Early Relapse Risk in Patients with Newly Diagnosed Multiple Myeloma Characterized by Next-generation Sequencing

D’Agostino, Mattia; Zaccaria, Gian Maria; Ziccheddu, Bachisio; Rustad, Even H.; Genuardi, Elisa; Capra, Andréa; Oliva, Stefania; Auclair, Daniel; Yesil, Jennifer; Colucci, Paola; Gambella, Manuela; Bringhen, Sara; Larocca, Alessandra; Boccadoro, Mario; Bolli, Niccolò; Maura, Francesco

doi:10.1158/1078-0432.ccr-20-0951

Cited by 43 publications

(37 citation statements)

References 39 publications

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“…IGLL5 located within the immunoglobulin lambda locus encoded one of the IGLLs, which were the immunoglobulin lambda joining 1 and the immunoglobulin lambda constant 1 gene segments. Only a limited number of research has shown that IGLL5 has a frequent mutation in chronic lymphocytic leukemia [33,34], lymphoma [35][36][37], and multiple myeloma [38,39]; besides, IGLL5 has a prognostic value in several diseases, such as multiple myeloma and glioblastoma [39][40][41]. Moreover, previous studies have shown that IGLL5 has a prognostic value in ccRCC, while no in-depth study has concentrated on TICs.…”

Section: Discussionmentioning

confidence: 99%

IGLL5 is correlated with tumor‐infiltrating immune cells in clear cell renal cell carcinoma

et al. 2021

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Renal cell carcinomas (RCCs) account for about 90% of renal tumors, and their major histological subtype is ccRCC (clear cell RCC). Increasing evidence has indicated that the tumor microenvironment plays a significant role in the occurrence and development of ccRCC. In this study, we used ESTIMATE and CIBERSORT computational methods to calculate the proportion of immune and stromal components and the rate of TICs (tumor‐infiltrating immune cells) in 539 ccRCC samples from The Cancer Genome Atlas database. By examining the intersection of the differentially expressed genes obtained by the protein–protein interaction network and Cox regression analysis, we identified only one overlapping gene: IGLL5 (immunoglobulin lambda‐like polypeptide 5). We report that IGLL5 expression is correlated with TICs. Furthermore, our immunoinfiltration analyses revealed that three types of TIC are positively correlated with IGLL5 expression. IGLL5 may have potential as a prognostic biomarker of ccRCC.

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Section: Discussionmentioning

confidence: 99%

IGLL5 is correlated with tumor‐infiltrating immune cells in clear cell renal cell carcinoma

et al. 2021

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“…In a multivariate analysis, D'Agostino et al showed that mutation of P53 was correlated with early relapse in MM patients. In addition, the study showed that patients with both, deletion of the 17p and P53 mutations, have a shorter OS compared to patients with only one chromosomal aberration [15]. An increased risk of acquired P53 mutation was also observed in patients carrying a deletion of 17p [15].…”

Section: Introductionmentioning

confidence: 89%

Role of 1q21 in Multiple Myeloma: From Pathogenesis to Possible Therapeutic Targets

Burroughs‐Garcia

Eufemiese

Storti

et al. 2021

Cells

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Multiple myeloma (MM) is characterized by an accumulation of malignant plasma cells (PCs) in the bone marrow (BM). The amplification of 1q21 is one of the most common cytogenetic abnormalities occurring in around 40% of de novo patients and 70% of relapsed/refractory MM. Patients with this unfavorable cytogenetic abnormality are considered to be high risk with a poor response to standard therapies. The gene(s) driving amplification of the 1q21 amplicon has not been fully studied. A number of clear candidates are under investigation, and some of them (IL6R, ILF2, MCL-1, CKS1B and BCL9) have been recently proposed to be potential drivers of this region. However, much remains to be learned about the biology of the genes driving the disease progression in MM patients with 1q21 amp. Understanding the mechanisms of these genes is important for the development of effective targeted therapeutic approaches to treat these patients for whom effective therapies are currently lacking. In this paper, we review the current knowledge about the pathological features, the mechanism of 1q21 amplification, and the signal pathway of the most relevant candidate genes that have been suggested as possible therapeutic targets for the 1q21 amplicon.

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“…For instance, intermediate-fit or frail patients may safely receive naked mAbs or ADCs, but they are unlikely to tolerate BiAbs or CAR T-cell therapy. On the other hand, fit patients who present with high-risk disease or who experienced early relapse after first-line treatment may benefit from BiAbs or CAR T-cell therapy [101]. As with anti-CD38 therapies, the mechanisms of resistance to anti-BCMA agents may shed light on the optimal treatment sequencing.…”

Section: Future Directions and Conclusionmentioning

confidence: 99%

Monoclonal Antibodies to Treat Multiple Myeloma: A Dream Come True

D’Agostino

Innorcia

Boccadoro

et al. 2020

IJMS

Self Cite

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Immunotherapy is increasingly used in the treatment of multiple myeloma (MM). Monoclonal antibodies (mAbs) are safe and effective ways to elicit immunotherapeutic responses. In 2015, daratumumab has become the first mAb approved by the Food and Drug Administration for clinical use in MM and, in the last 5 years, a lot of clinical and preclinical research has been done to optimize the use of this drug class. Currently, mAbs have already become part of standard-of-care combinations for the treatment of relapsed/refractory MM and very soon they will also be used in the frontline setting. The success of simple mAbs (‘naked mAbs’) prompted the development of new types of molecules. Antibody–drug conjugates (ADCs) are tumor-targeting mAbs that release a cytotoxic payload into the tumor cells upon antigen binding in order to destroy them. Bispecific antibodies (BiAbs) are mAbs simultaneously targeting a tumor-associated antigen and an immune cell-associated antigen in order to redirect the immune cell cytotoxicity against the tumor cell. These different constructs produced solid preclinical data and promising clinical data in phase I/II trials. The aim of this review article is to summarize all the recent developments in the field, including data on naked mAbs, ADCs and BiAbs.

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Early Relapse Risk in Patients with Newly Diagnosed Multiple Myeloma Characterized by Next-generation Sequencing

Cited by 43 publications

References 39 publications

IGLL5 is correlated with tumor‐infiltrating immune cells in clear cell renal cell carcinoma

IGLL5 is correlated with tumor‐infiltrating immune cells in clear cell renal cell carcinoma

Role of 1q21 in Multiple Myeloma: From Pathogenesis to Possible Therapeutic Targets

Monoclonal Antibodies to Treat Multiple Myeloma: A Dream Come True

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