Presence of t(11;14) in AL amyloidosis as a marker of response when treated with a bortezomib-based regimen

Dumas, Brett; Yameen, Hassan; Sarosiek, Shayna; Sloan, J. Mark; Sanchorawala, Vaishali

doi:10.1080/13506129.2020.1778461

Cited by 29 publications

(38 citation statements)

References 21 publications

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“…Bochtler et al first reported in 2015 that t (11;14) was associated with an inferior outcome in patients treated with bortezomib-based regimens in a study with 101 patients [33]. Further study results from other research centers also support Bochtler's finding, indicating that patients with t(11;14) have a lower response rate and shorter median OS time when receiving bortezomib-based regimens as first-line therapy [18,34]. However, these results should still be interpreted with caution since they are retrospective.…”

Section: T(11;14)mentioning

confidence: 81%

Genetic pathogenesis of immunoglobulin light chain amyloidosis: basic characteristics and clinical applications

2021

Exp Hematol Oncol

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Immunoglobulin light chain amyloidosis (AL) is an indolent plasma cell disorder characterized by free immunoglobulin light chain (FLC) misfolding and amyloid fibril deposition. The cytogenetic pattern of AL shows profound similarity with that of other plasma cell disorders but harbors distinct features. AL can be classified into two primary subtypes: non-hyperdiploidy and hyperdiploidy. Non-hyperdiploidy usually involves immunoglobulin heavy chain translocations, and t(11;14) is the hallmark of this disease. T(11;14) is associated with low plasma cell count but high FLC level and displays distinct response outcomes to different treatment modalities. Hyperdiploidy is associated with plasmacytosis and subclone formation, and it generally confers a neutral or inferior prognostic outcome. Other chromosome abnormalities and driver gene mutations are considered as secondary cytogenetic aberrations that occur during disease evolution. These genetic aberrations contribute to the proliferation of plasma cells, which secrete excess FLC for amyloid deposition. Other genetic factors, such as specific usage of immunoglobulin light chain germline genes and light chain somatic mutations, also play an essential role in amyloid fibril deposition in AL. This paper will propose a framework of AL classification based on genetic aberrations and discuss the amyloid formation of AL from a genetic aspect.

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Section: T(11;14)mentioning

confidence: 81%

Genetic pathogenesis of immunoglobulin light chain amyloidosis: basic characteristics and clinical applications

2021

Exp Hematol Oncol

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“…But referring to the studies in MM, the potential mechanisms have been suggested as follows: proteasome mutations, such as proteasome β5 subunit (PSMB5); key stress signal pathway cross-talk, such as HSP family members; and bone marrow microenvironment changes, such as overexpression of IGF-1 (17). Interestingly, in light-chain amyloidosis, another aberrant light-chain gammopathy, the presence of t (11;14) is a marker of poor response to a bortezomib-based regimen (18,19). We did not conduct a gene test or FISH test on bone marrow, so the resistance mechanism of our two patients remained undetermined.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Lenalidomide as a Second-Line Treatment for Bortezomib-Ineffective Nephrotic Syndrome Caused by LCDD: 2 Case Reports and a Literature Review

Zhang

Zhou

et al. 2021

Front. Med.

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Background: Light-chain deposition disease (LCDD) is a rare systemic disorder characterized by the deposition of monoclonal light chains in organs. The kidney is a prominent target of light-chain deposition, with a median time to end-stage renal disease (ESRD) of 2.7 years and 5-year ESRD-free survival of 37%. The therapeutic management of LCDD remains ill-defined. In addition to bortezomib-based therapy as first-line therapy, the effect of lenalidomide on LCDD is rarely reported.Case Presentation: This study describes two male LCDD patients in their 60s with nephrotic syndrome and moderately impaired renal function. One patient had monoclonal IgGλ with underlying MGRS, and another had monoclonal IgGκ with underlying monoclonal gammopathy that developed into symptomatic MM during follow-up. The hallmarks of this disease were consistent with previous reports. Both patients initially received BCD therapy, but no hematological response was observed. Consequently, the nephrotic syndrome was refractory. Sequential Rd therapy was initiated, and partial hematological response and nephrotic remission were observed in the IgGλ patient but absent in the IgGκ patient.Conclusion: Limited reports have demonstrated the effect of lenalidomide in LCDD. We report the outcome of lenalidomide in two cases of bortezomib-resistant LCDD. This treatment might be a beneficial supplement for those unresponsive or intolerant to bortezomib in LCDD, but the effect should be prospectively investigated.

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“…The large structural chromosomal translocation t(11;14) is found to be over-represented in the plasma cell neoplasm underlying AL compared to multiple myeloma, with a prevalence of ~40-50%. (52,53) Both historical series and subgroup analysis from the ANDROMEDA study confirm, inferior rates of deep hematologic responses in t(11;14) patients treated with bortezomib based regimens in the absence of daratumumab. (54) In the ANDROMEDA study ~40% of patients in each arm had t (11;14).…”

Section: What May Change In the Future?mentioning

confidence: 91%

How I Manage Systemic Light Chain Amyloidosis

Kaufman

Cerchione

2021

Hematology Reports

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Light chain amyloidosis (AL) is a protein deposition disorder with a heterogenous pattern of organ involvement and dysfunction that varies by affected patient. Often diagnosed late after the onset of symptoms, appropriate and correct diagnosis, and prompt initial management, typically with anti-plasma cell therapy targeting the underlying cell producing the aberrant light chain protein, can lead to significant improvement in patient symptoms, organ function and lifespan. With recent publication of phase III studies focused on AL, and a changing regulatory landscape providing greater availability of novel therapies, the management of AL is in some ways more complex with greater options to consider. In this clinical review, a discussion of the diagnosis, staging, and goals of therapy transitions to a focus on contemporary management questions to outline our clinical approach to multi-disciplinary management and long term follow up for patients with suspected or confirmed AL.

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Presence of t(11;14) in AL amyloidosis as a marker of response when treated with a bortezomib-based regimen

Cited by 29 publications

References 21 publications

Genetic pathogenesis of immunoglobulin light chain amyloidosis: basic characteristics and clinical applications

Genetic pathogenesis of immunoglobulin light chain amyloidosis: basic characteristics and clinical applications

Case Report: Lenalidomide as a Second-Line Treatment for Bortezomib-Ineffective Nephrotic Syndrome Caused by LCDD: 2 Case Reports and a Literature Review

How I Manage Systemic Light Chain Amyloidosis

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