Practical Approaches to the Use of Lenalidomide in Multiple Myeloma: A Canadian Consensus

Reece, Donna; Kouroukis, C. Tom; LeBlanc, Richard; Sébag, Michaël; Song, Kevin; Ashkenas, John

doi:10.1155/2012/621958

Cited by 18 publications

(21 citation statements)

References 64 publications

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“…In conclusion, the IRd safety profile was generally manageable and added limited toxicity to the Rd background regimen. The observed toxicities were familiar for lenalidomide and reported in the literature (http://www.revlimid.com/wp-content/uploads/2013/11/PI.pdf; Dimopoulos et al , ; Reece et al , ; Weber et al , ) and generally consistent with those in studies of single‐agent ixazomib (Kumar et al , 2014b; Richardson et al , ) and IRd (Kumar et al , 2014c; Gupta et al , ). Toxicities were manageable with routine supportive care and dose delays or reductions (Moreau et al , ).…”

Section: Discussionsupporting

confidence: 78%

“…Thrombocytopenia is an overlapping toxicity of ixazomib and lenalidomide (Benboubker et al , ; http://www.revlimid.com/wp-content/uploads/2013/11/PI.pdf. ; Kumar et al , ,c; Lonial et al , ; Reece et al , ; Richardson et al , ). It was reported nearly twice as frequently with IRd versus placebo‐Rd (31% vs. 16%; including 12% vs. 5% grade 3, 7% vs. 4% grade 4), but platelet counts of ≤10 × 10 9 /l and ≤5 × 10 9 /l were infrequently reported (IRd: 2% and <1%; placebo‐Rd: 1% and <1%).…”

Section: Resultsmentioning

confidence: 99%

“…Delayed-onset nausea has been uncommon. Although diarrhoea was reported more frequently with IRd versus placebo-Rd, management should be similar to that in patients receiving Rd (Reece et al, 2012). Prophylactic anti-diarrhoeal medication is not recommended, although anti-diarrhoeal medications (primarily loperamide) and dose modification of lenalidomide or ixazomib should be used as needed.…”

Section: Haematological Toxicitiesmentioning

confidence: 99%

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Management of adverse events associated with ixazomib plus lenalidomide/dexamethasone in relapsed/refractory multiple myeloma

Kumar

Moreau²,

Hari

et al. 2017

Br J Haematol

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SummaryThe oral proteasome inhibitor ixazomib is approved in the United States, European Union and other countries, in combination with oral lenalidomide and dexamethasone (Rd), for the treatment of patients with multiple myeloma who have received at least one prior therapy. Approval was based on the global, randomised, double‐blind, placebo‐controlled Phase III TOURMALINE‐MM1 study of ixazomib‐Rd (IRd) versus placebo‐Rd in patients with relapsed/refractory multiple myeloma. IRd resulted in a significant improvement in progression‐free survival versus placebo‐Rd (median: 20·6 vs. 14·7 months; hazard ratio 0·74). Common toxicities observed more commonly with IRd versus placebo‐Rd were thrombocytopenia, nausea, vomiting, diarrhoea, constipation, rash, peripheral neuropathy, peripheral oedema and back pain; these were generally grade 1/2 in severity except for thrombocytopenia (19% vs. 9% grade 3/4), which appeared manageable and reversible, with no differences between arms in significant bleeding or dose discontinuations. No cumulative toxicities were observed, indicating the potential feasibility of long‐term IRd treatment. Safety data from TOURMALINE‐MM1 are reviewed and guidance for managing clinically relevant adverse events associated with IRd is provided. Most toxicities were manageable with supportive care and dose delays or reductions as needed. Clinicians should be aware of and understand these potential side effects to optimise and prolong patient benefit.

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Section: Discussionsupporting

confidence: 78%

Section: Resultsmentioning

confidence: 99%

Section: Haematological Toxicitiesmentioning

confidence: 99%

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Management of adverse events associated with ixazomib plus lenalidomide/dexamethasone in relapsed/refractory multiple myeloma

Kumar

Moreau²,

Hari

et al. 2017

Br J Haematol

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“…As a result, dose recommendations in patients with MM and RI are in place [97]. Lenalidomide therapy is associated with an increased risk of thromboembolic events [91], and neutropenia and thrombocytopenia are also important side effects [98]. …”

Section: Treatment Of Myelomamentioning

confidence: 99%

Current Trends of Renal Impairment in Multiple Myeloma

2015

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Background: Renal impairment (RI) is a common complication of multiple myeloma (MM). Around 50% of patients with MM have RI at presentation, and up to 5% require dialysis treatment. Severe acute kidney injury (AKI) as a cause of RI is a particular challenge as historically the survival of patients who sustain this complication and require dialysis is very poor. However, in this current period, survival is improving and the focus is on optimum use of novel chemotherapies and the evaluation of extra-corporeal therapies for removal of serum immunoglobulin light chains. Summary: RI in patients with MM is commonly associated with excess monoclonal free light chain (FLC) production; myeloma cast nephropathy is the predominant renal pathology in patients presenting with severe RI secondary to AKI. The majority of patients have mild to moderate RI and recover renal function. However, patients with more severe RI, in particular those with a requirement for dialysis, are less likely to recover renal function. Rapid diagnosis and prompt institution of anti-myeloma therapy is an important determinant of renal function recovery, through targeting early and sustained reduction of involved monoclonal FLC. Novel agents are associated with excellent disease response, and bortezomib is now widely used as a first-line agent in the management of MM in patients with severe RI. Extended haemodialysis using high cut-off dialysers is more effective for extracorporeal removal of FLC than plasma exchange, and clinical trials are in process. High-dose chemotherapy with autologous stem cell transplantation does have a role in patients with severe RI but requires careful patient selection. Key Messages: RI is very common in patients with MM, and renal function recovery is associated with improved clinical outcomes. We summarise the epidemiology of MM in the UK, present the impact of RI and renal function recovery on patient outcome, and describe the current management of MM in western countries. Facts from East and West: (1) A serum creatinine level >2 mg/dl has been reported in 16, 21, 24, and 33% of patients with MM in cohort studies from Japan, Europe, China, and Korea, respectively. A creatinine clearance rate <30 ml/min was observed in 30 and 15% of patients in Chinese and Western MM cohorts, respectively. The commonest cause of severe RI in patients with MM is myeloma cast nephropathy. (2) The efficacy of novel treatments (bortezomib, carfilzomib, thalidomide, and lenalidomide) has predominantly been assessed in Western patients. Bortezomib and dexamethasone are the current standard of care for MM and severe RI in the West. Severe RI is not a contraindication to autologous stem cell transplantation (ASCT). Most of the data are from the West; there are case reports from China describing good outcomes with ASCT. The removal of FLC by high-cut-off hemodialysis is under evaluation in randomized controlled trials (RCTs) in the West. Studies in this area are not yet conducted in China. In China, new treatments, such as bortezomib, are more w...

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“…However, a relatively higher incidence of muscle cramping/spasms was reported in our study (59%) relative to the rate reported for the KRd regimen in patients with relapsed or progressive MM (27–37%; Wang et al , ; Stewart et al , ). Muscle cramps and spasms have been previously associated with the use of lenalidomide and dexamethasone in patients with MM (Reece et al , ; Stewart et al , ) and with the use of vorinostat in patients with cutaneous T‐cell lymphoma (https://www.merck.com/product/usa/pi_circulars/z/zolinza/zolinza_pi.pdf). Notably, in the PANORAMA‐1 study during which patients received a triplet regimen that did not include lenalidomide or vorinostat, the frequency of muscle cramping/spasms was not reported (i.e.…”

Section: Discussionmentioning

confidence: 99%

Phase I study of carfilzomib, lenalidomide, vorinostat, and dexamethasone in patients with relapsed and/or refractory multiple myeloma

et al. 2015

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SummaryResearch has shown that proteasome inhibitors (e.g., carfilzomib), immunomodulatory agents (e.g., lenalidomide), histone deacetylase inhibitors (e.g., vorinostat) and corticosteroids (e.g., dexamethasone) have synergistic anti-multiple myeloma (MM) activity. This phase I dose-escalation study evaluated a regimen combining carfilzomib, lenalidomide, vorinostat and dexamethasone (QUAD) in patients with relapsed and/or refractory MM. Seventeen patients received carfilzomib (15, 20, or , lenalidomide 25 mg, vorinostat 400 mg, and dexamethasone 40 mg. Common grade ≥3 adverse events included neutropenia (53%), thrombocytopenia (53%) and anaemia (41%). The overall response rate was 53%: 12% of patients achieved a very good partial response (PR) and 41% of patients achieved a PR. At a median follow-up of 10 months, median progression-free survival was 12 months and median overall survival was not reached. Treatment with QUAD was feasible and had encouraging activity in patients with relapsed and/or refractory MM.

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Practical Approaches to the Use of Lenalidomide in Multiple Myeloma: A Canadian Consensus

Cited by 18 publications

References 64 publications

Management of adverse events associated with ixazomib plus lenalidomide/dexamethasone in relapsed/refractory multiple myeloma

Management of adverse events associated with ixazomib plus lenalidomide/dexamethasone in relapsed/refractory multiple myeloma

Current Trends of Renal Impairment in Multiple Myeloma

Phase I study of carfilzomib, lenalidomide, vorinostat, and dexamethasone in patients with relapsed and/or refractory multiple myeloma

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