Professor Jesus San Miguel chaired the Disease Monitoring session and discussed the most important data in the field. Speakers and members of the panel included: Professors Brian Durie, Irene Ghobrial, Shaji Kumar, Andrew Spencer, Saad Usmani and Andrew Yee. There are several unanswered questions that were discussed in this session, including the best imaging technique for the definition of minimal residual disease (MRD), the role of MRD in changing treatment decisions, the innovation of mass spectrometry for the improvement of disease response and the importance of immune reconstitution for myeloma prognosis.
Professor Jens Hillengass presented on the importance of imaging to assess spatial heterogeneity in myeloma and discussed the prognostic significance of imaging after therapy, which is complementary to MRD assessment. PET/CT is the best technique to date for the definition of imaging MRD negativity and is widely available. However, Diffusion-Weighted Imaging (DWI) MRI is more sensitive, and it may substitute PET/CT soon. Modern techniques including radiogenomics by IT-supported image analysis might improve clinical and research applications.
Dr. Tom Martin discussed the possibility of treatment discontinuation, intensification or initiation of a new therapy based on MRD results. He firstly showed that the achievement of MRD negativity at any point was associated with improved PFS versus persistent MRD positivity in newly diagnosed myeloma patients who receive frontline therapy. Although there is some evidence that suggests MRD is useful in guiding clinical decisions during initial therapy and has a positive impact on PFS, this role remains to be confirmed in prospective, randomized clinical trials.
In subsequent oral presentations, Dr. Mattia D’Agostino presented data from the FORTE trial where MRD-negative patients with amp(1q), high circulating tumor cells or multiple high-risk cytogenetic abnormalities were at high risk of losing their MRD-negative status over time. During the exposure to carfilzomib and lenalidomide maintenance, patients were at lower risk of losing the MRD-negative status versus those on maintenance with lenalidomide alone. Dr. Bruno Paiva showed that patients achieving early and sustained MRD-negativity after ide-cel CAR-T cell therapy have prolonged PFS. This study also uncovered a high frequency of hemodilution in bone marrow aspirates after CAR-T therapy, and the potential value of studying the reappearance of normal plasma cells as a surrogate of loss of CAR-T cell functionality and inferior PFS. Dr, Jon P. Oskarsson showed that more than 70% of individuals with MGUS at diagnosis have an abnormal plasma cell population in the bone marrow by multiparameter flow cytometry. A majority of cases in which an abnormal plasma cell population was not detected were found to have either a transient M-protein or a normal FLC ratio in repeated measures during follow-up. These findings suggest that MFC may identify individuals with clinically insignificant MGUS or individuals with a false positive MGUS diagnosis. Further studies with longer follow-up are needed to confirm this important data.
Dr. Noemi Puig discussed the role of mass spectrometry in the response definition of myeloma patients. She presented data where both immunofixation and mass spectrometry were applied in serum samples from newly diagnosed MM patients for the detection of M-protein. Overall, the results of mass spectrometry and immunofixation were concordant in >80% of cases. Compared with immunofixation, mass spectrometry seems to be more sensitive to detect the M-protein of myeloma patients, both at diagnosis and during treatment, and provides a more accurate prediction of patients’ outcomes. The confirmation of this data in large prospective trials will show the future role of mass spectrometry in the follow-up of myeloma patients.
Finally, Dr. Bruno Paiva presented data on the association of comprehensive immune profiling with progression-free survival (PFS) and overall survival (OS). He showed that higher pre-ASCT CD19+ B-cell counts correlated with improved 2-year PFS and OS; this effect was seen primarily in patients with MRD-positive marrow tests. Higher γδ T-cell and CD4+ central memory (CM) cell counts post-ASCT also correlated with improved 2-year OS. The higher γδ T-cell and CD4+ CM-cell count associations were primarily observed in MRD-negative patients post-ASCT and in patients not receiving maintenance therapy. Thus, immune profiling and MRD may be measured in clinical trials of maintenance therapy with novel agents post-ASCT for MM to confirm their utility for prognosis and management.
In an oral presentation, Dr. Romanos Sklavenitis-Pistofidis presented the largest to date study of immune scRNA-seq profiling in patients with smoldering myeloma and the first systematic attempt of this scale to assess the feasibility of using peripheral blood for immune profiling in patients with myeloma. His study demonstrated that peripheral blood mirrors the composition of the bone marrow immune compartment, and provided evidence of post-therapy immune normalization, which could have prognostic implications.