Role of Daratumumab in Combination With Standard Therapies in Patients With Relapsed and Refractory Multiple Myeloma

Bapatla, Anusha; Kaul, Arunima; Dhalla, Paramvijay Singh; Armenta-Quiroga, Ana S; Khalid, Raheela; Garcia, Jian; Khan, Safeera

doi:10.7759/cureus.15440

Cited by 3 publications

(1 citation statement)

References 29 publications

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“…At the same time, SLAMF7 is thought to play a role In BM stromal interactions with MMPCs to promote survival and is also highly expressed by all stages of MMPCs [294,295]. The landmark advancement in MM therapy was the development and approval of the monoclonal antibodies elotuzumab (anti-SLAMF7) and daratumumab (anti-CD38) in 2015 for both monotherapy and combination forms, particularly in the case of RRMM [296][297][298][299][300][301]. The first anti-BCMA CAR-T cells were made by lentiviral vector-mediated transfection in 2013 using a single-chain variable fragment from mouse anti-BCMA antibody combined with hinge and transmembrane regions of human CD8α, CD3ζ T-cell activation domain, and a costimulatory molecule (CD28), and the first clinical trial took place in 2016 to show potent cytotoxicity in refractory MM [302,303].…”

Section: Immunotherapy In Multiple Myelomamentioning

confidence: 99%

Good Cop, Bad Cop: Profiling the Immune Landscape in Multiple Myeloma

Sharma,

Choudhary

2023

Biomolecules

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Multiple myeloma (MM) is a dyscrasia of plasma cells (PCs) characterized by abnormal immunoglobulin (Ig) production. The disease remains incurable due to a multitude of mutations and structural abnormalities in MM cells, coupled with a favorable microenvironment and immune suppression that eventually contribute to the development of drug resistance. The bone marrow microenvironment (BMME) is composed of a cellular component comprising stromal cells, endothelial cells, osteoclasts, osteoblasts, and immune cells, and a non-cellular component made of the extracellular matrix (ECM) and the liquid milieu, which contains cytokines, growth factors, and chemokines. The bone marrow stromal cells (BMSCs) are involved in the adhesion of MM cells, promote the growth, proliferation, invasion, and drug resistance of MM cells, and are also crucial in angiogenesis and the formation of lytic bone lesions. Classical immunophenotyping in combination with advanced immune profiling using single-cell sequencing technologies has enabled immune cell-specific gene expression analysis in MM to further elucidate the roles of specific immune cell fractions from peripheral blood and bone marrow (BM) in myelomagenesis and progression, immune evasion and exhaustion mechanisms, and development of drug resistance and relapse. The review describes the role of BMME components in MM development and ongoing clinical trials using immunotherapeutic approaches.

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Section: Immunotherapy In Multiple Myelomamentioning

confidence: 99%

Good Cop, Bad Cop: Profiling the Immune Landscape in Multiple Myeloma

Sharma,

Choudhary

2023

Biomolecules

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Plasma cell neoplasms, multiple myeloma, solitary plasmocytoma a plasma cell leukemia. Clinical symptoms, diagnostic criteria and therapy

Adam¹,

Pour²,

Krejčí³

et al. 2022

Onkologie

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Plazmocelulární malignity (mnohočetný myelom, solitární Plazmocytom a Plazmocelulární leukemie), Přehled klinických Příznaků, diagnostických kritérií a léčby Working Group definuje PCL přítomností 5 % či více cirkulujících plazmatických buněk detekovatelných při cytologickém hodnocení nátěru periferní krve u pacientů s mnohočetným myelomem. V textu jsou probrány příznaky, diagnostická kritéria a léčba těchto tří chorob spadajících pod skupinové označení plazmocelulární malignity.Klíčová slova: mnohočetný myelom, solitární plazmocytom, plazmocelulární leukemie, daratumumab, transplantace krvetvorné tkáně. Plasma cell neoplasms, multiple myeloma, solitary plasmocytoma a plasma cell leukemia. Clinical symptoms, diagnostic criteria and therapyAccording the WHO classification of malignant hematologic diseases the group plasma cell neoplasms consists of multiple myeloma, solitary plasmocytoma and plasmocytic leukemia. Diagnosis of multiple myeloma requires ≥10% clonal bone marrow plasma cells or a biopsy proven plasmacytoma plus evidence of one or more multiple myeloma defining events (MDE) namely CRAB (hypercalcemia, renal failure, anemia, or lytic bone lesions) features felt related to the plasma cell disorder, bone marrow clonal plasmacytosis ≥60%, serum involved/uninvolved free light chain (FLC) ratio ≥100 (provided involved FLC is ≥100 mg/L), or >1 focal lesion on magnetic resonance imaging (MRI). The presence of del(17p), t(4;14), t(14;16), t(14;20), gain 1q, or p53 mutation is considered high-risk multiple myeloma. Presence of any two high risk factors is considered double-hit myeloma; three or more high risk factors is triple-hit myeloma. Solitary plasmacytoma is an infrequent form of plasma cell dyscrasia that presents as a single mass of monoclonal plasma cells, located either extramedullary or intraosseous. In some patients, a bone marrow aspiration can detect a low monoclonal plasma cell infiltration which indicates a high risk of early progression to an overt myeloma disease. Before treatment initiation, whole body positron emission tomography-computed tomography or magnetic resonance imaging should be performed to exclude the presence of additional malignant lesions. For decades, treatment has been based on radiation, but studies exploring the potential benefit of systemic therapies for high-risk patients are urgently needed, becouse in solitary plasmocytomas of diameter more the 5 cm is the response to radioterapie often incomplete. Primary plasma cell leukemia (PCL) has a consistently ominous prognosis, even after progress in the last decades. PCL deserves a prompt identification to start the most effective treatment for this ultra-high-risk disease. The aim of this position paper is to revisit the diagnosis of PCL according to the presence of circulating plasma cells in patients otherwise meeting diagnostic criteria of multiple myeloma. The presence of ≥5% circulating plasma cells in patients with MM had a similar adverse prognostic impact as the previously defined PCL by more the 20% ciculating plasma...

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Review of daratumumab efficacy in all monoclonal gammopathies and other diseases and our experience with daratumumab, lenalidomide and dexamethasone therapy in 74 patients

Adam¹,

Pour²,

Krejčí³

et al. 2022

Onkologie

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Review of daratumumab efficacy in all monoclonal gammopathies and other diseases and our experience with daratumumab, lenalidomide and dexamethasone therapy in 74 patientsMultiple myeloma (MM) is a hematological malignancy characterized by renal insufficiency, bone lesions, anaemia, and hypercalcemia. In this modern era of medicine, even with the development of drugs like immunomodulatory drugs (IMiDs) and proteasome inhibitors (PI), the treatment of MM prevails as a challenge. However, even after the attainment of total remission, relapse of MM and disease progression is frequent. That is why there is an urgent requirement to develop novel monoclonal antibody drugs. The latest drugs for the treatment of relapsed and refractory MM (RRMM) approved by the Food and Drug Administration (FDA) is daratumumab. In this article, we will discuss daratumumab with different combination therapies in multiple myeloma, but also in other indications. Information about the efficacy in various type of Monoclonal Gammopathy of Clinical Significance are reviewed. Several studies tested daratumumab in autoimmune diseases with positive results. The goal of this publication is to give information about all indication in which daratumumab was tested with positive results. And we alsou inform about our own experiencies with daratumumab, lenalidomide dexamethasone in 74 pacients treated in the year 2018-2021.

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Role of Daratumumab in Combination With Standard Therapies in Patients With Relapsed and Refractory Multiple Myeloma

Cited by 3 publications

References 29 publications

Good Cop, Bad Cop: Profiling the Immune Landscape in Multiple Myeloma

Good Cop, Bad Cop: Profiling the Immune Landscape in Multiple Myeloma

Plasma cell neoplasms, multiple myeloma, solitary plasmocytoma a plasma cell leukemia. Clinical symptoms, diagnostic criteria and therapy

Review of daratumumab efficacy in all monoclonal gammopathies and other diseases and our experience with daratumumab, lenalidomide and dexamethasone therapy in 74 patients

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