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Venetoclax Effectively Targets B-Cell Multiple Myeloma

Venetoclax Effectively Targets B-Cell Multiple Myeloma
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Published on March 8, 2021

The Role of Venetoclax in Treating B-Cell Myeloma

The introduction of several new treatments for people with multiple myeloma has resulted in an increase in the number of effective combination therapies, including immunotherapies, resulting in a significant improvement in median overall survival (OS). This is a huge step from years ago when there were few treatments available for myeloma, which is a cancer of the plasma cells, a type of white blood cell found in the bone marrow. Multiple myeloma is a rare cancer; approximately 34,920 people (19,320 men and 15,600 women) will be diagnosed with it this year, according to the American Cancer Society.

Venetoclax (Venclexta), an oral tablet medication that was first approved by the FDA in 2016, became available on the market in recent years for treating diseases like chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML). The use of this therapy is expanding, and it has shown to be very effective in treating 11 of the 14 subtypes of multiple myeloma. Venetoclax is a mechanism of action that targets and programs apoptosis, a fancy term for cell death. Experts are excited about this drug because it appears to be effective against B-cell subtypes of myeloma.

Researchers from the Winship Cancer Institute of Emory University wanted to identify factors contributing to venetoclax response, so Dr. Vikas A Gupta and colleagues studied a panel of 31 myeloma cell lines and 25 patient samples tested for venetoclax sensitivity. What they discovered is that venetoclax sensitivity in multiple myeloma is associated with B cell gene expression.1 This is good news for patients with this subtype of myeloma. It means that this therapy is effective in creating cell death.

Venetoclax Side Effects

Venetoclax is not without potential side effects such as neutropenia (low white blood cell count), anemia (low iron levels), and to a lesser extent some gastrointestinal troubles such as diarrhea, nausea, constipation, vomiting and fatigue.

People with B-cell malignancies like myeloma show elevated levels of circulating B-cell maturation antigen (BCMA), a cell surface protein that has emerged as a selective antigen in newer treatments for myeloma. This is light years away from the early days of multiple myeloma where very few therapies were available.

Venetoclax Combined with Atezolizumab

Additionally, venetoclax may be effective when used with other therapeutic agents, such as atezolizumab (Tecentriq), as demonstrated in an early, small study of 49 patients with relapsed or refractory multiple myeloma.Future studies will paint a clearer picture of the value, efficacy and safety of this drug combination, so stay tuned for upcoming news later this year or near year-end.

B-Cell Biomarker Used to Predict Outcomes in Myeloma

A study by Dr. Michael Ghermezi and colleagues at the Institute for Myeloma & Bone Cancer Research in California demonstrated that B cells can predict outcomes for patients, which is amazing because multiple myeloma develops and responds to newer therapies quite well. 

Blood serum was collected from 243 patients from a single clinic that specializes in the treatment of myeloma. Results demonstrated that serum B-cell maturation antigen (sBCMA) levels were higher among smoldering and untreated active patients with myeloma than healthy donors.3 Smoldering myeloma is a precancerous condition that can, but does not always, lead to full-blown myeloma. It’s often symptom-free but can lead to things like anemia, which people say makes them very tired and can be treated easily with iron.

The study shows that the elevated sBCMA levels experienced by myeloma patients can be used to follow their disease status, progression-free survival and overall survival. The research team recommended additional studies to further explore the role of sBCMA in treating patients with myeloma.

Having a tool to predict outcomes can improve personalized therapy for patients so that they get the right treatment at the right time, just for them.

~Lauren Evoy Davis

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1Gupta VA, Barwick BG, Matulis SM, et al. Venetoclax sensitivity in multiple myeloma is associated with B cell gene expression. Blood. March 1, 2021.

2Schjesvold1 F, Ribrag V, Paula Rodriguez-Otero P, et al. 295 Safety and Preliminary Efficacy Results from a Phase Ib/II Study of Cobimetinib As a Single Agent and in Combination with Venetoclax with or without Atezolizumab in Patients with Relapsed/Refractory Multiple Myeloma. ASH2020. (abstract 295).

3Ghermezi M, Li M, Vardanyan S, et al. Serum B-cell maturation antigen: a novel biomarker to predict outcomes for multiple myeloma patients. Haematologica. 2017 Apr; 102(4): 785–795.

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