Primary treatment of light-chain amyloidosis with bortezomib, lenalidomide, and dexamethasone

Kastritis, Efstathios; Dialoupi, Ioanna; Gavriatopoulou, Maria; Ρούσσου, Μαρία; Kanellias, Nikolaos; Fotiou, Despina; Ntanasis‐Stathopoulos, Ioannis; Papadopoulou, Elektra; Ziogas, Dimitrios C.; Stamatelopoulos, Kimon; Ntalianis, Argyrios; Eleutherakis‐Papaiakovou, Evangelos; Papanikolaou, Asimina; Migkou, Magdalini; Παπανώτα, Αριστέα-Μαρία; Gakiopoulou, Harikleia; Psimenou, Erasmia; Tselegkidi, Maria Irini; Tsitsilonis, Ourania E.; Kostopoulos, Ioannis V.; Terpos, Evangelos; Dimopoulos, Meletios Α.

doi:10.1182/bloodadvances.2019000147

Cited by 46 publications

(29 citation statements)

References 49 publications

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“…Minimal residual disease (MRD) was assessed by means of next-generation multicolour flow cytometry in patients in CR as previously described. 12,13…”

Section: Methodsmentioning

confidence: 99%

Daratumumab‐based therapy for patients with monoclonal gammopathy of renal significance

et al. 2020

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Treatment of the plasma cell clone in monoclonal gammopathy of renal significance (MGRS) is necessary in order to reduce toxic immunoglobulin load to the kidneys and salvage renal function. There are limited data on the use of daratumumab in patients with MGRS. We summarize our experience with the use of daratumumab-based therapy in 25 MGRS patients, 12 of whom were previously untreated. The median follow-up of the cohort is 14 months. The best overall haematologic response in evaluable patients was complete response (CR) in five (22%), very good partial response (VGPR) in five (22%) and partial response (PR) in seven (30%) patients for an overall response rate of 74%. Two of five patients in CR and two patients with initially detectable clones, but non-measurable immunoglobulins, had undetectable minimal residual disease (MRD) with next-generation flow cytometry (NGF) after therapy. Haematologic response rate for previously untreated patients was 83% vs. 69% for previously treated and for daratumumab combinations it was 91% vs. 64%, and with CR/VGPR 82% vs. 29%, compared to daratumumab monotherapy. At six months, 12/22 (55%) patients not on dialysis achieved a reduction of proteinuria >30%, of at least 0Á5 g/24 h, without an estimated glomerular filtration rate (eGFR) reduction. The toxicity was mild and predictable. In conclusion, daratumumab-based therapy is a new option for patients with MGRS.

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“…Minimal residual disease (MRD) was assessed by means of next-generation multicolour flow cytometry in patients in CR as previously described. 12,13…”

Section: Methodsmentioning

confidence: 99%

Daratumumab‐based therapy for patients with monoclonal gammopathy of renal significance

et al. 2020

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“…The upfront combination of bortezomib and low dose lenalidomide was reported form our group, with hematology response in 89% on intent to treat, including CR in 32% and VGPR in 57%, however, 38% required dose reductions and 27% discontinued lenalidomide due to toxicity. 80 A similar combination with Pomalidomide, bortezomib and dexamethasone was associated with toxicity and early mortality. 81 …”

Section: Treatments That Target Plasma Cellsmentioning

confidence: 99%

Systemic AL Amyloidosis: Current Approaches to Diagnosis and Management

Fotiou

Dimopoulos

2020

HemaSphere

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AL amyloidosis is characterized by a low-level expansion of an indolent, small plasma cell clone that produces amyloidogenic light chains. Amyloid aggregates or preceding intermediaries cause direct cell damage through their proteotoxicity, and amyloid deposits distort tissue architecture, and, eventually, lead to organ impairment. It is a rare, underdiagnosed disease with a diverse clinical presentation depending on the organ tropism of the amyloid fibrils; cardiac and renal involvement is most common, but any organ can be affected, excluding the central nervous system. A high level of awareness and a systematic approach using newly emerging screening biomarkers is required to achieve early diagnosis. Management should be multidisciplinary as supportive management tailored to management of organ dysfunction is paramount to survival and minimization of treatment-associated toxicity. The initial therapeutic aim is to rapidly eliminate the clonal plasma cell that produces the circulating amyloid precursor and achieve a complete hematologic response, and if possible with undetectable minimal residual disease as assessed by next-generation methods (flow and sequencing), with minimal toxicity. Treatment is tailored to the initial risk assessment of the patients. Treatments are based on regimens adapted from the expanding options that are available for multiple myeloma patients and hematological response rates have improved. Organ response rates are strongly associated with deeper hematologic response but usually lag behind hematological response and are also dependent on the initial organ function reserve. Agents directed against the amyloid deposits have been explored to aid amyloid clearance and improve organ function, but data are still negative.

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“…Lenalidomide can also be combined with bortezomib and dexamethasone. This regimen grants a remarkably high hematologic response rate (89%; CR 32%) and, importantly, the response is fast, being achieved after a single cycle in most cases [38].…”

Section: Upfront Conventional Treatmentmentioning

confidence: 99%

Conventional Therapy for Amyloid Light-Chain Amyloidosis

Milani¹,

Palladini²

2020

Acta Haematol

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The vast majority of patients with light-chain (AL) amyloidosis are not eligible for stem cell transplant and are treated with conventional chemotherapy. Conventional regimens are based on various combinations of dexamethasone, alkylating agents, proteasome inhibitors, and immunomodulatory drugs. The choice of these regimens requires a careful risk stratification, based on the extent of amyloid organ involvement, comorbidities, and the characteristics of the amyloidogenic plasma cell clone. Most patients are treated upfront with bortezomib and dexamethasone combined with cyclophosphamide or melphalan. Cyclophosphamide does not compromise stem cell mobilization and harvest and is more manageable in renal failure. Melphalan can overcome the effect of t(11; 14), which is associated with lower response rates and shorter survival in subjects treated with bortezomib and dexamethasone, or in combination with cyclophosphamide. Lenalidomide and pomalidomide are the mainstay of rescue treatment. They are effective in patients exposed to bortezomib, dexamethasone, and alkylators, but deep hematologic responses are rare. Ixazomib, alone or in combination with lenalidomide, increases the rate of complete responses in relapsed/refractory patients. Conventional chemotherapy regimens will represent the backbone for future combinations, particularly with anti-plasma-cell immunotherapy, that will further improve response rates and outcomes.

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Primary treatment of light-chain amyloidosis with bortezomib, lenalidomide, and dexamethasone

Abstract: Key Points Bortezomib with dexamethasone and low-dose lenalidomide is an active therapy for previously untreated patients with AL amyloidosis. VRD can induce MRD-negative responses, but nonhematologic toxicity may be significant in patients with advanced disease.

Cited by 46 publications

References 49 publications

Daratumumab‐based therapy for patients with monoclonal gammopathy of renal significance

Daratumumab‐based therapy for patients with monoclonal gammopathy of renal significance

Systemic AL Amyloidosis: Current Approaches to Diagnosis and Management

Conventional Therapy for Amyloid Light-Chain Amyloidosis

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