Efficacy of Venetoclax and Dexamethasone in Refractory IgM Primary Plasma Cell Leukemia with t(11;14) and TP53 Mutation: A Case Report and Literature Review

Abstract

Primary plasma cell leukemia (pPCL) is an uncommon disease. IgM multiple myeloma (MM) is an infrequent subtype that accounts for less than 1 percent of MM cases. IgM pPCL is quite rare with only a few cases published to date. We describe a case of a patient with IgM pPCL who initially presented with hyperviscosity syndrome requiring urgent plasma exchange. His bone marrow biopsy demonstrated t(11;14). He progressed on proteasome inhibitors, immunomodulating agents, and other chemotherapy medications but later achieved very good partial response (VGPR) to venetoclax and dexamethasone. Given the poor prognosis of pPCL, further studies using venetoclax alone or in combination with other novel agents as first-line treatment options are warranted particularly in patients with t(11;14).

Complete response following treatment of plasma cell leukemia with venetoclax and dexamethasone: A case report

“…[10][11][12] Several published case reports have supported the use of venetoclax as a treatment agent for PCL as monotherapy or as part of a combination regimen. [13][14][15][16][17][18][19] The following case reinforces the effectiveness of venetoclax use in the setting of PCL, but additionally illustrates its potential to induce complete remission as a bridge toward consolidation with autologous SCT.…”

“…The t (11;14) translocation is a cytogenetic abnormality that occurs more frequently in PCL than in MM and may serve as a predictive biomarker for venetoclax. 16 Findings from the BELLINI trial suggested that patients with t (11;14) and high BCL2 expression have a favorable outcome with venetoclax, further highlighting that biomarker-driven treatment strategies is a possible approach for t(11;14) PCL patients. Although the mechanism of venetoclax has not been fully elucidated, it is thought that high expression of BCL-2 plays a pivotal role in tumor growth and survival, making venetoclax's unique mechanism in targeting this intrinsic apoptotic pathway a favorable therapy option.…”

Transcriptomic Analysis in Multiple Myeloma and Primary Plasma Cell Leukemia with t(11;14) Reveals Different Expression Patterns with Biological Implications in Venetoclax Sensitivity

“…Indeed, despite possessing the hallmarks of terminally differentiated PCs, venetoclax sensitive MMs retain or aberrantly reactivate aspects of the B-cell program, including BCL2 dependence, along with other specific patterns of B-cell gene expression and chromatin accessibility, and point to novel biomarkers of venetoclax sensitive MM independent of t(11;14) [ 19 ]. Currently, there are very little data from case reports on the efficacy of venetoclax in pPCL with t(11;14) [ 26 , 35 , 36 , 37 ], and defining a specific predictor of venetoclax sensitivity is challenging. Our study focused on the expression levels of the BCL2 gene family and of a panel of B-cell genes associated with venetoclax sensitive MM [ 19 ] in both MMs and pPCLs stratified for the presence of t(11;14).…”

Clinical experiences with venetoclax and other pro-apoptotic agents in lymphoid malignancies: lessons from monotherapy and chemotherapy combination

“…Retrospective “real world” datasets also support the efficacy of venetoclax in t(11;14) positive myeloma, with frequent responses (> 90%) and a median PFS of 10 months among patients with R/R disease in one series [ 127 ]. Responses have also been observed among patients with plasma cell leukemia, in which t(11;14) is frequently detectable, and future studies are required to further evaluate the role of BCL2 inhibition is this high-risk disease [ 127 – 129 ].…”