The REMNANT study: will treatment at MRD relapse improve survival in MM?

Dr Frida Bugge Askeland, associated research doctor and PhD student at the Oslo Myeloma Center in Norway outlined the REMNANT study.

The REMNANT study aims to assess whether addressing MRD relapses following initial treatment enhances PFS and OS in myeloma patients.

The clinical design of this phase 2/3 study involves 400 transplant-eligible MM patients undergoing standard of care treatment in part 1. This treatment comprises four pre-transplant induction and four post-transplant consolidation cycles of bortezomib, lenalidomide, and dexamethasone (VRd). After induction, patients undergo either tandem or single transplant. All patients receive lenalidomide maintenance, the sole approved and reimbursed therapy in Norway. The inclusion criteria are extensive, encompassing patients with kidney failure, amyloidosis, plasma cell leukaemia and other comorbidities.

MRD is evaluated using flow cytometry with a sensitivity of 10^-5 at diagnosis and post-consolidation in the first line. Patients achieving CR MRD status post-consolidation proceed to part 2 of the study, while others are monitored for 24 months on lenalidomide maintenance and join part 2 upon attaining MRD negativity.

Part 2 constitutes the randomized segment, wherein 176 patients receive second-line treatment at either loss of CR or MRD negativity or PD. In the MRD-guided experimental arm, MRD negativity is assessed every four months.

Data currently available pertains only to part 1, focusing on standard treatment. In first-line treatment, an ORR of 98% was observed, with 55% of patients achieving an MRD-negative complete response. Bortezomib was initially administered twice weekly during first-line treatment, but nearly half of the patients had to discontinue prematurely due to neuropathy. Consequently, the protocol was modified after 200 patients to administer bortezomib once a week, facilitating a later comparison of side effects and efficacy.

Given the significance of MRD for prognosis and the incurable nature of MM, ongoing trials exploring MRD status as a guide for treatment intensification or de-escalation are crucial. Definitive conclusions are pending the completion of these trials.

Currently, there is no conclusive outcome of the REMNANT study, as this will be derived from the second part.

Reference:

Askeland F, ASH2023. #4755

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