Role of Venetoclax in the Treatment of Relapsed and Refractory Multiple Myeloma

Ehsan, Hamid; Wahab, Ahsan; Shah, Zunairah; Sana, Muhammad Khawar; Masood, Adeel; Rafae, Abdul; Hashmi, Hamza

doi:10.14740/jh844

Cited by 6 publications

(6 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Venetoclax is a diminutive molecule inhibitor that specifically targets BCL-2, an antiapoptotic protein that is frequently overexpressed in multiple myeloma cells [222]. The medication has been authorized for the management of relapsed or refractory multiple myeloma in conjunction with other drugs by inducing apoptosis [223]. It is noteworthy that the domain of multiple myeloma is subject to persistent research and development, with the emergence of novel therapeutic agents that target specific protein signatures.…”

Section: Therapeutic Agents To Target Protein Signaturesmentioning

confidence: 99%

Proteomic Alteration in the Progression of Multiple Myeloma: A Comprehensive Review

et al. 2023

View full text Add to dashboard Cite

Multiple myeloma (MM) is an incurable hematologic malignancy. Most MM patients are diagnosed at a late stage because the early symptoms of the disease can be uncertain and nonspecific, often resembling other, more common conditions. Additionally, MM patients are commonly associated with rapid relapse and an inevitable refractory phase. MM is characterized by the abnormal proliferation of monoclonal plasma cells in the bone marrow. During the progression of MM, massive genomic alterations occur that target multiple signaling pathways and are accompanied by a multistep process involving differentiation, proliferation, and invasion. Moreover, the transformation of healthy plasma cell biology into genetically heterogeneous MM clones is driven by a variety of post-translational protein modifications (PTMs), which has complicated the discovery of effective treatments. PTMs have been identified as the most promising candidates for biomarker detection, and further research has been recommended to develop promising surrogate markers. Proteomics research has begun in MM, and a comprehensive literature review is available. However, proteomics applications in MM have yet to make significant progress. Exploration of proteomic alterations in MM is worthwhile to improve understanding of the pathophysiology of MM and to search for new treatment targets. Proteomics studies using mass spectrometry (MS) in conjunction with robust bioinformatics tools are an excellent way to learn more about protein changes and modifications during disease progression MM. This article addresses in depth the proteomic changes associated with MM disease transformation.

show abstract

Section: Therapeutic Agents To Target Protein Signaturesmentioning

confidence: 99%

Proteomic Alteration in the Progression of Multiple Myeloma: A Comprehensive Review

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Our patient was treated upfront with CyBorD in combination with daratumumab, providing a short-lived clinical response lasting approximately 4 months. For patients harboring chromosomal translocation t(11;14), venetoclax demonstrates promising activity in terms of overall response rate and progression-free survival, both alone or in a combined regimen [ 26 – 28 ]. In our case, venetoclax was used in the relapsed/refractory setting; however, this agent did not overcome the high-risk features of his disease.…”

Section: Discussionmentioning

confidence: 99%

Non-producer multiple myeloma presenting with acute hyperammonemic encephalopathy: case report

et al. 2023

View full text Add to dashboard Cite

Background Hyperammonemic encephalopathy (HE) is a rare and life-threatening complication of multiple myeloma, with underlying mechanisms that are not fully understood. In contrast to previously reported cases, most of which have been associated with IgG or IgA isotypes, we describe a patient with HE as the presenting symptom of non-producer multiple myeloma (NPMM). Case presentation A 60-year-old man developed lethargy that progressed into coma. He was found to have an elevated ammonia level, despite normal hepatic function. He was diagnosed with HE secondary to NPMM, demonstrating 80% plasma cells without light chain expression in the bone marrow and absence of a monoclonal protein in the serum or urine, including by matrix-assisted laser desorption ionization time-of-flight mass-spectrometry (MASS-FIX). Myeloma-directed therapy with daratumumab, bortezomib, cyclophosphamide and dexamethasone successfully reversed his HE. At clinical relapse, he received salvage chemotherapy followed by venetoclax therapy, leading to a short period of neurological recovery. Conclusions This case demonstrates that HE can occur in a patient with NPMM and challenges the mechanism suggested by limited prior studies; i.e., that excess ammonia in multiple myeloma arises from degradation of M-proteins. We postulate that the neoplastic plasma cells in NPMM have amplified amino acid metabolism, despite lacking detectable intracellular or secreted immunoglobulins.

show abstract

“…B-cell lymphoma-2 (BCL-2) protein is an antiapoptotic protein expressed on clonal plasma cells in patients with MM [75]. Venetoclax is a highly selective, potent, oral BCL-2 inhibitor that can induce apoptosis in MM cells [76].…”

Section: Venetoclax In the Treatment Of MMmentioning

confidence: 99%

“…Venetoclax is a highly selective, potent, oral BCL-2 inhibitor that can induce apoptosis in MM cells [76]. MM subsets with t11,14 have overexpression of BCL-2 and can benefit from venetoclax when used either alone or in combination with other chemotherapeutic agents with an overall response rate of 40-100% [75]. However, the following side effects have been reported: gastrointestinal disturbances, cytopenias, infectious complications, and death [75,76].…”

Section: Venetoclax In the Treatment Of MMmentioning

confidence: 99%

“…MM subsets with t11,14 have overexpression of BCL-2 and can benefit from venetoclax when used either alone or in combination with other chemotherapeutic agents with an overall response rate of 40-100% [75]. However, the following side effects have been reported: gastrointestinal disturbances, cytopenias, infectious complications, and death [75,76]. Venetoclax and dexamethasone combination has demonstrated efficacy and manageable safety in heavily pretreated patients with RR-MM having t11,14 [77].…”

Section: Venetoclax In the Treatment Of MMmentioning

confidence: 99%

See 1 more Smart Citation

Multiple Myeloma in the Era of Novel Agents and Stem Cell Therapies

Al-Anazi¹

2023

Recent Updates on Multiple Myeloma

View full text Add to dashboard Cite

The recent availability of several lines of novel therapeutic agents such as immunomodulatory agents, proteasome inhibitors, and monoclonal antibodies; the widespread utilization of hematopoietic stem cell transplantation; the use of advanced diagnostic techniques that allow risk stratification and monitoring of treatment responses; and the general improvement in health care have revolutionized treatment of patients with multiple myeloma and this has translated into significant improvements in survival outcomes. Monitoring of minimal residual disease can guide the intensity of treatment, and the efficient application of modern diagnostic tools in monitoring treatment responses in real-world clinical practice can hopefully be achieved in the near future. The recent use of quadruplet regimens in the treatment of patients with multiple myeloma has translated into unprecedented treatment responses and survival outcomes. Also, chimeric antigen receptor T-cell therapy and bispecific antibodies represent a new dimension in the precision medicine in MM. Additionally, our ability to induce deep responses has improved, and the treatment goal in myeloma patients tolerating the recommended therapy has moved from delay of disease progression to induction of the deepest possible response.

show abstract

Role of Venetoclax in the Treatment of Relapsed and Refractory Multiple Myeloma

Cited by 6 publications

References 25 publications

Proteomic Alteration in the Progression of Multiple Myeloma: A Comprehensive Review

Proteomic Alteration in the Progression of Multiple Myeloma: A Comprehensive Review

Non-producer multiple myeloma presenting with acute hyperammonemic encephalopathy: case report

Multiple Myeloma in the Era of Novel Agents and Stem Cell Therapies

Contact Info

Product

Resources

About