Vascular thrombotic events in the era of modern myeloma therapy.

The treatment landscape in multiple myeloma (MM) has changed drastically in the past two decades with new treatment paradigms evolving. In this issue Sborov et al. provide the first study investigating the frequency, severity, onset of vascular thrombotic events (VTEs) and use of prophylactic therapies in a trial applying a contemporary myeloma treatment protocol and highlight that prevention of VTEs needs to be revisited in the era of modern myeloma treatment. Commentary on: Sborov et al. Daratumumab plus lenalidomide, bortezomib and dexamethasone in newly diagnosed multiple myeloma: Analysis of vascular thrombotic events in the GRIFFIN study. Br J Haematol. 2022;199:355-365.

Deep Learning for Automatic Bone Marrow Apparent Diffusion Coefficient Measurements From Whole-Body Magnetic Resonance Imaging in Patients With Multiple Myeloma: A Retrospective Multicenter Study.

OBJECTIVES: Diffusion-weighted magnetic resonance imaging (MRI) is increasingly important in patients with multiple myeloma (MM). The objective of this study was to train and test an algorithm for automatic pelvic bone marrow analysis from whole-body apparent diffusion coefficient (ADC) maps in patients with MM, which automatically segments pelvic bones and subsequently extracts objective, representative ADC measurements from each bone. MATERIALS AND METHODS: In this retrospective multicentric study, 180 MRIs from 54 patients were annotated (semi)manually and used to train an nnU-Net for automatic, individual segmentation of the right hip bone, the left hip bone, and the sacral bone. The quality of the automatic segmentation was evaluated on 15 manually segmented whole-body MRIs from 3 centers using the dice score. In 3 independent test sets from 3 centers, which comprised a total of 312 whole-body MRIs, agreement between automatically extracted mean ADC values from the nnU-Net segmentation and manual ADC measurements from 2 independent radiologists was evaluated. Bland-Altman plots were constructed, and absolute bias, relative bias to mean, limits of agreement, and coefficients of variation were calculated. In 56 patients with newly diagnosed MM who had undergone bone marrow biopsy, ADC measurements were correlated with biopsy results using Spearman correlation. RESULTS: The ADC-nnU-Net achieved automatic segmentations with mean dice scores of 0.92, 0.93, and 0.85 for the right pelvis, the left pelvis, and the sacral bone, whereas the interrater experiment gave mean dice scores of 0.86, 0.86, and 0.77, respectively. The agreement between radiologists' manual ADC measurements and automatic ADC measurements was as follows: the bias between the first reader and the automatic approach was 49 × 10 -6 mm 2 /s, 7 × 10 -6 mm 2 /s, and -58 × 10 -6 mm 2 /s, and the bias between the second reader and the automatic approach was 12 × 10 -6 mm 2 /s, 2 × 10 -6 mm 2 /s, and -66 × 10 -6 mm 2 /s for the right pelvis, the left pelvis, and the sacral bone, respectively. The bias between reader 1 and reader 2 was 40 × 10 -6 mm 2 /s, 8 × 10 -6 mm 2 /s, and 7 × 10 -6 mm 2 /s, and the mean absolute difference between manual readers was 84 × 10 -6 mm 2 /s, 65 × 10 -6 mm 2 /s, and 75 × 10 -6 mm 2 /s. Automatically extracted ADC values significantly correlated with bone marrow plasma cell infiltration ( R = 0.36, P = 0.007). CONCLUSIONS: In this study, a nnU-Net was trained that can automatically segment pelvic bone marrow from whole-body ADC maps in multicentric data sets with a quality comparable to manual segmentations. This approach allows automatic, objective bone marrow ADC measurements, which agree well with manual ADC measurements and can help to overcome interrater variability or nonrepresentative measurements. Automatically extracted ADC values significantly correlate with bone marrow plasma cell infiltration and might be of value for automatic staging, risk stratification, or therapy response assessment.

Analysis of long-term survival in multiple myeloma after first-line autologous stem cell transplantation: impact of clinical risk factors and sustained response.

The widespread use of high-dose therapy and autologous stem cell transplantation (ASCT) as well as the introduction of novel agents have significantly improved outcomes in multiple myeloma (MM) enabling long-term survival. We here analyze factors influencing survival in 865 newly diagnosed MM patients who underwent first-line ASCT at our center between 1993 and 2014. Relative survival and conditional survival were assessed to further characterize long-term survivors. Achievement of complete response (CR) post-ASCT was associated with prolonged progression-free survival (PFS) in the whole cohort and with significantly superior overall survival (OS) in the subgroup of patients receiving novel agent-based induction therapy. Landmark analyses performed at 1, 3, and 5 years post-ASCT revealed that sustainment of any response had a highly significant influence on survival with no significant differences between sustained CR and sustained inferior responses. Furthermore, outcome was independently improved by administration of maintenance therapy. A subset of patients did experience long-term survival >15 years. However, conditional survival demonstrated a persistent risk of myeloma-associated death and cumulative relative survival curves did not show development of a clear plateau, even in prognostically advantageous groups. In conclusion, in this large retrospective study, sustained response after first-line ASCT was found to be a major prognostic factor for OS independent of depth of sustained response. Administration of maintenance therapy further improved outcome, supporting the hypothesis that interventions to prolong responses achieved post-ASCT may be essential to reach long-term survival, especially in the setting of persisting residual disease.