Efficacy of lenalidomide as salvage therapy for patients with AL amyloidosis

Kastritis, Efstathios; Gavriatopoulou, Maria; Ρούσσου, Μαρία; Bagratuni, Tina; Migkou, Magdalini; Fotiou, Despina; Ziogas, Dimitrios C.; Kanellias, Nikolaos; Eleutherakis‐Papaiakovou, Evangelos; Dialoupi, Ioanna; Ntanasis‐Stathopoulos, Ioannis; Spyropoulou-Vlachou, Mairylin; Psimenou, Erasmia; Gakiopoulou, Harikleia; Marinaki, Smaragdi; Papadopoulou, Elektra; Ntalianis, Argyrios; Terpos, Evangelos

doi:10.1080/13506129.2018.1540410

Cited by 25 publications

(26 citation statements)

References 32 publications

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“…Full dose lenalidomide can be rarely used in patients with AL amyloidosis. In the current cohort treated with IRd, the overall haematological response rate (65·8%) compared with responses to ixazomib (52–53%) (Sanchorawala et al , ; Dispenzieri et al , ) and 51% (Kastritis et al , ) and 61% (Mahmood et al , ) with lenalidomide. There was suggestion that IRd achieved a deep response (CR/VGPR) in nearly half of all the treated patients (47·4%) compared to just less than a third with lenalidomide + dexamethasone (28%).…”

Section: Discussionmentioning

confidence: 67%

“…Lenalidomide has been linked to renal dysfunction in AL amyloidosis (Specter et al , ) but there are no renal toxicities reported with ixazomib in AL amyloidosis (Sanchorawala et al , ; Dispenzieri et al , ). Kastritis and colleagues did report transient increases (to grade 1) in renal failure and 5·5% developed acute renal failure requiring dialysis (Kastritis et al , ). In this study, 17·5% of patients developed a creatinine increase inclusive of one patient who required dialysis but there was no significant change in the creatinine or eGFR between baseline and six‐month assessments.…”

Section: Discussionmentioning

confidence: 99%

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Use of ixazomib, lenalidomide and dexamethasone in patients with relapsed amyloid light‐chain amyloidosis

et al. 2020

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With improving outcomes in amyloid light-chain (AL) amyloidosis, there is a need to study novel agents in this setting. We report outcomes of 40 patients with relapsed AL amyloidosis treated with ixazomib + lenalidomide + dexamethasone (IRd). Haematological responses were assessed on an intention-to-treat basis at three months: complete response (CR) -8 (20Á5%), very good partial response (VGPR) -8 (20Á5%), partial response (PR) -7 (17Á9%) and no response (NR) -16 (41Á0%). One patient had missing data. Six patients subsequently improved response. Best responses were: CR -10 (25Á6%), VGPR -8 (20Á5%), PR -7 (17Á9%), NR -14 (35Á9%). Cardiac and renal organ responses occurred in 5Á6% and 13Á3% respectively. Median progession-free survival (PFS) was 17Á0 months (95% CI 7Á3-20Á7 months), improving to 28Á8 months (95% CI 20Á6-37Á0 months) in those achieving CR/VGPR. Median overall survival was 29Á1 months (95% CI 24-33 months). Serious adverse events were seen in 14 (35Á0%) patients inclusive of 15 admissions due to: infection (6/15, 40Á0%), fluid overload (5/15, 33Á3%), cardiac arrhythmia (2/15, 13Á3%), renal dysfunction (1/15, 6Á6%) and anaemia (1/15, 6Á6%). In summary, IRd is an oral treatment option with a manageable toxicity profile leading to deep responses in 47% of patients with relapsed AL amyloidosis.

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Section: Discussionmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Use of ixazomib, lenalidomide and dexamethasone in patients with relapsed amyloid light‐chain amyloidosis

et al. 2020

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“…Other agents that have been found to have activity against amyloidosis include immunomodulatory agents such as lenalidomide (Revlimid) and pomalidomide (Pomalyst); however, combinations with these agents yield poorer outcomes for individuals with cardiac involvement ( Kastritis & Dimopoulos, 2015 ; Table 4 ). This may be due to a rise in the NTproBNP previously reported in studies ( Kastritis et al, 2017 ).…”

Section: Treatmentmentioning

confidence: 66%

AL Amyloidosis: Unfolding a Complex Disease

Richards

2019

JADPRO

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“…The lenalidomide-associated toxicities were significant in AL with renal involvement and also in patients with cardiac impairment. Vigorous dose-adjustments were essential to improve tolerability and reduce treatment-induced organ deterioration [23]. The median lenalidomide dosage was 10 mg per day (maximum dose 15 mg per day).…”

Section: Lenalidomidementioning

confidence: 99%

Short tutorial. Treatment options in light chain amyloidosis and monoclonal gammopathy of renal significance

Krauth

Agis

2021

memo

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SummaryAL amyloidosis (AL) and monoclonal gammopathy of renal significance (MGRS) are both paraprotein-associated diseases. Both entities are based on a monoclonal paraprotein produced by a clonal plasma-cell population like in monoclonal gammopathy of undetermined significance (MGUS) or by a B-cell population like in low grade lymphoma. Per definition MGUS and low-grade lymphoma do not require treatment. But in rare cases the monoclonal M‑gradient acts as a “toxic” protein inducing severe multimodal organ damage as in AL and MGRS. Urgent treatment is indicated in AL and in MGRS to avoid irreparable loss of organ function or death. No treatment is currently approved in Europe for AL or MGRS. On January 15, 2021 the US Food and Drug Administration approved the monoclonal anti-CD38 antibody for treatment of AL. To minimize the serum M‑gradient concentration, a clone directed therapy as in multiple myeloma or B‑cell malignancies treatment regimens can be applied. In AL, an additional treatment option is under investigation. These special drugs are directed against the typical amyloid-fibrils responsible for deposition formation. An additional and important consideration in this special field of rare diseases is the option of organ transplantation in particular kidney transplantation in MGRS. All these treatment modalities are addressed in this article.

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Efficacy of lenalidomide as salvage therapy for patients with AL amyloidosis

Cited by 25 publications

References 32 publications

Use of ixazomib, lenalidomide and dexamethasone in patients with relapsed amyloid light‐chain amyloidosis

Use of ixazomib, lenalidomide and dexamethasone in patients with relapsed amyloid light‐chain amyloidosis

AL Amyloidosis: Unfolding a Complex Disease

Short tutorial. Treatment options in light chain amyloidosis and monoclonal gammopathy of renal significance

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