Type: Oral
Session: 652. Multiple Myeloma: Clinical and Epidemiological: Molecular and Biological Signatures and Predictors of Outcomes
Hematology Disease Topics & Pathways:
Research, Translational Research
Methods: We included 170 NDMM patients who were diagnosed between the years of 2010-2015 to ensure sufficient median follow-up time, which was 10 years. Median age of the study cohort was 60 years (range: 34-76), 104 were male (61%), and 31 patients (18%) had high-risk according to gene-expression profiles. All patients underwent PET-CT and DW-MRI evaluation at three pre-defined timepoints: baseline, post autologous stem-cell transplantation (ASCT) and at relapse. Minimal residual disease testing (MRD) by 8 color flow cytometry at a sensitivity level of 10-5 post ASCT was available for 70 patients.
Results: At baseline, 144/170 patients (85%) presented with focal lesions. Both imaging modalities, PET-CT and DW-MRI, showed positive results in 116 patients (68%). However, 21 patients (12%) had focal lesions detectable only by DW-MRI, while 7 patients (4%) showed focal lesions solely in PET-CT. After ASCT, only 12 patients had PET-CT positive lesions, whereas DW-MRI detected focal lesions in 53 patients, indicating a much higher detection rate with DW-MRI. Overall, 55 out of 170 patients (32%) showed residual lesions at this time point. The 26 patients w/o focal lesions in both PET-CT and DW-MRI at baseline remained negative post ASCT. Except for one patient, focal lesions after ASCT were persistent from initial diagnosis. Of note, two-thirds of the patients had residual focal lesions in the humeri and/or femora, which is surprising given that myeloma is considered a disease of the axial skeleton. Next, we correlated the presence of residual lesions with baseline patient characteristics, including age, gender, stage, and cytogenetic risk factors. Compared to patients w/o residual lesions, PET-positive patients showed an enrichment of rISS stage III (7 vs 50%, p<0.001) and deletion 17p (10 vs 33%, p=0.04). In contrast, patients who were DW-MRI positive only showed no significant association with any of the investigated variables. Both PET- and DW-MRI positive lesions post ASCT were associated with poor PFS (median 1.5 and 2.4 years, respectively vs. 9.4 years in imaging-negative patients, p<0.001) and OS (median 3.7 and 5.7 years, respectively vs. 11.3 years, p<0.001). Importantly, in a multivariate model the adverse prognostic effect of residual lesions was independent of baseline risk factors. To increase the power of the following combined imaging/MRD analysis, we defined an “Imaging+” group, which included the patients with PET+ and/or DW-MRI+ focal lesions. Among the 20 patients who achieved MRD-negative and imaging-negative status, an excellent PFS was observed, with only three events occurring in an 8-year follow-up. Residual lesions despite MRD negativity were only seen in two patients, and one of them progressed after 1.5 years. Dismal PFS was seen for double-positive patients (median 1.4 years), significantly worse compared to patients with MRD positivity only (8.9 years).
Conclusion: Taken together, DW-MRI captures more patients with prognostically relevant residual focal lesions compared to PET-CT and should therefore be considered as a preferable imaging modality post ASCT. The high number of residual lesions in the extremities suggests a role of humeri and femora as reservoirs for treatment-resistant cells, deserving further investigation. For patients with MRD and imaging double positivity post ASCT, prognosis is dismal and alternate therapeutic approaches should be considered.
Disclosures: Schinke: Janssen: Consultancy, Honoraria; Pfizer: Honoraria; Arcellx: Consultancy. Rasche: Amgen: Consultancy; BMS: Consultancy, Honoraria, Research Funding; GSK: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Skyline Dx: Research Funding; Sanofi: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Roche: Honoraria. van Rhee: Janssen Pharmaceuticals: Research Funding; GlaxoSmithKline: Consultancy; Bristol Myers Squibb: Research Funding; EUSA Bio: Consultancy; Adicet Bio: Consultancy.
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