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BIOMARKER:

Chr t(4;14)

17d
Carfilzomib, Pomalidomide, and Dexamethasone in Treating Patients With High-Risk Multiple Myeloma (clinicaltrials.gov)
P2, N=29, Active, not recruiting, Emory University | Trial completion date: Aug 2024 --> Mar 2026 | Trial primary completion date: Jul 2024 --> Mar 2025
Trial completion date • Trial primary completion date
|
Chr t(4;14) • Chr t(14;16)
|
carfilzomib • pomalidomide
29d
SKY92 Molecular Profiling in Combination With MRD Risk Profiling to Identify High-Risk Multiple Myeloma Patients in Ireland (SKIP-MM) (EACR-AACR 2024)
We continue to evaluate the clinical significance of SKY92 in combination with MRD testing as a superior prognostic repertoire of testing. These methods will improve risk stratification, and in future aid with risk-adapted therapy approaches.
Clinical • Combination therapy
|
Chr t(4;14)
|
LymphoTrack® Dx IGH Assay
1m
ECT-001 (UM171) Expanded Cord Blood Transplant to Treat High-risk Multiple Myeloma (clinicaltrials.gov)
P1/2, N=20, Active, not recruiting, Ciusss de L'Est de l'Île de Montréal | Trial primary completion date: Sep 2021 --> Oct 2023
Trial primary completion date
|
CD34 (CD34 molecule)
|
Chr del(17p) • Chr t(4;14) • Chr t(14;16) • Chr t(14;20) • C1As
|
cyclophosphamide • melphalan • ECT-001-CB
2ms
Gene signatures to therapeutics: Assessing the potential of ivermectin against t(4;14) multiple myeloma. (PubMed, World J Clin Oncol)
Collectively, the findings offer valuable molecular insights for biomarker validation and potential drug development in t(4;14) MM diagnosis and treatment, with ivermectin emerging as a potential therapeutic alternative.
Journal • Gene Signature
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CXCL12 (C-X-C Motif Chemokine Ligand 12) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • NCAM1 (Neural cell adhesion molecule 1) • CCL3 (C-C Motif Chemokine Ligand 3) • CCR2 (C-C Motif Chemokine Receptor 2) • CD48 (CD48 Molecule) • VCAM1 (Vascular Cell Adhesion Molecule 1)
|
Chr t(4;14)
|
Taltorvic (ridaforolimus)
2ms
IGH::NSD2 Fusion Gene Transcript as Measurable Residual Disease Marker in Multiple Myeloma. (PubMed, Cancers (Basel))
The literature lacks consensus regarding survival outcomes among patients with different NSD2 breakpoints. Our data align with previous findings indicating that patients with the MB4-2 breakpoint type tend to exhibit unfavorable overall survival.
Journal
|
NSD2 (Nuclear Receptor Binding SET Domain Protein 2)
|
Chr t(4;14)
3ms
Dissecting molecular mechanisms of immune microenvironment dysfunction in multiple myeloma and precursor conditions. (PubMed, J Cancer Metastasis Treat)
Major deregulations are found in the lymphoid compartment as well, with skewing towards immune tolerant Th17 and Treg and inhibition of CD8+ cytotoxic and CD4+ activated effector T cells. In summary, this review will provide an overview of the complex cross-talk between MM plasma cells and immune cells in the microenvironment and the molecular mechanisms promoting progression from precursor states to full-blown myeloma.
Journal
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
|
Chr t(4;14) • MYC translocation
3ms
Epigenetic dysregulation of eukaryotic initiation factor 3 subunit E (eIF3E) by lysine methyltransferase REIIBP confers a pro-inflammatory phenotype in t(4;14) myeloma. (PubMed, Haematologica)
Activation of this pathway is targetable using Ibrutinib and partially mitigated bortezomib resistance in an REIIBP xenograft model. Mechanistically, REIIBP upregulated TLR7 through eIF3E, and this relied on eIF3E RNA-binding function instead of its canonical protein synthesis activity, as demonstrated by direct binding to the 3'UTR of TLR7 mRNA. Altogether, we provided a rationale that coexistence of different NSD2 isoforms induced diversified oncogenic programs that should be considered in the strategies for t(4;14)-targeted therapy.
Journal
|
IL6 (Interleukin 6) • TLR7 (Toll Like Receptor 7) • NSD2 (Nuclear Receptor Binding SET Domain Protein 2)
|
Chr t(4;14) • Inflammatory gene signature
|
Imbruvica (ibrutinib) • bortezomib
4ms
A p53 score derived from TP53 CRISPR/Cas9 HMCLs predicts survival and reveals major role of BAX in BH3 mimetics response. (PubMed, Blood)
At the functional level, we showed that among the 13 genes, p53-regulated BAX expression correlated to, and directly impacted, the MCL1 BH3 mimetic S63845 sensitivity of myeloma cells by decreasing MCL1-BAX complexes...Nevertheless, scRNAseq analysis showed that myeloma cells surviving to the combination had lower p53 score, showing that myeloma cells with higher p53 score were more sensitive to BH3 mimetics. Taken together, we established a functional p53 score that identifies myeloma cells with biallelic TP53 invalidation, demonstrated that p53-regulated BAX is critical for optimal cell response to BH3 mimetics, and showed that MCL1 and BCL2 BH3 mimetics combination may be of interest for patients with biallelic TP53 invalidation, for whom there is still an unmet medical need.
Journal • IO biomarker
|
TP53 (Tumor protein P53) • BCL2 (B-cell CLL/lymphoma 2) • MCL1 (Myeloid cell leukemia 1) • BAX (BCL2-associated X protein)
|
Chr t(4;14) • MCL1 expression • TP53 expression • BAX expression
|
S63845
4ms
Cytogenetics in the management of multiple Myeloma: The guidelines from the Groupe Francophone de Cytogénétique Hématologique (GFCH). (PubMed, Curr Res Transl Med)
The GFCH present here the overview of genomics alterations identified in MM and related PCs diseases associated with their prognostic factor, when available, and recommendations from an expert group for identification and characterization of those alterations. This work is the update of previous 2016 recommendations.
Journal
|
TP53 (Tumor protein P53) • SDC1 (Syndecan 1)
|
Chr t(11;14) • TP53 deletion • Chr t(4;14)
4ms
ENDURANCE: Bortezomib or Carfilzomib With Lenalidomide and Dexamethasone in Treating Patients With Newly Diagnosed Multiple Myeloma (clinicaltrials.gov)
P3, N=1087, Active, not recruiting, ECOG-ACRIN Cancer Research Group | Trial primary completion date: Nov 2023 --> Nov 2025
Trial primary completion date
|
Chr t(11;14) • Chr t(4;14) • Chr t(14;16)
|
lenalidomide • bortezomib • carfilzomib
4ms
DARATUMUMAB-BORTEZOMIB-THALIDOMIDE-DEXAMETHASONE (D-VTD) IN TE-NDMM PATIENTS: A SINGLE-CENTER RETROSPECTIVE EXPERIENCE (SIE 2023)
CD34+ stem cells (SC) mobilization was performed with cyclophosphamide (2-4 g/smq) and G-CSF in 26 patients (74%) after a median time of 28 days (range: 13-50 221 Posters days) from the end of induction; 3 (11%) patients were mobilized only with G-CSF. Plerixafor on demand was administered in 13 pts (50%) failing to achieve the desired collection target...Hematological toxicity was the most common adverse event (50%; G≥3 anemia, neutropenia, thrombocytopenia occurred in 8%, 17% and 8% respectively), followed by infections (33%) and PNP (25%). In our real-life experience, D-VTD regimen was proven effective and well tolerated in TE-NDMM patients.
Retrospective data
|
CD34 (CD34 molecule)
|
Chr t(4;14) • Chr t(14;16)
|
bortezomib • cyclophosphamide • Darzalex (daratumumab) • thalidomide • plerixafor
4ms
MM-UMA PANEL, AN NGS APPROACH TO DEFINE THE MOLECULAR PROFILE OF MM PATIENTS: INTRA AND INTER LABORATORY VALIDATIONS’ RESULTS (SIE 2023)
A novel NGS targeted panel was designed and successfully validated, whose main novelty resides in the possibility to call CNAs from off-target reads, that can be used to define MM pts’ genomic risk factors, possibly required in the daily clinical practice. Thanks to AIRC IG2018-22059, AILBolognaODV.
Clinical • Next-generation sequencing
|
KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog)
|
TP53 mutation • KRAS mutation • BRAF mutation • NRAS mutation • ATM mutation • Chr t(11;14) • Chr t(4;14) • Chr t(14;16) • IGH translocation
5ms
Initial Clinical Results and Immune Correlates of a Phase 2 Study of Daratumumab, Bortezomib, Dexamethasone Followed By a Proteasome Inhibitor in-Class Transition (iCT) to Daratumumab, Ixazomib, Dexamethasone in Relapsed Refractory Multiple Myeloma (ASH 2023)
Key exclusion criteria included prior ixazomib exposure, refractoriness to anti-CD38 therapy, and refractoriness to bortezomib or carfilzomib therapy at last exposure. Treatment with DVd followed by DId with a PI iCT from bortezomib to ixazomib is a feasible approach for continuous PI and anti-CD38 therapy, leading to durable responses in RRMM pts, among whom nearly all (97%) were lenalidomide refractory. Immune correlates revealed distinct patterns of T-cell and NK-cell phenotypes when profiled serially in responding and non-responding pts. Additional correlative analyses are ongoing.
Clinical • P2 data • PD(L)-1 Biomarker • IO biomarker
|
CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • CD4 (CD4 Molecule)
|
Chr t(4;14) • Chr t(14;16)
|
lenalidomide • bortezomib • Ninlaro (ixazomib) • Darzalex (daratumumab) • carfilzomib
5ms
Final Analysis of a Phase 2 Trial of Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone in Newly Diagnosed Multiple Myeloma (NDMM) without Autologous Stem Cell Transplantation (ASCT) (ASH 2023)
34 pts (81%) underwent SC collection, all with plerixafor (median yield 8.91x106 CD34+/kg). Extended frontline Dara-KRd for NDMM without ASCT induced high rates of sCR and/or MRD(-) within 8 cycles, meeting the primary endpoint. The rate and depth of MRD(-) improved beyond C8. This ASCT-free approach led to lower PFS for pts with 2+ HRCA, as also seen with ASCT, but excellent PFS in those with standard-risk disease and 1 HRCA.
P2 data
|
CD34 (CD34 molecule)
|
Chr t(4;14) • Chr t(14;16)
|
clonoSEQ
|
lenalidomide • Darzalex (daratumumab) • carfilzomib • dexamethasone • plerixafor
5ms
Phase 1 Study of CART-Ddbcma for the Treatment of Patients with Relapsed and/or Refractory Multiple Myeloma: Results from at Least 1-Year Follow-up in All Patients (ASH 2023)
Briefly, pts with RRMM who have received ≥3 prior lines of therapy were enrolled & received a single infusion of CART-ddBCMA following lymphodepletion chemotherapy (fludarabine: 30 mg/m2/d & cyclophosphamide: 300 mg/m2/d daily for 3 days). Adverse events with CART-ddBCMA, including CRS & ICANS, were manageable & no off-tumor tissue-targeted toxicity, delayed neurotoxicity, or Parkinsonian-like events were observed in the entire cohort at the time of data-cut. Ongoing efficacy results are encouraging, with 100% ORR, including 35 (92%) response of VGPR or better & 29 (76%) with CR/sCR. More importantly, clinical responses were durable with an overall estimated 18-mo PFS rate of 67% with comparable clinical responses seen in 'high-risk' patients known to have poor prognosis.
Clinical • P1 data
|
B2M (Beta-2-microglobulin)
|
Chr t(4;14) • Chr t(14;16)
|
cyclophosphamide • fludarabine IV • anitocabtagene autoleucel (CART-ddBCMA)
5ms
Single-Cell RNA Sequencing of Circulating Tumor Cells in Precursor Myeloma Patients Reveals Mechanisms of Disease Dissemination (ASH 2023)
ConclusionsIn the largest scRNA-seq study on CTCs to date, we demonstrate the utility of CTC-based molecular profiling for prognostication of patients with early-stage disease and provide novel insights into PC circulatory potential. Additional analyses are ongoing to gain further insight into intra-patient CTC heterogeneity and define high-risk disease CTC signatures that emerge throughout the MM disease continuum.
Clinical • Circulating tumor cells • IO biomarker • Tumor cell
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CCND1 (Cyclin D1) • SDC1 (Syndecan 1) • CCND2 (Cyclin D2) • NSD2 (Nuclear Receptor Binding SET Domain Protein 2)
|
Chr t(11;14) • Chr t(4;14) • Chr t(14;16)
5ms
Phase II Trial of Daratumumab, Bortezomib, Lenalidomide and Dexamethasone in High-Risk Smoldering Multiple Myeloma (ASH 2023)
Lenalidomide has shown to delay progression in patients with high-risk smoldering multiple myeloma (HR-SMM) and curative intent trials with carfilzomib-based therapy and stem cell transplantation have been recently reported in HR-SMM leading to deep responses but with concern for treatment-related toxicities...Treatment with D-RVD is 2 years (24 cycles) with daratumumab subcutaneous (SQ) per standard dose and schedule, bortezomib 1.3mg/m2 SQ on days 1, 8, 15 for cycles 1-6 then biweekly until completion of cycle 24, lenalidomide 25mg on days 1-21 for cycles 1-6 followed by 15mg d1-21 from cycles 7-24 with weekly low dose dexamethasone... D-RVD in HR-SMM demonstrates significant activity, including a 100% ORR and high rates of MRD-negative disease, preventing progression to overt myeloma.
P2 data
|
CD34 (CD34 molecule)
|
Chr t(4;14) • Chr t(14;16)
|
lenalidomide • bortezomib • carfilzomib • Darzalex Faspro (daratumumab/hyaluronidase)
5ms
Teclistamab Induces Favorable Responses in Patients with Relapsed and Refractory Multiple Myeloma after Prior BCMA-Directed Therapy (ASH 2023)
Several studies have shown reduced efficacy of both FDA approved BCMA targeted chimeric antigen receptor T cell therapies (CAR-T) for myeloma, idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), when administered after BCMA targeted bi-specific antibodies...Tocilizumab was administered to 4 (18%) pts... This single center study in patients with heavily pretreated and prior BCMA-TT demonstrated favorable ORR (63%) and CR (36%) rates, comparable to pts in the MajesTEC-1 trial, without prior BCMA-TT exposure. No new safety signals were identified. Results on progression free survival (PFS) and overall survival (OS) will be reported with continued follow up and will be presented in the meeting.
Clinical • IO biomarker
|
Chr t(4;14) • Chr t(14;16)
|
clonoSEQ
|
Actemra IV (tocilizumab) • Abecma (idecabtagene vicleucel) • Carvykti (ciltacabtagene autoleucel) • Tecvayli (teclistamab)
5ms
Trial in Progress: A Phase 1 Study of KTX-1001, an Oral, First-in-Class, Selective MMSET Inhibitor in Patients with Relapsed and Refractory Multiple Myeloma (ASH 2023)
This Phase 1 study will evaluate a potential treatment for RRMM utilizing KTX-1001, which is a novel, first-in-class, potent, oral small-molecule MMSET inhibitor. The study is open and actively enrolling patients at centers in the United States, Spain, France, and Canada.
Clinical • P1 data • IO biomarker
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NSD2 (Nuclear Receptor Binding SET Domain Protein 2)
|
Chr t(4;14)
|
KTX-1001
5ms
Circulating Tumor Cells By Next Generation Flow Cytometry May be a New Prognostic Biomarkers Among Patients with Asymptomatic Monoclonal Gammopathies (ASH 2023)
In conclusion, CTCs are detectable in about 33% of pts with asymptomatic monoclonal gammopathies, both in MGUS (in 17%) and more frequently in SMM (in 42%) pts. Their presence is associated with a trend towards increased risk of progression to symptomatic disease for SMM, but needs longer follow up to identify the role of CTCs in MGUS and the additive information over available risk stratification tools, which could provide an non-invasive, easy-to-follow longitudinally biomarker.
Clinical • Circulating tumor cells • IO biomarker • Tumor cell
|
KIT (KIT proto-oncogene, receptor tyrosine kinase) • CD38 (CD38 Molecule) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • NCAM1 (Neural cell adhesion molecule 1) • SDC1 (Syndecan 1) • CD27 (CD27 Molecule) • CD81 (CD81 Molecule)
|
Chr t(11;14) • Chr t(4;14) • Chr t(14;16)
5ms
Differential Chromatin Organization between t(4; 14) and Non-t(4; 14) Multiple Myeloma Driven By the Histone Methyltransferase NSD2 (ASH 2023)
Systematic chromosomal re-arrangement and accessibility driven by differential epigenetic deposition of histone regulatory marks, differentiates t(4; 14) from non-t(4; 14) MM biology. These analyses suggest that given the nature of the translocation, and additionally the location of the chr4 breakpoint, result in major 3D chromosomal structural rearrangement, mediating biological programs that may explain the differences between successful and poor interventional therapies for this subset of MM disease.
Epigenetic controller
|
NSD2 (Nuclear Receptor Binding SET Domain Protein 2)
|
Chr t(4;14)
5ms
In Vivo Anti-BCMA CAR T-Cell Expansion Kinetics Correlate with Early IMWG Response in RRMM: A Single Institution Study with Comparative Analysis of Idecabtagene Vicleucel and Ciltacabtagene Autoleucel (ASH 2023)
Seven patients (30.4%) were previously treated with belantamab...Post-CAR T ferritin max correlated with the baseline b2m (p<0.001) and tocilizumab dose number (p=0.009) but none correlated with peak CAR T expansion (p=0.315)... In our single-center study of comparative analysis of commercial BCMA targeting CAR T-cell treatments, peak CAR T-cell expansion showed a positive correlation with +1 and +3 month post-CAR-T clinical responses. Despite the delayed peak expansion with ciltacel, the expansion was more robust with a higher level of circulating CAR T-cells. Baseline ALC or fludarabine dose reduction did not have an impact on overall CAR T expansion in combined cohort.
Preclinical • CAR T-Cell Therapy
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B2M (Beta-2-microglobulin)
|
Chr t(4;14)
|
fludarabine IV • Actemra IV (tocilizumab) • Abecma (idecabtagene vicleucel) • Carvykti (ciltacabtagene autoleucel)
5ms
Early Peripheral Blood Minimal Residual Disease Status By NGS in Patients with Newly Diagnosed Multiple Myeloma (MM) on a Phase 2 Trial Receiving Elotuzumab, Carfilzomib, Lenalidomide, and Dexamethasone (Elo-KRd) (ASH 2023)
MRD by NGS in the PB was less sensitive compared to the same assessment in the BM by 1-2 logs; however, PB MRD status following 4 cycles of induction therapy was strongly prognostic given its association with PFS. PB MRD status early in treatment may represent a leading indicator of early response and/or a marker of high-risk disease features, and validation of these findings may help to eventually guide intensification of therapy.
P2 data • Clinical • Next-generation sequencing • Minimal residual disease
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Chr t(4;14)
|
clonoSEQ
|
lenalidomide • carfilzomib • Empliciti (elotuzumab)
5ms
Somatic Hypermutation in Enhancer Regions Shapes Non-Coding Myeloma Genome, Generating DNA Breaks and Driving Etiology through Mutation and Structural Variation (ASH 2023)
We provide evidence for an important contribution of mutations within E and SE regions to the etiology of MM. This may involve either direct selection of mutations within the GC or by the re-entry of a memory B-cell carrying a pattern of mutations it acquired in a pre-MM phase, which then acquires a MM-specific driver. FIGURE: Distribution of mutations across MM genomes.
Tumor mutational burden
|
TMB (Tumor Mutational Burden) • CCND1 (Cyclin D1) • BCL6 (B-cell CLL/lymphoma 6) • IRF8 (Interferon Regulatory Factor 8) • NT5C (5', 3'-Nucleotidase, Cytosolic) • TENT5C (Terminal Nucleotidyltransferase 5C) • BTG2 (BTG Anti-Proliferation Factor 2) • ZFP36 (ZFP36 Ring Finger Protein)
|
Chr t(11;14) • Chr t(4;14)
5ms
Iberdomide Maintenance after Autologous Stem-Cell Transplantation in Newly Diagnosed MM: First Results of the Phase 2 EMN26 Study (ASH 2023)
In the ongoing phase 1/2 CC-220-MM-001 study, iberdomide plus dexamethasone had a favorable safety profile and demonstrated clinically meaningful activity in triple-class refractory multiple myeloma (MM) patients, including those refractory to lenalidomide and pomalidomide (IMiDs®)...All patients received a PI/IMiD-containing induction regimen which also included daratumumab in 41% of patients...Iberdomide represents a novel effective post-ASCT maintenance strategy with a favorable safety profile and superior response improvement at 6 months than what has been observed with lenalidomide maintenance (26% at 6 months in the EMN02 study). Additional follow-up is needed to define the recommended maintenance dose that will be used in the randomized phase 3 EXCALIBER maintenance study, which will evaluate iberdomide vs. lenalidomide maintenance post-ASCT.
Clinical • P2 data
|
CRBN (Cereblon)
|
Chr t(4;14) • Chr t(14;16)
|
lenalidomide • Darzalex (daratumumab) • pomalidomide • iberdomide (CC-220)
5ms
Nonmyeloablative Allogeneic Stem Cell Transplant Followed by Bortezomib in High-risk Multiple Myeloma Patients (clinicaltrials.gov)
P2, N=40, Completed, Maisonneuve-Rosemont Hospital | Active, not recruiting --> Completed
Trial completion
|
HLA-B (Major Histocompatibility Complex, Class I, B) • HLA-C (Major Histocompatibility Complex, Class I, C)
|
Chr del(17p) • Chr t(4;14) • Chr t(14;16) • Chr t(14;20) • C1As
|
bortezomib • melphalan
6ms
Selinexor, Daratumumab, Carfilzomib and Dexamethasone for the Treatment of High-Risk, Recurrent or Refractory Multiple Myeloma (clinicaltrials.gov)
P2, N=52, Recruiting, Academic and Community Cancer Research United | Trial primary completion date: Dec 2023 --> Sep 2024
Trial primary completion date
|
Chr t(4;14) • Chr t(14;16) • Chr del(1p)
|
Xpovio (selinexor) • Darzalex (daratumumab) • carfilzomib
6ms
Trial primary completion date
|
Chr t(4;14) • Chr t(14;16)
|
clonoSEQ
|
carfilzomib • pomalidomide
6ms
Discovery of NSD2-degraders from Novel and Selective DEL hits. (PubMed, Chembiochem)
Using DNA-encoded libraries, we have identified small molecule ligands that selectively and potently bind to the PWWP1 domain of NSD2, inhibit NSD2 binding to H3K36me2-bearing nucleosomes, but do not inhibit the methyltransferase activity. The ligands were subsequently converted to selective VHL1-recruiting NSD2 degraders and by using one of the most efficacious degraders in cell lines, we show that its leads to NSD2 degradation, decrease in K3K36me2 levels and inhibition of cell proliferation.
Journal
|
NSD2 (Nuclear Receptor Binding SET Domain Protein 2)
|
Chr t(4;14)
6ms
Isatuximab in Multiple Myeloma: Safety and Effectiveness (ISPOR-EU 2023)
85.7% had isatuximab in combination with carfilzomib-dexamethasone and 14.3% pomalidomide-dexamethasone...Patients had a mean of 2.8(±1,19) previous chemotherapy lines(100% on lines including bortezomib and lenalidomide)... Median PFS was not reached in our study, which prevents us from comparing the results with the pivotal trial due to the immature data. Further studies with a larger sample size and longer follow-up period are needed to confirm these real-life results. It shows a good safety and tolerability profile in our patients.
Clinical
|
FGFR3 (Fibroblast growth factor receptor 3)
|
Chr t(4;14)
|
lenalidomide • bortezomib • carfilzomib • pomalidomide • Sarclisa (isatuximab-irfc)
6ms
Combination of SKY92 gene expression profiling and cytogenetics according to R2-ISS for multiple myeloma risk stratification: the first prospective evidence (DGHO 2023)
Moreover, HR SKY92 was significantly more common in patients who received high-dose melphalan (48/89, 53.9%) than the remaining patients (9/32, 28.1%) ( P =0.01)...We found CRBN mutation in 3 out of 7 patients with only HR SKY92 but SR FISH. We provide the first prospective evidence that “double-HR” (SKY92 + FISH according to R2-ISS) indicates the highest-risk MM.
Clinical • Gene expression profiling
|
TP53 (Tumor protein P53) • CRBN (Cereblon) • SDC1 (Syndecan 1)
|
Chr t(4;14) • SDC1 positive • CRBN mutation
|
melphalan
6ms
Venetoclax Salvage Therapy in Relapsed/Refractory Multiple Myeloma (DGHO 2023)
Here we present first real world data demonstrating Ven to be an effective MM treatment option in heavily pretreated MM patients.
IO biomarker
|
TP53 (Tumor protein P53)
|
TP53 mutation • Chr t(11;14) • TP53 mutation + Chr del(17p) • Chr t(4;14) • Chr t(14;16) • BCL2 expression
|
Venclexta (venetoclax)
6ms
Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone for the Treatment of High-Risk Newly Diagnosed Multiple Myeloma. (PubMed, J Clin Oncol)
Isa-KRd effectively induces high rates of sustainable MRD negativity in the difficult-to-treat HRNDMM population, regardless of transplant status, translating into a median PFS that was not yet reached after 44/33 months.
Journal
|
Chr t(4;14) • Chr t(14;16)
|
lenalidomide • carfilzomib • Sarclisa (isatuximab-irfc) • melphalan
7ms
Multiparametric Flow Cytometry in Newly Diagnosed Multiple Myeloma Patients: An Italian Monocentric Experience. (PubMed, Mediterr J Hematol Infect Dis)
The results of this study indicate that in the diagnostic work-up of MM, MFC may help to identify different patient subsets and improve risk stratification. These observations need to be validated in larger series of patients with a longer follow-up.
Journal
|
KIT (KIT proto-oncogene, receptor tyrosine kinase) • CD20 (Membrane Spanning 4-Domains A1) • CD33 (CD33 Molecule) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • NCAM1 (Neural cell adhesion molecule 1) • SDC1 (Syndecan 1) • ANPEP (Alanyl Aminopeptidase, Membrane)
|
Chr t(4;14) • Chr t(14;16) • CD20 expression • SDC1 positive • SDC1 expression
7ms
Natural history, predictors of development of extramedullary disease, and treatment outcomes for patients with extramedullary multiple myeloma. (PubMed, Am J Hematol)
In a matched cohort, multivariate logistic regression analysis demonstrated younger age at diagnosis, 1q duplication, and t(4;14) at diagnosis of MM to be independent predictors of development of secondary EMM. Presence of EMM was independently associated with inferior OS in the matched cohorts for both de novo (HR 2.9 &lsqb;95% CI: 1.6-5.4], p = .0007) and secondary EMM (HR 1.5 &lsqb;95% CI: 1.1-2], p = .001).
Retrospective data • Journal
|
Chr t(4;14)
7ms
Quantitative Analysis of Whole-Body MRI for Accessing the Degree of Diffuse Infiltration Patterns and Identifying High Risk Cases of Newly Diagnosed Multiple Myeloma. (PubMed, J Magn Reson Imaging)
Compared with qualitative analysis, FF value was independently associated with HRMM. The quantitative features of diffuse marrow infiltration on MRI scans are more effective in detecting HRMM.
Journal
|
TP53 (Tumor protein P53) • B2M (Beta-2-microglobulin)
|
TP53 mutation • Chr t(4;14) • Chr t(14;16)
7ms
Quantification of cyclin D1 and D2 proteins in multiple myeloma identifies different expression patterns from those revealed by gene expression profiling. (PubMed, Haematologica)
In conclusion, although one of the cyclins D is overexpressed at the mRNA level in almost all MM patients, in approximately half of the patients this does not translate into detectable protein. This suggests that cyclins D could not play an oncogenic role in a proportion of patients with MM.
Journal
|
CCND1 (Cyclin D1) • CCND2 (Cyclin D2)
|
Chr t(11;14) • Chr t(4;14) • Chr t(14;16) • CCND1 expression • CCND1-H
7ms
CircRNAs in diagnosis, prognosis, and clinicopathological features of multiple myeloma; a systematic review and meta-analysis. (PubMed, Cancer Cell Int)
Our meta-analysis demonstrates that the expression analysis of circRNAs is valuable for MM's diagnosis and prognosis determination. Also, dysregulation of circRNAs is associated with poor clinicopathological features and can be used as the applicable biomarkers for evaluating treatment effectiveness.
Retrospective data • Review • Journal
|
B2M (Beta-2-microglobulin)
|
Chr t(4;14)
7ms
Pembrolizumab + Lenalidomide Post Autologous Stem Cell Transplant (ASCT) in High-risk Multiple Myeloma (MM) (clinicaltrials.gov)
P2, N=12, Terminated, Hackensack Meridian Health | Active, not recruiting --> Terminated; FDA Hold Due to Updated Risks
Trial termination
|
TP53 (Tumor protein P53)
|
TP53 deletion • Chr t(4;14) • Chr t(14;16)
|
Keytruda (pembrolizumab) • lenalidomide • melphalan
8ms
Daratumumab, Cyclophosphamide, Bortezomib, Lenalidomide, and Dexamethasone as Induction and Extended Consolidation Improves Outcome in Ultra-High-Risk Multiple Myeloma. (PubMed, J Clin Oncol)
Our results suggest that Dara-CVRd induction and extended post-ASCT Dara-VRd consolidation markedly improve PFS for UHiR NDMM patients over conventional management, supporting further evaluation of this strategy.
Journal
|
Chr t(4;14) • Chr t(14;16) • Chr del(1p)
|
lenalidomide • bortezomib • cyclophosphamide • Darzalex (daratumumab) • carfilzomib
8ms
Belantamab Mafodotin, Pomalidomide and Dexamethasone for the Treatment of High-Risk Myeloma (clinicaltrials.gov)
P2, N=34, Recruiting, Emory University | Trial completion date: Oct 2024 --> Oct 2025
Trial completion date
|
CD4 (CD4 Molecule)
|
Chr t(4;14) • Chr t(14;16)
|
pomalidomide • Blenrep (belantamab mafodotin-blmf) • Hemady (dexamethasone tablets)