Prognostic impact of t(11;14) in multiple myeloma: Black and white or shades of gray?

Chakraborty, Rajshekhar; Lentzsch, Suzanne

doi:10.1002/cncr.33206

Cited by 4 publications

(5 citation statements)

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“…Patients with this specific translocation have a unique myeloma type and are less likely to be hyperdiploid ( 17 ). They show a two-fold increased incidence of light-chain or non-secretory myeloma, are more likely to present with bone disease, and harbor uncommon heavy-chain isotypes such as immunoglobulin M (IgM) or IgE ( 10 , 39 – 42 ). Malignant PCs are less mature with scant cytoplasm, have a lymphoplasmacytic phenotype with CD20 expression in roughly half of the cases and, most critically, are prone to apoptosis through the anti-apoptotic protein BCL2, which is the target for venetoclax ( 39 , 40 , 43 ).…”

Section: Translocation T(11:14) In Mm: Update On Molecular and Clinic...mentioning

confidence: 99%

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Exploring the current molecular landscape and management of multiple myeloma patients with the t(11;14) translocation

2022

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Multiple myeloma (MM) is a genetically complex disease. The key myeloma-initiating genetic events are hyperdiploidy and translocations involving the immunoglobulin heavy chain (IgH) enhancer on chromosome 14, which leads to the activation of oncogenes (e.g., CCND1, CCND3, MAF, and MMSET). The t(11;14) translocation is the most common in MM (15%–20%) and results in cyclin D1 (CCND1) upregulation, which leads to kinase activation and tumor cell proliferation. Notably, t(11;14) occurs at a higher rate in patients with plasma cell leukemia (40%) and light chain amyloidosis (50%). Patients with myeloma who harbor the t(11;14) translocation have high levels of the anti-apoptotic protein B-cell lymphoma 2 (BCL2). Multiple studies demonstrated that the presence of t(11;14) was predictive of BCL2 dependency, suggesting that BCL2 could be a target in this subtype of myeloma. Venetoclax, an oral BCL2 inhibitor, has shown remarkable activity in treating relapsed/refractory MM patients with t(11;14) and BCL2 overexpression, either as monotherapy or in combination with other anti-myeloma agents. In this review, we describe the molecular defects associated with the t(11;14), bring into question the standard cytogenetic risk of myeloma patients harboring t(11;14), summarize current efficacy and safety data of targeted venetoclax-based therapies, and discuss the future of individualized or precision medicine for this unique myeloma subgroup, which will guide optimal treatment.

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Section: Translocation T(11:14) In Mm: Update On Molecular and Clinic...mentioning

confidence: 99%

“…African Americans or individuals with a high degree of African ancestry have an increased prevalence of the t(11;14) translocation (36,37). This finding may partially explain the influence of race on prognosis and outcomes in MM, a complex subject with conflicting results under investigation (38,39).…”

Section: Introductionmentioning

confidence: 99%

Exploring the current molecular landscape and management of multiple myeloma patients with the t(11;14) translocation

2022

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“…Some studies showed that patients with t(11;14) should be considered as standard-risk ( 4 , 7 , 17 ), while other argued that t(11;14) was a negative indicator associated with inferior survival to other standard-risk patients, especially in novel agent era ( 6 , 18 , 19 ). In general, t(11;14) was recognized as a group of heterogeneous disease, which had shown huge discrepancies in outcomes ( 11 , 20 , 21 ). Herein we obtained credible data from 211 newly diagnosed MM patients with t(11;14) and analyzed whether CD20 expression detected by flow cytometry could further separate the different prognosis outcomes of t(11;14).…”

Section: Discussionmentioning

confidence: 99%

“…( 12 ) also reported a slow onset of response while comparable best response and longer survival of CD20 positive MM patients. Considering the fact that patients with t(11;14) usually exhibited a decreased proliferative index and a lower deep response rate ( 20 , 30 ), it could be speculated that CD20 positive t(11;14) myeloma referred to a more indolent clinical course with a better outcome.…”

Section: Discussionmentioning

confidence: 99%

CD20 expression: A risk stratification factor for newly diagnosed multiple myeloma with t(11;14)

et al. 2022

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ObjectiveTranslocation (11;14) is one of the most frequent recurrent cytogenetic abnormalities in multiple myeloma (MM), while its clinical prognostic value remains controversial. CD20 expression is uncommon in MM while strongly associated with t(11;14). This study aimed to investigate whether CD20 could provide further prognostic value in MM patients harboring t(11;14).MethodsCD20 expression detected by flow cytometry was retrospectively analyzed in 211 newly diagnosed MM patients with t(11;14). The clinical characteristics and outcomes were analyzed between CD20 positive and negative patients.ResultsCD20 expression was found in 34.6% (73/211) newly diagnosed MM (NDMM) patients with t(11;14), associated with lower serum creatine levels and lower incidence of plasmacytoma. Based on similar treatment regimens, CD20 positive patients had a comparable overall response rate to CD20 negative patients, whereas had a lower CR/sCR (complete response/stringent complete response) rate than the latter (31.4% vs. 46.4%, P =0.045). Nevertheless, CD20 positive patients had a longer tendency of progression-free survival (PFS) (59.0 vs. 29.0 months, P =0.163) and significantly longer overall survival (OS) (99.0 vs. 56.0 months, P=0.003) than CD20 negative patients. Further investigation among CD20 expression proportion showed that strong expression of CD20 (>80% of bone marrow plasma cells) exhibited the longest OS (median not reached, P =0.011). However, the favorable impact of CD20 expression on survival was eliminated with the contaminant presence of cytogenetic abnormalities besides t(11;14). Autologous stem cell transplantation (ASCT) could improve the prognosis of CD20 negative t(11;14) patients. Multivariate analysis confirmed that CD20 expression was an independent favorable indicator for longer OS in t(11;14) MM patients.ConclusionCD20 expression is a favorable prognostic factor in NDMM with t(11;14) and could provide further risk-stratification value in this heterogeneous disease subgroup.

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“…The results indicated that t(11;14) behaved rather like an "intermediate-risk" disease, since all outcomes were inferior compared to the patients with no translocation and superior to those with non-t (11;14). The impaired effectiveness of PIs in inducing endoplasmic reticulum stress [24] and the negative impact of bortezomib-based therapy regimens in t(11;14) light-chain amyloidosis could be responsible for the inferior response rates in these special patient cohorts [41,42].…”

Section: Dynamic Role Of T(11;14) In Shaping the MM Prognosis Landsca...mentioning

confidence: 99%

The Role of t(11;14) in Tailoring Treatment Decisions in Multiple Myeloma

Kleber,

Ntanasis-Stathopoulos,

Terpos

2023

Cancers

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Multiple myeloma (MM) represents a hematological neoplasia with an uncontrolled proliferation of malignant plasma cells and complex cytogenetic abnormalities. t(11;14) has emerged as a crucial genetic aberration and is one of the most common primary translocations in MM. Patients harboring t(11;14) represent a distinctive subgroup with a clinical profile that differs from t(11;14)-negative MM risk categories. One of the key features linked with t(11;14) is the BCL2 dependency, indicating vulnerability to BCL2 inhibition. BCL2 inhibitors, such as venetoclax, demonstrated impressive efficacy alone or in combination with other anti-myeloma drugs in patients with RRMM accompanied by t(11;14) and BCL2 overexpression. Therefore, t(11;14) plays a key role in both risk stratification and informed decision making towards a tailored therapy. In this review, we highlight the biology of t(11;14) in MM cells, summarize the current evolving role of t(11;14) in the era of novel agents and novel targeted therapies, illuminate current efficacy and safety data of BCL2-based treatment options and explore the future prospects of individualized precision medicine for this special subgroup of patients with MM.

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Prognostic impact of t(11;14) in multiple myeloma: Black and white or shades of gray?

Cited by 4 publications

References 21 publications

Exploring the current molecular landscape and management of multiple myeloma patients with the t(11;14) translocation

Exploring the current molecular landscape and management of multiple myeloma patients with the t(11;14) translocation

CD20 expression: A risk stratification factor for newly diagnosed multiple myeloma with t(11;14)

The Role of t(11;14) in Tailoring Treatment Decisions in Multiple Myeloma

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