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

Abstract

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.

Myeloma patients' experiences of haematopoietic stem cell transplant: A qualitative thematic synthesis

“…Moreover, haematology units should examine the possibility of providing exercise equipment in their units (Craike et al, 2013). Evidence-based guidelines on exercise for myeloma patients focus on ensuring that exercise is part of care pathway before and after rehabilitation (Snowden et al, 2017). Further research is needed to examine the role of physical activity in overall wellbeing for myeloma patients during the transplant process and determine its positive effects on levels of fatigue, pain, anxiety, cognitive impairment and depression.…”

Interpreting clinical trial data in multiple myeloma: translating findings to the real-world setting

“…The timing of the patient-reported outcome assessments may also influence the extent to which effects of treatment toxicity are adequately captured, with patient-reported outcomes from clinical studies typically collected over a relatively short follow-up period and at the beginning of a treatment cycle, thus only reflecting patient states with resolved adverse events and/or short-term QoL information 82 . Intra- and inter-trial differential attrition and compliance rates across comparator arms may contribute to data missing not at random that may bias the relative treatment effects.…”

“…Similarly, as noted earlier when discussing patient-reported outcomes, clinical trial data may not necessarily capture the cumulative long-term burden of the disease, its treatment, and the associated comorbidities and toxicity, or the psychosocial effects and lifestyle impact of living with MM 82 . These considerations must be acknowledged in tandem with clinical trial efficacy and safety data when interpreting data on different regimens; in this context, it is also important for patients to be well educated about treatment options and for clinicians to consider patient goals of therapy for what remains a generally incurable disease.…”

PERCEPT myeloma: a protocol for a pilot randomised controlled trial of exercise prehabilitation before and during autologous stem cell transplantation in patients with multiple myeloma

“…There is a need to develop supportive interventions for patients undergoing ASCT aimed at optimising patient fitness before and during ASCT in order to mitigate or minimise the negative effects of treatment on physical and psychological outcomes 11. Prehabilitation and rehabilitation, targeting physical function and fitness, have been suggested as an integral component of myeloma treatment pathways in guidance for managing the consequences of the disease and its treatment; however, further research is required to better understand the potential impact of prehabilitation/rehabilitation before and after treatment for myeloma 12. Given the prevalence of myeloma-related bone destruction in this population, it is also vital to develop and test tailored exercise interventions that are safe and effective at enhancing physical capacity in the presence of disease-related skeletal deformity and pain, common symptoms that limit patients with myeloma being physically active during and after treatment 13…”