The Next Step for MRD in Myeloma? Treating MRD Relapse after First Line Treatment in the REMNANT Study

Abstract

The treatment approach for multiple myeloma (MM) has changed in recent years. After the approval of maintenance treatment after stem cell transplant in younger patients, the paradigm of continuous treatment is now prevailing in all clinical situations of myeloma. However, the best time to initiate relapse treatment is still unclear. With increased frequency of minimal residual disease (MRD) negativity, and the established clinical benefit of this finding, one of the large clinical questions in myeloma is how to approach MRD re-appearance. In this paper, we go through the MRD technology, existing and possible uses of MRD in the clinic, and data for early treatment before we introduce the design of the ongoing REMNANT study; a randomized study with early treatment of MRD relapse after first line treatment.

Lymphoplasmacytic variant of multiple myeloma

“…The patient was treated with initial radiation therapy. He was included in an ongoing study protocol for MM [ 1 ], where he received induction therapy with bortezomib, lenalidomide, and dexamethasone (Bort‐Len‐Dex‐regimen) repeated for four cycles. He was withdrawn from the study because of progressive disease with increasing kappa light chains and he quickly went to double autologous stem cell transplantation.…”

Measurable Residual Disease Assessment in Multiple Myeloma: How Deep Is Enough?

“…Treatment intervention upon signs of biochemical relapse rather than clinical symptoms can have a favorable impact on the outcome of these patients, as observed by the ENDEAVOR trial [148]. The hypothesis that outcome could be improved when considering an even lower level of disease, as determined by MRD assessment, is being addressed in the ongoing REMNANT trial (NCT04513639), where MRD negative patients after induction are randomized to start treatment if MRD becomes positive versus at the time of progressive disease [149].…”

Minimal residual disease in multiple myeloma: why, when, where

“…The REMNANT study (NCT04513639) will help answer this ques tion. 74 Patients who are MRD neg a tive after induc tion ther apy are ran dom ized to start treat ment at the time of MRD relapse vs at the time of pro gres sive dis ease according to IMWG cri te ria. However, a lim i ta tion in treating patients for relapse by MRD cri te ria is that cur rent clin i cal tri als gen er ally require mea sur able dis ease, and MRD pos i tiv ity is not con sid ered mea sur able to be eli gi ble for the trial.…”