Bone SPECT/CT in the diagnosis and treatment decision making of axial pain Marta Romera, Víctor Rodrigo-Paradells, Nicolás Varela, Edgar F. Guillén, Marta Navarro-Astiasarán, et al. European Spine Journal, 2025 Purpose To explore the usefulness of bone SPECT/CT for providing additional information to Magnetic Resonance Imaging (MRI) in patients with axial pain, and for guiding the site of spinal injections. Methods We studied 194 patients with axial pain evaluated with SPECT/CT and MRI. Imaging abnormalities were classified according to location and diagnosis of pain generators. Patient outcomes after SPECT/CT guided spinal injection were evaluated during clinical follow-up. Descriptive analyses and kappa coefficient were performed for facet joint arthropathy detection and degenerative disc disease between imaging modalities. Results MRI showed 44.3% more abnormalities than SPECT/CT (329 vs. 228). However, SPECT/CT detected 17% more patients with facet joint arthropathy compared to MRI (43.3% vs. 26.3% respectively). Imaging agreement for diagnosing degenerative disc disease was moderate (κ: 0.44; 95% CI, 0.32–0.56), but only fair for facet joint arthropathy (κ: 0.35; 95% CI, 0.28–0.42). The response to spinal injections guided by SPECT/CT imaging was assessed in 56 patients with facet joint arthropathy. Among these, 26 /56 had a history of previous spinal injections guided by physical examination. In this group, the response was effective or partially effective in 65.4% of patients and ineffective in 34.6%. After a second injection guided by SPECT/CT, the response rate increased to 88.4%, with only 11.6% remaining ineffective, resulting in an absolute benefit of 23.4%. In 30/56 patients with no prior history of spinal injections, the therapy was effective or partially effective in 93.3%, while 6.7% did not show any improvement in pain after SPECT/CT-guided spinal injections. Conclusion Bone SPECT/CT imaging complements MRI by providing valuable information to identify pain generators. In facet joint arthropathy, it improves the effectiveness of pain relief when used to guide spinal injections.
Minimally Invasive Assessment of Peripheral Residual Disease during Maintenance or Observation in Transplant-Eligible Patients with Multiple Myeloma Marta Lasa, Laura Notarfranchi, Cristina Agullo, Carmen Gonzalez, Sergio Castro, et al. Journal of Clinical Oncology, 2025 Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. In multiple myeloma (MM), measurable residual disease (MRD) is assessed in bone marrow (BM). However, less invasive evaluation of peripheral residual disease (PRD) in blood could be advantageous and less cumbersome. We investigated the prognostic value of PRD monitoring after 24 cycles of maintenance in 138 transplant-eligible patients with MM enrolled in the GEM2012MENOS65/GEM2014MAIN clinical trials. PRD was assessed using next-generation flow (NGF) and mass spectrometry (MS). Positive PRD by NGF in 16/138 (11.5%) patients was associated with a 13-fold increased risk of progression and/or death; median progression-free survival (PFS) and overall survival (OS) were 2.5 and 47 months, respectively. Considering patients' MRD status in BM as the reference, PRD detection using NGF showed positive and negative predictive values of 100% and 73%, respectively. Presence of PRD helped identifying patients at risk of imminent progression among those with positive MRD in BM. Patients with undetectable PRD according to both NGF and MS showed 2-year PFS and OS rates of 97% and 100%, respectively. In multivariate analyses including the Revised International Staging System and the complete remission status, only MRD in BM and PRD by NGF showed independent prognostic value for PFS. This study supports the use of less invasive PRD monitoring during maintenance or observation in transplant-eligible patients with MM.
Predictors of unsustained measurable residual disease negativity in transplant-eligible patients with multiple myeloma Camila Guerrero, Noemi Puig, María-Teresa Cedena, María-José Calasanz, Norma C. Gutierrez, et al. Blood, 2024 The role of measurable residual disease (MRD) negativity as a biomarker to stop treatment is being investigated in transplant-eligible patients with multiple myeloma (MM). Thus, it is important to identify risk factors of MRD resurgence and/or progressive disease (PD) among patients achieving undetectable MRD to avoid undertreating them. Here, we studied 267 newly diagnosed transplant-eligible patients with MM enrolled in the GEM2012MENOS65 and GEM2014MAIN clinical trials who achieved MRD negativity by next-generation flow cytometry. After a median follow-up of 73 months since the first MRD negative assessment, 111 of the 267 (42%) patients showed MRD resurgence and/or PD. The only prognostic factors at diagnosis that predicted MRD resurgence and/or PD were an International Staging System (ISS) 3 and the presence of ≥0.01% circulating tumor cells (CTCs). Failure to achieve MRD negativity after induction also predicted higher risk of MRD resurgence and/or PD. Patients having 0 vs 1 vs ≥2 risk factors (ISS 3, ≥0.01% CTCs, and late MRD negativity) showed 5-year rates of MRD resurgence and/or PD of 16%, 33%, and 57%, respectively (P < .001). Thus, these easily measurable risk factors could help refine the selection of patients for whom treatment cessation after MRD negativity is being investigated in clinical trials. This trial was registered at www.clinicaltrials.gov as NCT01916252 and NCT02406144.
Immunogenomic identification and characterization of granulocytic myeloid-derived suppressor cells in multiple myeloma Cristina Perez, Cirino Botta, Aintzane Zabaleta, Noemi Puig, Maria-Teresa Cedena, et al. Blood, 2020 Granulocytic myeloid-derived suppressor cells (G-MDSCs) promote tumor growth and immunosuppression in multiple myeloma (MM). However, their phenotype is not well established for accurate monitoring or clinical translation. We aimed to provide the phenotypic profile of G-MDSCs based on their prognostic significance in MM, immunosuppressive potential, and molecular program. The preestablished phenotype of G-MDSCs was evaluated in bone marrow samples from controls and MM patients using multidimensional flow cytometry; surprisingly, we found that CD11b+CD14−CD15+CD33+HLADR− cells overlapped with common eosinophils and neutrophils, which were not expanded in MM patients. Therefore, we relied on automated clustering to unbiasedly identify all granulocytic subsets in the tumor microenvironment: basophils, eosinophils, and immature, intermediate, and mature neutrophils. In a series of 267 newly diagnosed MM patients (GEM2012MENOS65 trial), only the frequency of mature neutrophils at diagnosis was significantly associated with patient outcome, and a high mature neutrophil/T-cell ratio resulted in inferior progression-free survival (P < .001). Upon fluorescence-activated cell sorting of each neutrophil subset, T-cell proliferation decreased in the presence of mature neutrophils (0.5-fold; P = .016), and the cytotoxic potential of T cells engaged by a BCMA×CD3-bispecific antibody increased notably with the depletion of mature neutrophils (fourfold; P = .0007). Most interestingly, RNA sequencing of the 3 subsets revealed that G-MDSC–related genes were specifically upregulated in mature neutrophils from MM patients vs controls because of differential chromatin accessibility. Taken together, our results establish a correlation between the clinical significance, immunosuppressive potential, and transcriptional network of well-defined neutrophil subsets, providing for the first time a set of optimal markers (CD11b/CD13/CD16) for accurate monitoring of G-MDSCs in MM.
