Functional imaging to complement bone marrow MRD in multiple myeloma

Extramedullary disease and “skeletal escape” can have a high incidence in patients with late relapse or who receive immunotherapy [1], which poses an issue for bone marrow assessments of minimal residual disease (MRD). Dr Elena Zamagni (Bologna University, Italy) discussed functional imaging as an alternative or complementary technique to bone marrow MRD for multiple myeloma assessment [1].

In clinical trials and real-life studies, fluorodeoxyglucose-F-18 (FDG)-PET/CT has been used to assess MRD status and metabolic response to therapy and has been shown to be complementary to bone marrow flow cytometry [1].

Using the Deauville criteria (score 1–3), PET complete metabolic response following therapy was defined for MRD negativity as uptake ≤ liver activity in bone marrow sites and previously involved focal lesions (including extramedullary and paramedullary disease) [2]. Definitions based on Deauville scores 4­5 corresponded to partial metabolic responses. These response definitions were further validated using data from the FORTE phase 2 trial showing that PET/CT-derived complete metabolic response is complementary to multiparameter bone marrow flow cytometry [3]. Updated definitions for plasmacytoma response by PET/CT are currently under evaluation and should be published in 2024 [1]. But is PET/CT useful during follow-up of first-line treatment? In Dr Zamagni’s opinion, PET/CT follow-up should be performed for all patients with a Deauville score of at least 4 [1].

However, what can be done in patients who are PET/CT negative at baseline? Or what alternative technique can be used? Diffusion-weighted whole-body MRI (DWI/MRI) is a potential alternative to PET/CT. In a retrospective analysis of participants who received autologous stem cell transplant (ASCT) for newly diagnosed multiple myeloma, DWI/MRI detected more participants with residual focal lesions compared with PET/CT [4]. Furthermore, univariate and multivariate analyses showed that DWI/MRI is complementary to bone marrow flow cytometry, and that imaging-detected residual focal lesions are independent risk factors for negative outcomes post-ASCT [4].

One question that remains is whether treatment decisions can be tailored using imaging-derived MRD [1]. The phase 2 CONPET trial enrolled participants with very good partial response or better after ASCT, and participants with PET-positive disease received KRd maintenance. Following therapy, 33% of participants converted from PET-positive to PET-negative disease indicating that imaging could be a potential tool for informing treatment decisions [5].

In summary, Dr Zamani reinforced that imaging is a mandatory tool recommended by guidelines for MRD evaluation following therapy, with FDG-PET/CT as the more available and established technique. Currently, DWI/MRI is an emerging technique. Furthermore, imaging is complementary to bone marrow techniques and is commonly used as a secondary endpoint in clinical trials. However, although these imaging techniques appear effective in small studies, treatment can’t be yet tailored based on imaging studies only.

1. Zamagni E. Imaging vs BM MRD: When and how? Session III: MRD in clinical trials and application challenges in clinical practice. EMN 2024, 18–20 April, Turin, Italy.
2. Zamagni E, et al. J Clin Oncol. 2021;39(2):116-125.
3. Zamagni E, et al. EClinicalMedicine. 2023:60:102017.
4. Shincke C, et al. Blood. 2023;142(Supplement 1): 882.
5. Norgaard JN, et al. Leukemia. 2023;37(10):2107-2114.

Medical writing support was provided by Mihai Surducan, PhD.

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Posted on 22 April 202422 April 2024