ABSTRACT
BACKGROUND: The plasma cell malignancy, multiple myeloma (MM), remains incurable despite advanced treatment protocols. Overexpression of Bcl-2 (an anti-apoptotic protein), in MM harboring the translocation (11;14), contributes to resistance to prior therapy. Venetoclax, a selective oral inhibitor of BCL-2 is a novel agent that shows promise as a therapeutic agent. AIMS: The objective of this systematic review is to address how the use of venetoclax, alone or as a combination regimen, contributed to the treatment of patients with t(11:14) positive relapsed/refractory multiple myeloma (RRMM). DATA SOURCES: This systematic review was conducted in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was done on 5th June 2022. A literature search was conducted on PubMed and Scopus, 145 articles were screened and 10 studies were included. Risk of bias assessment was performed using the Methodological Index for Non-Randomized Studies (MINORS) criteria. DATA SUMMARY: Across the studies reviewed, a total of 311 patients were identified with t(11;14) positive RRMM. The overall response rate achieved ranged between 33% and 95.5%. Furthermore, the use of venetoclax has exhibited a favorable adverse effect profile. Side effects included hematological side effects, nausea, vomiting, and diarrhea. CONCLUSION: Venetoclax demonstrates promising results. When given with drugs like dexamethasone, daratumumab and carfilzomib, a synergistic effect is seen in treating translocation (11:14) positive relapsed/refractory MM. The use of venetoclax in clinical practice can potentially improve outcomes and quality of life in RRMM patients, and future research should continue to explore this promising treatment option.
Subject(s)
Bridged Bicyclo Compounds, Heterocyclic , Multiple Myeloma , Sulfonamides , Humans , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bridged Bicyclo Compounds, Heterocyclic/therapeutic use , Bridged Bicyclo Compounds, Heterocyclic/administration & dosage , Bridged Bicyclo Compounds, Heterocyclic/adverse effects , Chromosomes, Human, Pair 11/genetics , Chromosomes, Human, Pair 14/genetics , Drug Resistance, Neoplasm , Multiple Myeloma/drug therapy , Multiple Myeloma/genetics , Neoplasm Recurrence, Local/drug therapy , Sulfonamides/therapeutic use , Sulfonamides/administration & dosage , Translocation, GeneticABSTRACT
Background: IRF2BPL (interferon regulatory factor 2-binding protein-like) gene is an intronless gene present ubiquitously in the human body, including the brain. Pathogenic variants lead to neurodegeneration and present with phenotypic features of a neurological disorder, including dyslexia, dyscalculia, epilepsy, dystonia, neurodevelopmental regression, loss of motor skills and cerebellar ataxia. Case: We present a case of a 9-year-old boy who was brought to the emergency department with generalised tonic-clonic seizures and mild hypotonia. A history included neurological regression. After insignificant lab and imaging results, the patient underwent genetic testing, revealing a novel pathogenic mutation in the IRF2BPL gene (heterozygous variant), which had never been reported in the literature before. An autosomal dominant loss of function mutation was demonstrated, denoting in DNA as NM_0 24 496 c.911 C>T, which results in premature protein termination (p.Glu494). Conclusion: Our case highlights the importance of early recognition of the neurological symptoms associated with various IRF2BPL gene mutations so that a timely multidisciplinary management approach can be provided.
