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The N,C-coupled naphthylisoquinoline alkaloid ancistrocladinium A belongs to a novel class of natural products with potent antiprotozoal activity. Its effects on tumor cells, however, have not yet been explored. We demonstrate the antitumor activity of ancistrocladinium A in multiple myeloma (MM), a yet incurable blood cancer that represents a model disease for adaptation to proteotoxic stress. Viability assays showed a potent apoptosis-inducing effect of ancistrocladinium A in MM cell lines, including those with proteasome inhibitor (PI) resistance, and in primary MM cells, but not in non-malignant blood cells. Concomitant treatment with the PI carfilzomib or the histone deacetylase inhibitor panobinostat strongly enhanced the ancistrocladinium A-induced apoptosis. Mass spectrometry with biotinylated ancistrocladinium A revealed significant enrichment of RNA-splicing-associated proteins. Affected RNA-splicing-associated pathways included genes involved in proteotoxic stress response, such as PSMB5-associated genes and the heat shock proteins HSP90 and HSP70. Furthermore, we found strong induction of ATF4 and the ATM/H2AX pathway, both of which are critically involved in the integrated cellular response following proteotoxic and oxidative stress. Taken together, our data indicate that ancistrocladinium A targets cellular stress regulation in MM and improves the therapeutic response to PIs or overcomes PI resistance, and thus may represent a promising potential therapeutic agent.
Multiple myeloma (MM) frequently induces persisting osteolytic manifestations despite hematologic treatment response. This study aimed to establish a biometrically valid study endpoint for bone remineralization through quantitative and qualitative analyses in sequential CT scans. Twenty patients (seven women, 58 ± 8 years) with newly diagnosed MM received standardized induction therapy comprising the anti-SLAMF7 antibody elotuzumab, carfilzomib, lenalidomide, and dexamethasone (E-KRd). All patients underwent whole-body low-dose CT scans before and after six cycles of E-KRd. Two radiologists independently recorded osteolytic lesion sizes, as well as the presence of cortical destruction, pathologic fractures, rim and trabecular sclerosis. Bland–Altman analyses and Krippendorff’s α were employed to assess inter-reader reliability, which was high for lesion size measurement (standard error 1.2 mm) and all qualitative criteria assessed (α ≥ 0.74). After six cycles of E-KRd induction, osteolytic lesion size decreased by 22% (p < 0.001). While lesion size response did not correlate with the initial lesion size at baseline imaging (Pearson’s r = 0.144), logistic regression analysis revealed that the majority of responding osteolyses exhibited trabecular sclerosis (p < 0.001). The sum of osteolytic lesion sizes on sequential CT scans defines a reliable study endpoint to characterize bone remineralization. Patient level response is strongly associated with the presence of trabecular sclerosis.
A growing body of literature reports on the upregulation of C-X-C motif chemokine receptor 4 (CXCR4) in a variety of cancer entities, rendering this receptor as suitable target for molecular imaging and endoradiotherapy in a theranostic setting. For instance, the CXCR4-targeting positron emission tomography (PET) agent [\(^{68}\)Ga]PentixaFor has been proven useful for a comprehensive assessment of the current status quo of solid tumors, including adrenocortical carcinoma or small-cell lung cancer. In addition, [\(^{68}\)Ga]PentixaFor has also provided an excellent readout for hematological malignancies, such as multiple myeloma, marginal zone lymphoma, or mantle cell lymphoma. PET-based quantification of the CXCR4 capacities in vivo allows for selecting candidates that would be suitable for treatment using the theranostic equivalent [\(^{177}\)Lu]/[\(^{90}\)Y]PentixaTher. This CXCR4-directed theranostic concept has been used as a conditioning regimen prior to hematopoietic stem cell transplantation and to achieve sufficient anti-lymphoma/-tumor activity in particular for malignant tissues that are highly sensitive to radiation, such as the hematological system. Increasing the safety margin, pretherapeutic dosimetry is routinely performed to determine the optimal activity to enhance therapeutic efficacy and to reduce off-target adverse events. The present review will provide an overview of current applications for CXCR4-directed molecular imaging and will introduce the CXCR4-targeted theranostic concept for advanced hematological malignancies.
Limiting bone resorption and regenerating bone tissue are treatment goals in myeloma bone disease (MMBD). Physical stimuli such as mechanical loading prevent bone destruction and enhance bone mass in the MOPC315.BM.Luc model of MMBD. It is unknown whether treatment with the Bruton's tyrosine kinase inhibitor CC-292 (spebrutinib), which regulates osteoclast differentiation and function, augments the anabolic effect of mechanical loading. CC-292 was administered alone and in combination with axial compressive tibial loading in the MOPC315.BM.Luc model for three weeks. However, neither CC-292 alone nor its use in combination with mechanical loading was more effective in reducing osteolytic bone disease or rescuing bone mass than mechanical stimuli alone, as evidenced by microcomputed tomography (microCT) and histomorphometric analysis. Further studies are needed to investigate novel anti-myeloma and anti-resorptive strategies in combination with physical stimuli to improve treatment of MMBD.
Due to the low frequency of abnormalities affecting the spleen, this organ is often overlooked during radiological examinations. Here, we report on the unexpected finding, that the spleen signal on diffusion-weighted MRI (DW-MRI) is associated with clinical parameters in patients with plasma cell dyscrasias. Methods: We investigated the spleen signal on DW-MRI together with clinical and molecular parameters in 295 transplant-eligible newly diagnosed Multiple Myeloma (NDMM) patients and in 72 cases with monoclonal gammopathy of undetermined significance (MGUS). Results: Usually, the spleen is the abdominal organ with the highest intensities on DW-MRI. Yet, significant signal loss on DW-MRI images was seen in 71 of 295 (24%) NDMM patients. This phenomenon was associated with the level of bone marrow plasmacytosis (P=1x10(-10)) and International Staging System 3 (P=0.0001) but not with gain(1q), and del(17p) or plasma cell gene signatures. The signal was preserved in 72 individuals with monoclonal gammopathy of undetermined significance and generally re-appeared in MM patients responding to treatment, suggesting that lack of signal reflects increased tumor burden. While absence of spleen signal in MM patients with high risk disease defined a subgroup with very poor outcome, re-appearance of the spleen signal after autologous stem cell transplantation was seen in patients with improved outcome. Our preliminary observation suggests that extramedullary hematopoiesis in the spleen is a factor that modifies the DW-MRI signal of this organ. Conclusions: The DW-MRI spleen signal is a promising marker for tumor load and provides prognostic information in MM.
Growing evidence points to multiple myeloma (MM) and its stromal microenvironment using several mechanisms to subvert effective immune and anti-tumor responses. Recent advances have uncovered the tumor-stromal cell influence in regulating the immune-microenvironment and have envisioned targeting these suppressive pathways to improve therapeutic outcomes. Nevertheless, some subgroups of patients include those with particularly unfavorable prognoses. Biological stratification can be used to categorize patient-, disease- or therapy-related factors, or alternatively, these biological determinants can be included in a dynamic model that customizes a given treatment to a specific patient. Genetic heterogeneity and current knowledge enforce a systematic and comprehensive bench-to-bedside approach. Given the increasing role of cancer stem cells (CSCs) in better characterizing the pathogenesis of solid and hematological malignancies, disease relapse, and drug resistance, identifying and describing CSCs is of paramount importance in the management of MM. Even though the function of CSCs is well-known in other cancer types, their role in MM remains elusive. With this review, we aim to provide an update on MM homing and resilience in the bone marrow micro milieu. These data are particularly interesting for clinicians facing unmet medical needs while designing novel treatment approaches for MM.
Background
Multiple myeloma (MM) is the third most common hematologic malignancy with increasing importance due to improving treatment strategies and long-term outcomes in an aging population. This study aims to analyse influencing factors on health-related quality of life (HRQoL), such as treatment strategies, participation in a clinical trial and patient characteristics like anxiety, depression, gender, and age. A better understanding of the individual factors in context with HRQoL could provide a helpful instrument for clinical decisions.
Methods
In this prospective observational study, the HRQoL of MM patients with different therapies (first-line and relapse) was quantified by standardized questionnaires (EORTC QLQ-C30 and -MY20) in the context of sociodemographic data, individual anxiety and depressiveness (PHQ-4), and a selected number of clinical parameters and symptoms at defined time-points before, during, and after therapy.
Results
In total, 70 patients were included in the study. The median age of the study cohort was 62 years. 44% were female and 56% were male patients. More than half of the patients were fully active with an ECOG 0. Global health status was significantly higher in patients with first-line treatment and even increased after start of therapy, while the pain level decreased. In contrast, patients with relapsed MM reported a decreasing global health status and increasing pain. Additionally, there was a higher global health status in less anxious/depressive patients. HRQoL decreased significantly after start of chemotherapy in the parameters body image, side effects of treatment, and cognitive functioning. Tandem stem-cell transplantation was not found to be a risk factor for higher impairment of HRQoL. Participation in a clinical study led to an improvement of most aspects of HRQoL. Among others, increased anxiety and depression, female gender, older age, impaired performance status, and recurrent disease can be early indicators for a reduced HRQoL.
Conclusion
This study showed the importance of regular longitudinal assessments of patient reported outcomes (PROs) in routine clinical care. For the first time, to our knowledge, we were able to demonstrate a potential impact between participation in clinical trials and HRQoL. However, due to frequently restrictive inclusion criteria for clinical trials, these MM patients might not be directly comparable with patients treated within standard therapy concepts. Further studies are needed to clarify the relevance of this preliminary data in order to develop an individualized, patient-centred, therapy concept.
Myeloma is characterized by extensive inter-patient genomic heterogeneity due to multiple different initiating events. A recent multi-region sequencing study demonstrated spatial differences, with progression events, such as TP53 mutations, frequently being restricted to focal lesions. In this review article, we describe the clinical impact of these two types of tumor heterogeneity. Target mutations are often dominant at one site but absent at other sites, which poses a significant challenge to personalized therapy in myeloma. The same holds true for high-risk subclones, which can be locally restricted, and as such not detectable at the iliac crest, which is the usual sampling site. Imaging can improve current risk classifiers and monitoring of residual disease, but does not allow for deciphering the molecular characteristics of tumor clones. In the era of novel immunotherapies, the clinical impact of heterogeneity certainly needs to be re-defined. Yet, preliminary observations indicate an ongoing impact of spatial heterogeneity on the efficacy of monoclonal antibodies. In conclusion, we recommend combining molecular tests with imaging to improve risk prediction and monitoring of residual disease. Overcoming intra-tumor heterogeneity is the prerequisite for curing myeloma. Novel immunotherapies are promising but research addressing their impact on the spatial clonal architecture is highly warranted.
Crizotinib was a first generation of ALK tyrosine kinase inhibitor approved for the treatment of ALK-positive non-small-cell lung carcinoma (NSCLC) patients. COMPARE and cluster analyses of transcriptomic data of the NCI cell line panel indicated that genes with different cellular functions regulated the sensitivity or resistance of cancer cells to crizotinib. Transcription factor binding motif analyses in gene promoters divulged two transcription factors possibly regulating the expression of these genes, i.e., RXRA and GATA1, which are important for leukemia and erythroid development, respectively. COMPARE analyses also implied that cell lines of various cancer types displayed varying degrees of sensitivity to crizotinib. Unexpectedly, leukemia but not lung cancer cells were the most sensitive cells among the different types of NCI cancer cell lines. Re-examining this result in another panel of cell lines indeed revealed that crizotinib exhibited potent cytotoxicity towards acute myeloid leukemia and multiple myeloma cells. P-glycoprotein-overexpressing CEM/ADR5000 leukemia cells were cross-resistant to crizotinib. NCI-H929 multiple myeloma cells were the most sensitive cells. Hence, we evaluated the mode of action of crizotinib on these cells. Although crizotinib is a TKI, it showed highest correlation rates with DNA topoisomerase II inhibitors and tubulin inhibitors. The altered gene expression profiles after crizotinib treatment predicted several networks, where TOP2A and genes related to cell cycle were downregulated. Cell cycle analyses showed that cells incubated with crizotinib for 24 h accumulated in the G\(_2\)M phase. Crizotinib also increased the number of p-H3(Ser10)-positive NCI-H929 cells illustrating crizotinib's ability to prevent mitotic exit. However, cells accumulated in the sub-G\(_0\)G\(_1\) fraction with longer incubation periods, indicating apoptosis induction. Additionally, crizotinib disassembled the tubulin network of U2OS cells expressing an α-tubulin-GFP fusion protein, preventing migration of cancer cells. This result was verified by in vitro tubulin polymerization assays. In silico molecular docking also revealed a strong binding affinity of crizotinib to the colchicine and Vinca alkaloid binding sites. Taken together, these results demonstrate that crizotinib destabilized microtubules. Additionally, the decatenation assay showed that crizotinib partwise inhibited the catalytic activity of DNA topoisomerase II. In conclusion, crizotinib exerted kinase-independent cytotoxic effects through the dual inhibition of tubulin polymerization and topoisomerase II and might be used to treat not only NSCLC but also multiple myeloma.
Clinical and biological characteristics of medullary and extramedullary plasma cell dyscrasias
(2021)
Background: Extramedullary plasma cell (PC) disorders may occur as extramedullary disease in multiple myeloma (MM-EMD) or as primary extramedullary plasmocytoma (pEMP)/solitary osseous plasmocytoma (SOP). In this study, we aimed to obtain insights into the molecular mechanisms of extramedullary spread of clonal PC. Methods: Clinical and biological characteristics of 87 patients with MM-EMD (n = 49), pEMP/SOP (n = 20) and classical MM (n = 18) were analyzed by using immunohistochemistry (CXCR4, CD31, CD44 and CD81 staining) and cytoplasmic immunoglobulin staining combined with fluorescence in situ hybridization (cIg-FISH). Results: High expression of CD44, a cell-surface glycoprotein involved in cell-cell interactions, was significantly enriched in MM-EMD (90%) vs. pEMP/SOP (27%) or classical MM (33%) (p < 0.001). In addition, 1q21 amplification by clonal PC occurred at a similar frequency of MM-EMD (33%), pEMP/SOP (57%) and classical MM (44%). Conversely, del(17p13), t(4;14) and t(14;16) were completely absent in pEMP/SOP. Besides this, 1q21 amplification was identified in 64% of not paraskeletal samples from MM-EMD or pEMP compared to 9% of SOP or paraskeletal MM-EMD/pEMP and 44% of classical MM samples, respectively (p = 0.02). Conclusion: Expression of molecules involved in homing and cytogenetic aberrations differ between MM with or without EMD and pEMP/SOP.
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.
Background: Preservation of kidney function in newly diagnosed (ND) multiple myeloma (MM) helps to prevent excess toxicity. Patients (pts) from two prospective trials were analyzed, provided postinduction (PInd) restaging was performed. Pts received three cycles with bortezomib (btz), cyclophosphamide, and dexamethasone (dex; VCD) or btz, lenalidomide (len), and dex (VRd) or len, adriamycin, and dex (RAD). The minimum required estimated glomerular filtration rate (eGFR) was >30 mL/min. We analyzed the percent change of the renal function using the International Myeloma Working Group (IMWG) criteria and Kidney Disease: Improving Global Outcomes (KDIGO)-defined categories. Results: Seven hundred and seventy-two patients were eligible. Three hundred and fifty-six received VCD, 214 VRd, and 202 RAD. VCD patients had the best baseline eGFR. The proportion of pts with eGFR <45 mL/min decreased from 7.3% at baseline to 1.9% PInd (p < 0.0001). Thirty-seven point one percent of VCD versus 49% of VRd patients had a decrease of GFR (p = 0.0872). IMWG-defined “renal complete response (CRrenal)” was achieved in 17/25 (68%) pts after VCD, 12/19 (63%) after RAD, and 14/27 (52%) after VRd (p = 0.4747). Conclusions: Analyzing a large and representative newly diagnosed myeloma (NDMM) group, we found no difference in CRrenal that occurred independently from the myeloma response across the three regimens. A trend towards deterioration of the renal function with VRd versus VCD may be explained by a better pretreatment “renal fitness” in the latter group.
Published experience with carfilzomib in patients with relapsed/refractory multiple myeloma (RRMM) and extramedullary disease (EMD) is still limited. The current study aimed to assess the efficacy and safety of carfilzomib containing therapy regimens in EMD. We retrospectively analyzed 45 patients with extramedullary RRMM treated with carfilzomib from June 2013 to September 2019. The median age at the start of carfilzomib was 64 (range 40–80) years. Twenty (44%) and 25 (56%) patients had paraosseous manifestation and EMD without adjacency to bone, respectively. The serological overall response rate (ORR) was 59%. Extramedullary response was evaluable in 33 patients, nine (27%) of them achieved partial remission (PR) (ORR = 27%). In 15 (33%) patients, we observed no extramedullary response despite serological response. The median progression-free survival (PFS) and overall survival (OS) were five (95% CI, 3.5–6.5) and ten (95% CI, 7.5–12.5) months, respectively. EMD without adjacency to bone was associated with a significantly inferior PFS (p = 0.004) and OS (p = 0.04) compared to paraosseous lesions. Carfilzomib based treatment strategies showed some efficacy in heavily pretreated patients with extramedullary RRMM but could not overcome the negative prognostic value of EMD. Due to the discrepancy between serological and extramedullary response, evaluation of extramedullary response using imaging is mandatory in these patients.
\(^{11}\)C-methionine (\(^{11}\)C-MET) is a new positron emission tomography (PET) tracer for the assessment of disease activity in multiple myeloma (MM) patients, with preliminary data suggesting higher sensitivity and specificity than \(^{18}\)F-fluorodeoxyglucose (\(^{18}\)F-FDG). However, the value of tumor burden biomarkers has yet to be investigated. Our goals were to corroborate the superiority of \(^{11}\)C-MET for MM staging and to compare its suitability for the assessment of metabolic tumor burden biomarkers in comparison to \(^{18}\)F-FDG. Twenty-two patients with newly diagnosed, treatment-naïve symptomatic MM who had undergone \(^{11}\)C-MET and \(^{18}\)F-FDG PET/CT were evaluated. Standardized uptake values (SUV) were determined and compared with total metabolic tumor volume (TMTV) for both tracers: total lesion glycolysis (TLG) and total lesion \(^{11}\)C-MET uptake (TLMU). PET-derived values were compared to Revised International Staging System (R-ISS), cytogenetic, and serologic MM markers such as M component, beta 2 microglobulin (B2M), serum free light chains (FLC), albumin, and lactate dehydrogenase (LDH). In 11 patients (50%), \(^{11}\)C-MET detected more focal lesions (FL) than FDG (p < 0.01). SUVmax, SUVmean, SUVpeak, TMTV, and TLMU were also significantly higher in \(^{11}\)C-MET than in \(^{18}\)F-FDG (p < 0.05, respectively). \(^{11}\)C-MET PET biomarkers had a better correlation with tumor burden (bone marrow plasma cell infiltration, M component; p < 0.05 versus p = n.s. respectively). This pilot study suggests that \(^{11}\)C-MET PET/CT is a more sensitive marker for the assessment of myeloma tumor burden than \(^{18}\)F-FDG. Its implications for prognosis evaluation need further investigation.
Epidermal growth factor receptor (EGFR) and its ligand heparin-binding EGF-like growth factor (HB-EGF) sustain endothelial cell proliferation and angiogenesis in solid tumors, but little is known about the role of HB-EGF–EGFR signaling in bone marrow angiogenesis and multiple myeloma (MM) progression. We found that bone marrow endothelial cells from patients with MM express high levels of EGFR and HB-EGF, compared with cells from patients with monoclonal gammopathy of undetermined significance, and that overexpressed HB-EGF stimulates EGFR expression in an autocrine loop. We also found that levels of EGFR and HB-EGF parallel MM plasma cell number, and that HB-EGF is a potent inducer of angiogenesis in vitro and in vivo. Moreover, blockade of HB-EGF–EGFR signaling, by an anti-HB-EGF neutralizing antibody or the EGFR inhibitor erlotinib, limited the angiogenic potential of bone marrow endothelial cells and hampered tumor growth in an MM xenograft mouse model. These results identify HB-EGF–EGFR signaling as a potential target of anti-angiogenic therapy, and encourage the clinical investigation of EGFR inhibitors in combination with conventional cytotoxic drugs as a new therapeutic strategy for MM.
Lenalidomide is an integral, yet evolving, part of current treatment pathways for both transplant-eligible and transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). It is approved in combination with dexamethasone as first-line therapy for transplant-ineligible patients with NDMM, and as maintenance treatment following autologous stem cell transplantation (ASCT). Although strong clinical trial evidence has supported the integration of lenalidomide into current treatment paradigms for NDMM, applying those paradigms to individual patients and determining which patients are most likely to benefit from lenalidomide treatment are more complex. In this paper, we utilize the available clinical trial evidence to provide recommendations for patient selection and lenalidomide dosing in both the first-line setting in patients ineligible for ASCT and the maintenance setting in patients who have undergone ASCT. In addition, we provide guidance on management of those adverse events that are most commonly associated with lenalidomide treatment, and consider the optimal selection and sequencing of next-line agents following long-term frontline or maintenance treatment with lenalidomide.
Background
The anti-SLAMF7 monoclonal antibody, elotuzumab (elo), plus lenalidomide (len) and dexamethasone (dex) is approved for relapsed/refractory MM in the U.S. and Europe. Recently, a small phase 2 study demonstrated an advantage in progression-free survival (PFS) for elo plus pomalidomide (pom)/dex compared to pom/dex alone and resulted in licensing of this novel triplet combination, but clinical experience is still limited.
Purpose
To analyze the efficacy and safety of elo/pom/dex in a “real world” cohort of patients with advanced MM, we queried the databases of the university hospitals of Würzburg and Vienna.
Findings
We identified 22 patients with a median number of five prior lines of therapy who received elo/pom/dex prior to licensing within an early access program. Patients received a median number of 5 four-week treatment cycles. Median PFS was 6.4 months with 12-month and 18-month PFS rates of 35% and 28%, respectively. The overall response rate was 50% and 64% of responding patients who achieved a longer PFS with elo/pom/dex compared to their most recent line of therapy. Objective responses were also seen in five patients who had been pretreated with pomalidomide. Low tumor burden was associated with improved PFS (13.5 months for patients with ISS stage I/II at study entry v 6.4 months for ISS III), although this difference did not reach statistical significance. No infusion-related reactions were reported. The most frequent grade 3/4 adverse events were neutropenia and pneumonia.
Conclusion
Elo/pom/dex is an active and well-tolerated regimen in highly advanced MM even after pretreatment with pomalidomide.
We report on a currently 76-year-old female patient with relapsed/refractory (RR) multiple myeloma (MM) treated at our institution. This patient had received six lines of therapy including tandem autologous stem cell transplant, proteasome inhibitor, immunomodulatory drugs and CD38 antibody MOR202. At the last relapse, she progressed during treatment with pomalidomide and MOR202. In an individualized therapy concept, we started a multi-agent salvage therapy with pomalidomide, bortezomib, doxorubicin, dexamethasone, and CD38 antibody daratumumab (“Pom-PAD-Dara”), which resulted in a stringent complete remission with minimal residual disease (MRD) negativity after nine cycles. So far, our patient shows a progression free survival of more than 12 months. Our case demonstrates the feasibility of successful CD38 antibody retreatment in a patient with heavily pretreated CD38 antibody resistant MM.
Utilizing 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT), we performed this pilot study to evaluate the link between cytogenetic/genomic markers and imaging patterns in relapsed/refractory (RR) multiple myeloma (MM). We retrospectively analyzed data of 24 patients with RRMM who were treated at our institution between November 2018 and February 2020. At the last relapse/progression, patients had been treated with a median of three (range 1–10) lines of therapy. Six (25%) patients showed FDG avid extramedullary disease without adjacency to bone. We observed significantly higher maximum standardized uptake values (SUV\(_{max}\)) in patients harboring del(17p) compared with those without del(17p) (p = 0.025). Moreover, a high SUV\(_{max}\) of >15 indicated significantly shortened progression-free survival (PFS) (p = 0.01) and overall survival (OS) (p = 0.0002). One female patient exhibited biallelic TP53 alteration, i.e., deletion and mutation, in whom an extremely high SUV\(_{max}\) of 37.88 was observed. In summary, this pilot study suggested a link between del(17p)/TP53 alteration and high SUV\(_{max}\) on 18F-FDG PET/CT in RRMM patients. Further investigations are highly warranted at this point.