Lenalidomide-induced diarrhea in patients with myeloma is caused by bile acid malabsorption that responds to treatment

Pawlyn, Charlotte; Khan, Mohid S.; Muls, Ann; Sriskandarajah, Priya; Kaiser, Martin; Davies, Faith E.; Morgan, Gareth J.; Andreyev, H. J. N.

doi:10.1182/blood-2014-06-583302

Cited by 62 publications

(42 citation statements)

References 10 publications

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“…Longterm lenalidomide therapy may be associated with chronic diarrhea. 22 Side effects observed with MPR and MPR followed by R maintenance in the MM015 trial 23 are similar to those reported for the FIRST trial and are listed in Table S2A. Lenalidomide therapy is associated with an increased risk for second primary malignancies, especially in the post-transplantation setting, [24][25][26] or after a melphalan-containing regimen, 27 and after an IMiD-based induction therapy.…”

supporting

confidence: 62%

“…Increased accumulation of bile acids in the small bowel may lead to debilitating episodes of diarrhea that may severely impair the patients' quality of life. 22 The diagnosis can be established by non-invasive selenium homocholic acid taurine (SeHCAT) scanning or is supported when treatment with bile acid binders such as colesevelam results in improvement of symptoms. 75 Following the diagnosis, dietary fat intake should be reduced (to 20% of total calories) and/or colesevelam prescribed.…”

Section: Diarrheamentioning

confidence: 99%

See 1 more Smart Citation

Prevention and management of adverse events of Novel agents in multiple myeloma: A consensus of the european myeloma network

Ludwig

Delforge²,

Facon

et al. 2017

Leukemia

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During the last few years, several new drugs have been introduced for treatment of patients with multiple myeloma, which have significantly improved treatment outcome. All of these novel substances differ at least in part in their mode of action from similar drugs of the same drug class, or are representatives of new drugs classes, and as such present with very specific side effect profiles. In this review, we summarize these adverse events, provide information on their prevention, and give practical guidance for monitoring of patients and for management of adverse events.

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supporting

confidence: 62%

Section: Diarrheamentioning

confidence: 99%

Prevention and management of adverse events of Novel agents in multiple myeloma: A consensus of the european myeloma network

Ludwig

Delforge²,

Facon

et al. 2017

Leukemia

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“…Bowel disturbance, particularly diarrhoea, is a common and sometimes persistent side effect of treatment with novel agents, such as bortezomib, and histone deacetylase inhibitors, such as panobinostat. Diarrhoea also occurs with lenalidomide; it is probably due to bile acid malabsorption and responds to bile acid sequestrants (Pawlyn et al , ). Patients with persistent diarrhoea with no obvious infectious aetiology need referral to a gastroenterologist to exclude malignancy, underlying bowel disease, AL amyloidosis and bile acid malabsorption.…”

Section: Part 1 Long‐term Physical Consequencesmentioning

confidence: 99%

Guidelines for screening and management of late and long‐term consequences of myeloma and its treatment

et al. 2017

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SummaryA growing population of long-term survivors of myeloma is now accumulating the 'late effects' not only of myeloma itself, but also of several lines of treatment given throughout the course of the disease. It is thus important to recognise the cumulative burden of the disease and treatment-related toxicity in both the stable and active phases of myeloma, some of which is unlikely to be detected by routine monitoring. We summarise here the evidence for the key late effects in long-term survivors of myeloma, including physical and psychosocial consequences (in Parts 1 and 2 respectively), and recommend the use of late-effects screening protocols in detection and intervention. The early recognition of late effects and effective management strategies should lead to an improvement in the management of myeloma patients, although evidence in this area is currently limited and further research is warranted.Keywords: myeloma, late effects, quality of life, haematopoietic stem cell transplantation, chemotherapy. MethodologyThese guidelines were developed using the following stages:• Review of key literature from 1 April 2006 to 31 March 2016 using the Cochrane database (search term: myeloma) and Medline: search terms used were [myeloma] + late effects, long term effects, frailty, geriatric assessment, infection, infection prophylaxis, vaccination, nutrition, exercise, rehabilitation, employment, endocrine, disability, late treatment consequences, cancer survivorship (for all papers); and psychological, fatigue, second primary malignancy, quality of life, infection (reviews). As organ-specific areas, such as renal and bone, have been covered in previous guidelines, searches were not re-performed.• Development of key recommendations based on randomised, controlled trial evidence. In the absence of randomised data, recommendations were developed on the basis of literature review and a consensus of expert opinion.• Updating of the levels of evidence and grades of recommendation using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) nomenclature for assessing the quality of evidence and providing strength of recommendations (Appendix; http:// www.gradeworkinggroup.org/index.htm).• Review of the manuscript was performed by the British Society for Haematology (BSH) Guidelines Committee and Haemato-Oncology Task Force, and the BSH sounding board, comprised of 50 or more members of the BSH who have reviewed this Guidance and commented on its content and applicability in the UK setting, consistent with the primary target audience of UK-based multidisciplinary clinical teams treating myeloma and its complications. Involvement of patient perspectives was through Myeloma UK.• In preparing these guidelines, the authors have considered overall cost-effectiveness and budget impact of recommended interventions as well as clinical efficacy data and the burden/impact on patients. Formal health economic assessments have not been carried out.

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“…Lenalidomide-induced diarrhea is often due to bile acid malabsorption and can be effectively treated with bile acid sequestrants such as cholestyramine and colesevelam. 52 Patients who are experiencing an indolent relapse of the myeloma while taking maintenance lenalidomide may respond when the dose is increased or the drug is combined with other agents such as bortezomib or cyclophosphamide.…”

Section: Drugs Approved For Therapy For Multiple Myelomamentioning

confidence: 99%

Therapy for Relapsed Multiple Myeloma

Dingli

Ailawadhi

Bergsagel

et al. 2017

Mayo Clinic Proceedings

123

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Life expectancy in patients with multiple myeloma is increasing because of the availability of an increasing number of novel agents with various mechanisms of action against the disease. However, the disease remains incurable in most patients because of the emergence of resistant clones, leading to repeated relapses of the disease. In 2015, 5 novel agents were approved for therapy for relapsed multiple myeloma. This surfeit of novel agents renders management of relapsed multiple myeloma more complex because of the occurrence of multiple relapses, the risk of cumulative and emergent toxicity from previous therapies, as well as evolution of the disease during therapy. A group of physicians at Mayo Clinic with expertise in the care of patients with multiple myeloma regularly evaluates the evolving literature on the biology and therapy for multiple myeloma and issues guidelines on the optimal care of patients with this disease. In this article, the latest recommendations on the diagnostic evaluation of relapsed multiple myeloma and decision trees on how to treat patients at various stages of their relapse (off study) are provided together with the evidence to support them.

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Lenalidomide-induced diarrhea in patients with myeloma is caused by bile acid malabsorption that responds to treatment

Cited by 62 publications

References 10 publications

Prevention and management of adverse events of Novel agents in multiple myeloma: A consensus of the european myeloma network

Prevention and management of adverse events of Novel agents in multiple myeloma: A consensus of the european myeloma network

Guidelines for screening and management of late and long‐term consequences of myeloma and its treatment

Therapy for Relapsed Multiple Myeloma

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