Brian Østergaard

Smoldering multiple myeloma risk factors for progression: a Danish population‐based cohort study

Several risk scores for disease progression in patients with smoldering multiple myeloma (SMM) have been proposed; however, all have been developed using single‐center registries. To examine risk factors for time to progression (TTP) to multiple myeloma (MM) for SMM, we analyzed a nationwide population‐based cohort of 321 patients with newly diagnosed SMM registered within the Danish Multiple Myeloma Registry between 2005 and 2014. Significant univariable risk factors for TTP were selected for multivariable Cox regression analyses. We found that both an M‐protein ≥30 g/L and immunoparesis significantly influenced TTP (HR 2.7, 95%CI (1.5;4.7), P = 0.001, and HR 3.3, 95%CI (1.4;7.8), P = 0.002, respectively). High free light chain (FLC) ratio did not significantly influence TTP in our cohort. Therefore, our data do not support recent IMWG proposal of identifying patients with FLC ratio above 100 as having ultra high‐risk of transformation to MM. Using only immunoparesis and M‐protein ≥30 g/L, we created a scoring system to identify low‐, intermediate‐, and high‐risk SMM. This first population‐based study of patients with SMM confirms that an M‐protein ≥30 g/L and immunoparesis remain important risk factors for progression to MM.

Proteasome inhibitors and IMiDs can overcome some high-risk cytogenetics in multiple myeloma but not gain 1q21.

Chromosomal aberrations have significant prognostic importance in multiple myeloma (MM). However, proteasome inhibitors (PI) and IMiDs may partly overcome the poor prognostic impact of some of them. In this study, we investigated a population‐based consecutive cohort newly diagnosed patients with MM admitted during a defined time period to hospitals in Denmark, Norway, and Sweden. The impact of treatment modality on the prognostic importance of specific chromosomal aberration was investigated, with special reference to gain 1q21. The median follow‐up of patients still alive at analysis was 40 months for the high‐dose (HDT)‐treated ones and 29 months for the whole population. Three hundred forty‐seven patients with a known 1q21 status were included in this study. The 347 patients were divided into three groups, that is, 119 patients with the 1q21 gain, 105 patients with other aberrations (OA), that is, del(13q), del(17p), t(4,14), and/or (14;16), and 123 patients with no aberrations (NA). The groups were compared in terms of overall survival (OS), time to progression (TTP), and response. The 3‐yr OS for patients with gain 1q21 was 60% compared to patients with OA 74% and NO 82% (gain 1q21 vs. NO P < 0.001; gain 1q21 vs. OA P = 0.095). If treated with PI or IMiDs, the 3‐yr OS was 58% for patients with gain 1q21 compared to patients with OA 78% and NO 78%, respectively (P = 0.041, P = 0.140). In HDT patients, the 3‐yr OS was 69% for patients with gain 1q21 compared to patients with OA 84% and NO 88%, respectively (P < 0.008, P = 0.600). Thus, neither HDT nor using PI or IMiDs could overcome the poor prognostic impact of gain 1q21, while these drugs and HDT seemed to improve OS in patients with OA, approaching the survival in NO. Further, gain 1q21 appears to be one of the most important poor prognostic chromosomal aberrations in multiple myeloma with current treatments. Trials using new drugs or allogeneic transplantation are warranted.

Myc protein overexpression is a feature of progression and adverse prognosis in multiple myeloma

Prognostic and predictive markers in multiple myeloma are continuously explored because of the heterogeneity of the tumor biology. Myc protein is the final product from activating MYC oncogene, but the prognostic impact in multiple myeloma is not well described.

FDG PET/CT in multiple myeloma: changed FDG uptake in the brain of patients receiving high dose chemotherapy

European Journal of Nuclear Medicine and Molecular Imaging Volume 44, Supplement 2 10.1007/s00259-017-3822-1 This supplement was not sponsored by outside commercial interests. It was funded entirely by the association’s own resources DOI 10.1007/s00259-017-3822-1 S119 Eur J Nucl Med Mol Imaging (2017) 44 (Suppl 2):S119–S956

FDG-PET/CT in multiple myeloma: dual time point imaging results can predict response to treatment in patients recieving high dose chemotherapy

European Journal of Nuclear Medicine and Molecular Imaging Volume 44, Supplement 2 10.1007/s00259-017-3822-1 This supplement was not sponsored by outside commercial interests. It was funded entirely by the association’s own resources DOI 10.1007/s00259-017-3822-1 S119 Eur J Nucl Med Mol Imaging (2017) 44 (Suppl 2):S119–S956

NaF-PET/CT in multiple myeloma: assessing bone remodeling at baseline in newly diagnosed myeloma patients compared to a healthy control group

European Journal of Nuclear Medicine and Molecular Imaging Volume 44, Supplement 2 10.1007/s00259-017-3822-1 This supplement was not sponsored by outside commercial interests. It was funded entirely by the association’s own resources DOI 10.1007/s00259-017-3822-1 S119 Eur J Nucl Med Mol Imaging (2017) 44 (Suppl 2):S119–S956

FDG-PET/CT in multiple myeloma: Correlation between SUV and standard prognostic scoring system in multiple myeloma

Hypothesis: We assessed in in vitro and in vivo models of ovarian cancer the therapeutic efficacy of 16F12 mAbs directed against Mullerian Inhibiting Substance type II receptor (MISRII) radiolabeled with 213Bi Methods: In vitro, both direct and bystander cytotoxic effects were measured using clonogenic assay and standard medium transfer protocol. Typically, Clonogenic survival was assessed in SK-OV-3 donor cells expressing MISRII and exposed for 90 min to 0.06-0.5MBq/mL of 16F12 213Bi-mAbs. Bystander cytotoxicity was measured in recipient cells grown in non-radioactive culture medium preconditioned for 2 hours in the presence of donor cells. DNA double strand breaks (DSBs) were measured in both donor and recipients cells using immunofluorescent detection of gamma-H2AX and of 53BP1. In vivo we explored in athymic nude mice bearing intraperitoneal (IP) MISRII-expressing AN3CA tumor the therapeutic efficacy of brief-intraperitoneal radioimmunotherapy (BIP-RIT, 12.95 37 MBq; 37MBq/mg) or of intraperitoneal RIT (IP-RIT; 2.96-12.95 MBq; 37MBq/mg) using 213Bi-16F12. BIP-RIT mimics hyperthermic intraperitoneal chemotherapy as used in clinic. It consists of intraperitoneal injection of high activities of radiolabeled mAbs followed 30 min later by wash of the peritoneal cavity with saline solution to remove unbound radioactivity. The biodistribution of radiolabeled antibodies following IP-RIT (12.95 MBq; 37MBq/mg) or BIP-RIT (37 MBq; 37MBq/mg) was assessed. Results: In vitro we showed in donor cells a strong direct cytotoxicity of 16F12 213Bi-mAbs. A significant bystander cytotoxicity was also measured in recipient cells. Genotoxic effects were also demonstrated as measured by the formation of DNA DSBs in both donor and recipient cells. In vivo, results of biodistribution indicated that tumour uptake of 213Bi-16F12 during BIP RIT was higher than after IP RIT. The tumour-to-blood uptake ratio was 9 versus 3, respectively, one hour post RIT while it decreased down to 3 and 1, respectively, three hours post-RIT. Finally, a similar delay in tumor growth was observed in mice treated with 12.95 MBq of 213Bi-16F12 following IP-RIT or treated with 37 MBq using BIP-RIT. Conclusions: We confirmed in vitro the therapeutic efficacy of newly developed 16F12 213Bi-mAbs. in vivo results indicate that similar therapeutic efficacy and lower toxicity could be obtained with BIP-RIT compared with IP-RIT. BIP-RIT could be a new tool in the therapy of peritoneal carcinomatosis. URI: Authors: LADJOHOUNLOU Riad PICHARD Alexandre DEHAYES E BOUDOUSQ Vincent BRUCHERTSEIFER Frank MORGENSTERN Alfred NAVARRO-TEULON Isabelle POUGET Jean-Pierre Publication Year: 2016 Science Areas: Health and consumer protection [1]European Journal of Nuclear Medicine and Molecular Imaging Volume 43, Supplement 1 10.1007/s00259-016-3484-4 This supplement was not sponsored by outside commercial interests. It was funded entirely by the association’s own resources. ABSTRACT DOI 10.1007/s00259-016-3484-4 Eur J Nucl Med Mol Imaging (2016) 43 (Suppl 1):S1–S734Background: In the context of the EORTC LungTech trial, a QA procedure including a PET/CT credentialing has been developed. This procedure will ultimately allow us to pool data from 23 institutions with the overall goal of investigating the impact of tumour motion on quantification. As no standardized procedure exists under respiratory conditions, we investigated the variability of 14 SUV metrics to assess their robustness over respiratory noise. Methods: The customized CIRS-008A phantom was scanned at 13 institutions. This phantom consists of a 18 cm long body, a rod attached to a motion actuator, and a sphere of either 1.5 or 2.5cm diameters. Body, rods and spheres were filled with homogeneous 18FDG solutions representative of activity concentrations in mediastinum, lung and tumour for a 70kg patient. Three respiratory patterns with peak-to-peak amplitudes and periods of 15mm/3sec, 15mm/6sec and 25mm/4sec were tested. Prior to scanning in respiratory condition, a 3D static PET/CT was acquired as reference. During motion, images were acquired using 3D or 4D gated PET(average image) according to institutional settings. 14 SUV(mean) metrics were obtained per acquisition varying VOI/ ROI shape and location. Three ROIs and three VOIs with respective radii of 0.5, 0.6 and 0.8cm were investigated. These ROIs/VOIs were first centred on the maximum activity voxel; a second analysis was made changing the location from the voxel to the region (ROI5voxels) or the volume (VOI7voxels) with the maximum value. Two additional VOIs were defined as 3D isocontours respectively at 70% and 50% of the maximum voxel value. The SUV metrics were normalized by the corresponding 3D static SUV. Converting to recovery coefficients (RC) allowed us to pool data from all institutions, while maintaining focus solely on motion. For each RC from each motion setting we calculated the mean over institutions, we then looked at the standard deviation (Sd) and spread of each averaged RC over each motion setting (formula [1], [2], Figure1). Results: For the institutions visited we found that RCVOI70% and RCVOI50%, yielded over the 14 metrics the lowest variability to motion with Sd of 0.04 and 0.03 respectively. The RCs based on ROIs/VOIs centered on a single voxel were less impacted by motion (Sd: 0.08) compared to region RCs (Sd: 0.14). The averaged Sd over the RCs based on VOIs and ROIs was 0.12 and 0.11 respectively. Conclusion: Quantification over breathing types depends on ROI/VOI definition. Variables based on SUV max thresholds were found the most robust against respiratory noise.