<scp>Daratumumab, lenalidomide, and dexamethasone</scp> in systemic <scp>light‐chain</scp> amyloidosis: High efficacy, relevant toxicity and main adverse effect of gain 1q21

Kimmich, Christoph; Terzer, Tobias; Benner, Axel; Hansen, Timon; Carpinteiro, Alexander; Dittrich, Tobias; Veelken, Kaya; Jauch, Anna; Huhn, Stefanie; Basset, Marco; Goldschmidt, Hartmut; Müller‐Tidow, Carsten; Schönland, Stefan; Hegenbart, Ute

doi:10.1002/ajh.26191

Cited by 14 publications

(13 citation statements)

References 7 publications

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“…One patient without haematological response at 6 months from DRd treatment had chromosome 1q21 amplification. A previous publication reporting the efficacy of DRd regimen against relapsed or refractory systemic AL amyloidosis patients, indicated that the existence of 1q21 amplification may reduce the efficacy of DRd 14 . Although the precise mechanisms of low treatment response are unclear, patients with 1q21 amplification may need to consider regimens other than DRd.…”

Section: Characteristic N = 10mentioning

confidence: 99%

Daratumumab, lenalidomide and dexamethasone in newly diagnosed systemic light chain amyloidosis patients associated with multiple myeloma

et al. 2022

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Section: Characteristic N = 10mentioning

confidence: 99%

Daratumumab, lenalidomide and dexamethasone in newly diagnosed systemic light chain amyloidosis patients associated with multiple myeloma

et al. 2022

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“…Probably, due to the low CD38 level, patients with 1q21 gain achieved less satisfactory outcomes than those without this genetic aberration when daratumumab-containing regimens were adopted [ 30 , 66 ]. One study investigating the impact of 1q21 on the standard melphalan/dexamethasone treatment also demonstrates that 1q21 is an independent adverse prognostic factor for survival [ 35 ].…”

Section: Secondary Genetic Eventsmentioning

confidence: 99%

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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“…The main side effects are fluid retention, increase of NT-ProBNP and marked hypotension [27]. However, it is quite effective if used as upfront or relapse treatment in combination with dexamethasone or with alkylating agents [28] or with the monoclonal antibody daratumumab (DRD) [29]. Gain of 1q21 had an adverse impact on treatment results [27,29].…”

Section: Immunomodulatory Agents (Imids)mentioning

confidence: 99%

“…However, it is quite effective if used as upfront or relapse treatment in combination with dexamethasone or with alkylating agents [28] or with the monoclonal antibody daratumumab (DRD) [29]. Gain of 1q21 had an adverse impact on treatment results [27,29]. In DRD treated AL patients calculated median hemEFS and OS were 17.4 and 29.1 months, respectively.…”

Section: Immunomodulatory Agents (Imids)mentioning

confidence: 99%

Treatment in AL Amyloidosis: Moving towards Individualized and Clone-Directed Therapy

Hegenbart

Raab

Schönland

2021

Hemato

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Systemic amyloid light chain (AL) amyloidosis is a rare protein deposition disease caused by a clonal B cell disorder of the bone marrow. The underlying diseases can be plasma cell disorders (monoclonal gammopathy of clinical significance, smoldering or symptomatic myeloma) or B cell non-Hodgkin’s lymphoma (e.g., Waldenstrom’s disease or marginal zone lymphoma) with secretory activity. It is crucial to characterize the underlying disease very precisely as the treatment of AL amyloidosis is directed against the (often small) B cell clone. Finally, the detection of cytogenetic aberrations of the plasma cell clone will likely play an important role for choosing an effective drug in the near future.

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Daratumumab, lenalidomide, and dexamethasone in systemic light‐chain amyloidosis: High efficacy, relevant toxicity and main adverse effect of gain 1q21

Abstract: The genomic landscape of Waldenström macroglobulinemia is characterized by highly recurring MYD88 and WHIM-like CXCR4 mutations, and small somatic deletions associated with B-cell lymphomagenesis.

Cited by 14 publications

References 7 publications

Daratumumab, lenalidomide and dexamethasone in newly diagnosed systemic light chain amyloidosis patients associated with multiple myeloma

Daratumumab, lenalidomide and dexamethasone in newly diagnosed systemic light chain amyloidosis patients associated with multiple myeloma

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

Treatment in AL Amyloidosis: Moving towards Individualized and Clone-Directed Therapy

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