Search

The multi‐agent therapy "VDT‐PACE" represents an established regimen in relapsed/refractory multiple myeloma (RRMM). Here, we report on our experience with a "modified VDT‐PACE" incorporating new generation anti‐MM agents daratumumab and carfilzomib ("Dara‐KDT‐P(A)CE"). We retrospectively analyzed 38 patients with RRMM treated with "Dara‐KDT‐P(A)CE". The median age was 62 (range 45–82) years, and the patients were heavily pretreated with a median of 5 (range 2–12) prior lines of therapy. Twenty‐one (55%) patients suffered from penta‐refractory MM. High‐risk cytogenetics was present in 31 (81%) patients. The patients received a median of 2 (range 1–10) cycles of this therapy, and the overall response rate (ORR) was 70%. Patients with penta‐refractory MM and high‐risk cytogenetics showed similar ORR of 65% and 79%, respectively. The median progression‐free survival (PFS) and overall survival were 4.1 (95% CI 2.7–5.4) and 8.4 (95% CI 6.7–10.0) months, respectively. Patients with lactate dehydrogenase >250 IU/L showed significantly shorter PFS in comparison with others patients (p = 0.006). We used this regimen as bridging therapy prior to chimeric antigen receptor T‐cell infusion in four patients. In conclusion, "Dara‐KDT‐P(A)CE" is an effective salvage therapy for patients with heavily pretreated, multi‐refractory, high‐risk RRMM lacking alternative options. [ABSTRACT FROM AUTHOR]

Beyond being a key factor for tumor growth and metastasis in human cancer, C-X-C motif chemokine receptor 4 (CXCR4) is also highly expressed by a number of immune cells, allowing for non-invasive read-out of inflammatory activity. With two recent studies reporting on prognostic implications of the spleen signal in diffusion-weighted magnetic resonance imaging in patients with plasma cell dyscrasias, the aim of this study was to correlate splenic 68 Ga-Pentixafor uptake in multiple myeloma (MM) with clinical parameters and to evaluate its prognostic impact. Methods: Eighty-seven MM patients underwent molecular imaging with 68 Ga-Pentixafor-PET/CT. Splenic CXCR4 expression was semi-quantitatively assessed by peak standardized uptake values (SUV peak ) and corresponding spleen-to-bloodpool ratios (TBR) and correlated with clinical and prognostic features as well as survival parameters. Results: 68 Ga-Pentixafor-PET/CT was visually positive in all MM patients with markedly heterogeneous tracer uptake in the spleen. CXCR4 expression determined by 68 Ga-Pentixafor-PET/CT corresponded with advanced disease and was inversely associated with the number of previous treatment lines as compared to controls or untreated smouldering multiple myeloma patients (SUV peak Spleen 4.06 ± 1.43 vs. 6.02 ± 1.16 vs. 7.33 ± 1.40; P < 0.001). Moreover, reduced splenic 68 Ga-Pentixafor uptake was linked to unfavorable clinical outcome. Patients with a low SUV peak Spleen (<3.35) experienced a significantly shorter overall survival of 5 months as compared to 62 months in patients with a high SUV peak Spleen >5.79 ( P < 0.001). Multivariate Cox analysis confirmed SUV peak Spleen as an independent predictor of survival (HR 0.75; P = 0.009). Conclusion: These data suggest that splenic 68 Ga-Pentixafor uptake might provide prognostic information in pre-treated MM patients similar to what was reported for diffusion-weighted magnetic resonance imaging. Further research to elucidate the underlying biologic implications is warranted., Competing Interests: Competing Interests: Hans-Jürgen Wester is the founder and shareholder of Scintomics. Ulrich Keller received advisory board fees from Pentixapharm. All other authors have declared that no competing interest exists., (© The author(s).)

PET with 18 F-FDG is the standard modality in nuclear medicine for imaging multiple myeloma (MM). However, viable MM as detected by MRI or PET with other metabolic tracers, including 11 C-methionine, may be missed-for example, because of low hexokinase 2 (HK2) expression of tumor cells. The aim of this study was to further investigate potential reasons for PET false negativity. Methods: A cohort of 15 mainly pretreated patients with relapsed or refractory biopsy-proven, serologically active MM who underwent both 18 F-FDG and 11 C-methionine PET/CT was retrospectively analyzed. Results: In 9 of the 15 patients, 18 F-FDG PET was negative in the presence of viable disease. In the remaining 6 patients, both 18 F-FDG and 11 C-methionine PET/CT revealed the same number of MM lesions. At immunohistochemistry, 18 F-FDG-negative myeloma did not exhibit significant differences in HK2 or glucose-6-phosphatase expression from 18 F-FDG-positive disease ( P = 0.57 and P = 0.44, respectively). Conclusion: Beyond HK2 expression, 18 F-FDG negativity in (mainly pretreated) MM patients seems to be associated with additional causes not yet known., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

Over the past 10 years next generation sequencing (NGS) approaches deciphered a large number of genomes from a wide variety of tumor types. However, despite most relevant findings, this technology has not yet been implemented into standard diagnostic workflows. Broad access to NGS technology is still limited, sequencing/analysis times exceed clinically relevant timeframes and despite huge cuts, costs remain significant. We proposed a custom-tailored gene panel, which focuses on a selected number of relevant genes and developed a clinically oriented NGS targeted sequencing approach for the molecular characterization of Multiple Myeloma (MM) tumors, allowing the description of the tumor genetic heterogeneity and its changes under selective pressure of antitumor therapy, in a more cost effective and faster turnaround timeframe.

11 C-methionine (MET) has recently emerged as an accurate marker of tumor burden and disease activity in patients with multiple myeloma (MM). This dual-center study aimed at further corroboration of the superiority of MET as positron emission tomography (PET) tracer for staging and re-staging MM, as compared to 18 F-2`-deoxy-2`-fluoro-D-glucose (FDG). 78 patients with a history of solitary plasmacytoma (n=4), smoldering MM (SMM, n=5), and symptomatic MM (n=69) underwent both MET- and FDG-PET/computed tomography (CT) at the University Centers of Würzburg, Germany and Navarra, Spain. Scans were compared on a patient and on a lesion basis. Inter-reader agreement was also evaluated. In 2 patients, tumor biopsies for verification of discordant imaging results were available. MET-PET detected focal lesions (FL) in 59/78 subjects (75.6%), whereas FDG-PET/CT showed lesions in only 47 patients (60.3%; p<0.01), accordingly disease activity would have been missed in 12 patients. Directed biopsies of discordant results confirmed MET-PET/CT results in both cases. MET depicted more FL in 44 patients (56.4%; p<0.01), whereas in two patients (2/78), FDG proved superior. In the remainder (41.0%, 32/78), both tracers yielded comparable results. Inter-reader agreement for MET was higher than for FDG (κ = 0.82 vs κ = 0.72). This study demonstrates higher sensitivity of MET in comparison to standard FDG to detect intra- and extramedullary MM including histologic evidence of FDG-negative, viable disease exclusively detectable by MET-PET/CT. MET holds the potential to replace FDG as functional imaging standard for staging and re-staging of MM., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Chemokine (C-X-C motif) receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer including multiple myeloma (MM). Proof-of-concept of CXCR4-directed radionuclide therapy in MM has recently been reported. This study assessed the diagnostic performance of the CXCR4-directed radiotracer [ 68 Ga]Pentixafor in MM and a potential role for stratifying patients to CXCR4-directed therapies. Thirty-five patients with MM underwent [ 68 Ga]Pentixafor-PET/CT for evaluation of eligibility for endoradiotherapy. In 19/35 cases, [ 18 F]FDG-PET/CT for correlation was available. Scans were compared on a patient and on a lesion basis. Tracer uptake was correlated with standard clinical parameters of disease activity. [ 68 Ga]Pentixafor-PET detected CXCR4-positive disease in 23/35 subjects (66%). CXCR4-positivity at PET was independent from myeloma subtypes, cytogenetics or any serological parameters and turned out as a negative prognostic factor. In the 19 patients in whom a comparison to [ 18 F]FDG was available, [ 68 Ga]Pentixafor-PET detected more lesions in 4/19 (21%) subjects, [ 18 F]FDG proved superior in 7/19 (37%). In the remaining 8/19 (42%) patients, both tracers detected an equal number of lesions. [ 18 F]FDG-PET positivity correlated with [ 68 Ga]Pentixafor-PET positivity (p=0.018). [ 68 Ga]Pentixafor-PET provides further evidence that CXCR4 expression frequently occurs in advanced multiple myeloma, representing a negative prognostic factor and a potential target for myeloma specific treatment. However, selecting patients for CXCR4 directed therapies and prognostic stratification seem to be more relevant clinical applications for this novel imaging modality, rather than diagnostic imaging of myeloma., Competing Interests: HJW is founder and shareholder of Scintomics. SK is CEO of Scintomics. All other authors declare no conflicts of interest.