Risk of second primary malignancy in patients with AL amyloidosis treated with lenalidomide

Sanchorawala, Vaishali; Shelton, Anthony C; Zeldis, Jerome B.; Seldin, David C.

doi:10.1002/ajh.23470

Cited by 3 publications

(3 citation statements)

References 8 publications

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“…It was, however, striking to note that 55% of evaluable patients achieved a renal response by 18 months (median duration on lenalidomide ‐ 11 months). Interestingly, a cohort of patients treated with long‐term lenalidomide (median duration on lenalidomide ‐ 9 months) also showed an amyloidotic organ response in 44% of evaluable patients (Sanchorawala et al , ). The renal responses in both these series appear to be substantially higher than the previous reports of chemotherapy‐treated patients (55% in the current cohort compared to 25% in long‐term follow‐up of MDex‐treated patients) and appear similar to those reported for patients treated with autologous stem cell transplantation (Cibeira et al , ).…”

Section: Discussionmentioning

confidence: 99%

Lenalidomide and dexamethasone for systemic AL amyloidosis following prior treatment with thalidomide or bortezomib regimens

et al. 2014

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SummaryThe outcomes and responses to treatment remain poorly studied among patients with systemic AL amyloidosis who require further treatment following prior novel agent-based therapy. We report here treatment with lenalidomide-dexamethasone in 84 AL amyloidosis patients with relapsed/refractory clonal disease following prior treatment with thalidomide (76%) and/or bortezomib (68%). On an intention-to-treat (ITT) basis, the overall haematological response rate was 61%, including 20% complete responses. The median overall survival (OS) has not been reached; 2-year OS and progression-free survival (PFS) was 84% and 73%, respectively. Achieving a free light chain (FLC) response was an independent good prognostic factor for OS in multivariate analysis. There was no impact of prior thalidomide or bortezomib therapy on response rate, OS or PFS. 16% achieved an organ response at 6 months, with a marked improvement in organ responses in patients on long term therapy (median duration 11 months) and 55% achieving renal responses by 18 months. Lenalidomide/dexamethasone therapy achieves good haematological responses in patients with AL amyloidosis with relapsed/refractory clonal disease. The rate of renal responses among patients who received prolonged treatment was unexpectedly high, raising the possibility that immunomodulatory effects of lenalidomide therapy might enhance the otherwise slow natural regression of amyloid deposits.

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Section: Discussionmentioning

confidence: 99%

Lenalidomide and dexamethasone for systemic AL amyloidosis following prior treatment with thalidomide or bortezomib regimens

et al. 2014

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“…71 Lenalidomide combined with dexamethasone has been used in a small cohort of patients refractory to alkylators, bortezomib and thalidomide, with a 41% response rate and survival advantage in responders, indicating that IMiDs can have a role in salvage treatment, 72 with no increased incidence of secondary malignancies. 73 Complete response rates remain low with lenalidomidebased regimes and a number of phase II studies have focused on addition of an alkylator to improve the response rates. 24,[38][39][40][41] Studies with additional cyclophosphamide or melphalan report overall hematologic response rates of 55-60% and CRs of approximately 20%.…”

Section: Immunomodulatory Agentsmentioning

confidence: 99%

Update on treatment of light chain amyloidosis

et al. 2014

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Light chain amyloidosis is the most common type of amyloidosis as a consequence of protein misfolding of aggregates composed of amyloid fibrils. The clinical features are dependent on the organs involved, typically cardiac, renal, hepatic, peripheral and autonomic neuropathy and soft tissue. A tissue biopsy or fat aspirate is needed to confirm the presence/type of amyloid and prognostic tools are important in a risk stratified approach to treatment. Autologous stem cell transplant eligibility should be assessed at baseline, weighing the reversible or non-reversible contraindications, toxicity of treatment and chemotherapy alternatives available. Chemotherapy options include melphalan, thalidomide, bortezomib, lenalidomide, bendamustine in combination with dexamethasone. Many studies have explored these treatment modalities, with ongoing debate about the optimal first line and sequential treatment thereafter. Attaining a very good partial response or better is the treatment goal coupled with early assessment central to optimizing treatment. One major challenge remains increasing the awareness of this disease, frequently diagnosed late as the presenting symptoms mimic many other medical conditions. This review focuses on the treatments for light chain amyloidosis, how these treatments have evolved over the years, improved patient risk stratification, toxicities encountered and future directions. ABSTRACT © F e r r a t a S t o r t i F o u n d a t i o n S. Mahmood et al.210 haematologica | 2014; 99(2) rectum or abdominal fat aspirate (the latter being an easy bedside procedure available for all patients including those with hemostatic impairment). 7 Fibril typing is critical in deciding appropriate therapy and performed by immunohistochemistry (widely available but specific only in 75-80% of cases of AL), 8 immunoelectron microscopy (highly specific but limited availability), 9 or lately, mass spectrometry of amyloid deposits obtained by laser capture (rapidly becoming an invaluable adjunct) 10 ( Figure 2). Detecting the underlying clone requires serum and urine electrophoresis and immunofixation, serum free light chain analysis, bone marrow examination and imaging for presence of myeloma-related bone disease.Base-line assessment of organ function (Table 2) is ECG showing small QRS complexes and late gadolinium enhancement of cardiac MRI. The pre-fibrillar light chain aggregates (and possibly the misfolded light chains) can have direct tissue toxicity. Cardiac toxicity of light chains appears to be a significant contributor to myocardial dysfunction seen in AL amyloidosis. This may also be the reason for rapid improvement in NT-proBNP which parallels a hematologic response to therapy often without any evidence of structural cardiac improvement but correlating with clinical improvement in the patients' cardiac symptoms. © F e r r a t a S t o r t i F o u n d a t i o nimportant for prognosis and selection of therapy. Formal testing for autonomic and peripheral neuropathy may be needed in selected cases. 123I labeled s...

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“…Similar programs are also in place for what concerns thalidomide (source http://www.thalomidrems.com/) and pomalidomide (source http://www.pomalystrems.com/). 6 Similar to thalidomide, lenalidomide has been suggested to increase the risk of patients to develop a second primary cancer, 102 , 120 , 124 , 199 yet the underlying molecular mechanisms have not yet been elucidated.…”

Section: Clinical Profile Of Lenalidomidementioning

confidence: 99%

Trial Watch: Lenalidomide-based immunochemotherapy

et al. 2013

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Lenalidomide is a synthetic derivative of thalidomide currently approved by the US Food and Drug Administration for use in patients affected by multiple myeloma (in combination with dexamethasone) and low or intermediate-1 risk myelodysplastic syndromes that harbor 5q cytogenetic abnormalities. For illustrative purposes, the mechanism of action of lenalidomide can be subdivided into a cancer cell-intrinsic, a stromal, and an immunological component. Indeed, lenalidomide not only exerts direct cell cycle-arresting and pro-apoptotic effects on malignant cells, but also interferes with their physical and functional interaction with the tumor microenvironment and mediates a robust, pleiotropic immunostimulatory activity. In particular, lenalidomide has been shown to stimulate the cytotoxic functions of T lymphocytes and natural killer cells, to limit the immunosuppressive impact of regulatory T cells, and to modulate the secretion of a wide range of cytokines, including tumor necrosis factor α, interferon γ as well as interleukin (IL)-6, IL-10, and IL-12. Throughout the last decade, the antineoplastic and immunostimulatory potential of lenalidomide has been investigated in patients affected by a wide variety of hematological and solid malignancies. Here, we discuss the results of these studies and review the status of clinical trials currently assessing the safety and efficacy of this potent immunomodulatory drug in oncological indications.

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Risk of second primary malignancy in patients with AL amyloidosis treated with lenalidomide

Cited by 3 publications

References 8 publications

Lenalidomide and dexamethasone for systemic AL amyloidosis following prior treatment with thalidomide or bortezomib regimens

Lenalidomide and dexamethasone for systemic AL amyloidosis following prior treatment with thalidomide or bortezomib regimens

Update on treatment of light chain amyloidosis

Trial Watch: Lenalidomide-based immunochemotherapy

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