maintenance therapy in multiple myeloma (MRD2STOP) | USA | NGS |
| NCT04221178 | A single-arm, prospective atudy of maintenance therapy cessation for patients with multiple myeloma in sustained MRD-negative remissions | USA | NGF |
| NCT04140162 | Phase 2 study with minimal residual disease (MRD) driven adaptive strategy in treatment for newly diagnosed multiple myeloma (MM) with upfront daratumumab-based therapy | USA | N/A |
NGS next-generation sequencing, FC flow cytometry, NGF next-generation flow cytometry, N/A not available, EMN European Myeloma Network