The impact of continuous lenalidomide maintenance treatment on people living with multiple myeloma-a single-centre, qualitative service evaluation study.

PURPOSE: Continuous lenalidomide maintenance treatment after autologous stem cell transplantation delivers improvement in progression free and overall survival among newly diagnosed multiple myeloma patients and has been the standard of care in the UK since March 2021. However, there is scant information about its impact on patients' day-to-day lives. This service evaluation aimed to qualitatively assess patients receiving lenalidomide treatment at a cancer centre in London, in order that the service might better align with needs and expectations of patients. METHODS: We conducted 20 semi-structured interviews among myeloma patients who were on continuous lenalidomide maintenance treatment at a specialist cancer centre in London. Members of the clinical team identified potentially eligible participants to take part, and convenience sampling was used to select 10 male and 10 female patients, median age of 58 (range, 45-71). The median treatment duration was 11 months (range, 1-60 months). Participants were qualitatively interviewed following the same semi-structured interview guide, which was designed to explore patient experience and insights of lenalidomide. Reflexive thematic analysis was used for data analysis. RESULTS: Four overarching themes were as follows: (i) lenalidomide: understanding its role and rationale; (ii) reframing the loss of a treatment-free period to a return to normal life; (iii) the reality of being on lenalidomide: balancing hopes with hurdles; (iv) gratitude and grievances: exploring mixed perceptions of care and communication. Results will be used to enhance clinical services by tailoring communication to better meet patients' preferences when making treatment decisions. CONCLUSION: This study highlights that most patients feel gratitude for being offered continuous lenalidomide and perceive it as alleviating some fears concerning relapse. It reveals variations in side effects in different age groups; younger patients reported no/negligible side effects, whilst several older patients with comorbidities described significant symptom burden, occasionally leading to treatment discontinuation which caused distress at the perceived loss of prolonged remission. Future research should prioritise understanding the unique needs of younger patients living with multiple myeloma.

"What I wanted to do was build myself back up and prepare": qualitative findings from the PERCEPT trial of prehabilitation during autologous stem cell transplantation in myeloma.

BACKGROUND: The addition of qualitative methodology to randomised controlled trials evaluating complex interventions allows better understanding of contextualised factors and their potential influence on trial delivery and outcomes, as well as opportunities for feedback on trial participation to improve future trial protocols. This study explored the experiences of participation in cancer rehabilitation research during active cancer treatment. Participants were people living with haematological cancer myeloma, undergoing autologous stem cell transplantation (ASCT) recruited to the PERCEPT myeloma pilot trial. METHODS: A qualitative semi-structured interview study, embedded within a pilot randomised controlled trial of a physiotherapist-led exercise intervention delivered before, during and after ASCT among people living with myeloma. Transcripts were analysed using reflexive thematic analysis. RESULTS: Interviews from 16 trial participants (n = 8 intervention group; n = 8 control group; mean age 61 years, 56% male) were analysed. Four main themes were identified: (1) "It's not just beneficial for me, it's for people after me as well"; (2) Disparities in experience of recovery - expectations, feeling prepared and support; (3) "What I wanted to do was build myself back up and prepare"; (4) Active ingredients - participants' experience of the trial intervention. Participants reported both altruistic and perceived personal gain as motivators for enrolling in the trial. Disappointment caused by allocation to control arm may have led to participants seeking exercise elsewhere, indicating possible contamination of control condition. Disparities in experience of recovery from transplant were evident with intervention participants reporting greater trajectory of recovery. CONCLUSIONS: The findings from this embedded qualitative study highlight numerous considerations required when designing pilot and efficacy trials of complex interventions. The addition of qualitative investigation offers greater understanding of motivations for participation, intervention mechanisms at play as well as effects of participation that may impact interpretation of quantitative outcomes. TRIAL REGISTRATION: Qualitative findings from a prospectively registered pilot trial (ISRCTN15875290), registered 13/02/2019.

Exercise prehabilitation for people with myeloma undergoing autologous stem cell transplantation: results from PERCEPT pilot randomised controlled trial.

BACKGROUND: Autologous stem cell transplant (ASCT) is first line treatment for newly diagnosed patients with myeloma but often results in functional deficits and reduced quality of life (QOL). Physically active myeloma patients have better QOL, less fatigue and reduced morbidity. This trial aimed to investigate the feasibility of a physiotherapist-led exercise intervention delivered across the continuum of the myeloma ASCT pathway at a UK centre. Initially designed and delivered as a face-to-face trial, the study protocol was adapted to virtual delivery in response to the COVID-19 pandemic. MATERIAL AND METHODS: A pilot randomised controlled trial of a partly supervised exercise intervention with incorporated behaviour change techniques delivered before, during and for 3 months following ASCT compared to usual care. Face-to-face delivery of the pre-ASCT supervised intervention was adapted to virtually-supervised group classes via video conferencing. Primary outcomes related to feasibility; recruitment rate, attrition and adherence. Secondary outcomes included patient reported measures of QOL (EORTC C30, FACT-BMT, EQ5D), and fatigue (FACIT-F), measures of functional capacity (six-minute walk test (6MWT), timed sit-to-stand (TSTS), hand grip strength, self-reported and objective physical activity (PA). RESULTS: Over 11 months 50 participants were enrolled and randomised. Overall, uptake to the study was 46%. The attrition rate was 34%, mainly related to failure to undergo ASCT. Loss of follow-up for other reasons was low. Secondary outcomes demonstrate potential for the benefit of exercise prior to, during and after ASCT with improvements in QOL, fatigue, functional capacity and PA evident on admission for ASCT and 3 months post-ASCT. DISCUSSION: Results indicate acceptability and feasibility of delivering exercise prehabilitation, in person and virtually within the ASCT pathway in myeloma. The effects of prehabilitation and rehabilitation provision as a component of the ASCT pathway warrants further investigation.

High patient satisfaction and increased physical activity following a remote multidisciplinary team multiple myeloma clinic.

PURPOSE: Patients with multiple myeloma suffer from disease-related complications such as bone destruction, toxicities from repeated therapies and age-related co-morbidities. With improved treatment options, patients are living longer and have specific survivorship needs such as low exercise levels that need to be addressed. In this study, we designed, implemented and evaluated a multidisciplinary team (MDT) myeloma clinic that provided participants with tailored exercise and lifestyle advice. METHODS: The Promoting Individualised Self-Management and Survivorship (PrISMS) clinic was set up in two UK myeloma centres. This remote MDT clinic comprised of a doctor, a nurse specialist and a physiotherapist. Patients were required to complete blood tests and a questionnaire about their symptoms and concerns before each consultation. Patient-reported outcome measures were captured using validated questionnaires. Patient feedback was collected using a specially designed survey and structured telephone interviews. RESULTS: Sixty-one patients were enrolled in the pilot clinic with 210 consultations held during the study period. Nine patients had disease progression and were referred safely back to face-to-face clinics. There was a significant improvement in patients' exercise score (p = 0.02) after PrISMS clinic. Patient satisfaction was high, with 83% feeling more confident in self-managing myeloma after PrISMS clinic. CONCLUSION: PrISMS clinic is safe and feasible, with high patient compliant and acceptability. It empowers patients to self-manage their condition and encourages physical activity, which is associated with improved quality of life and fatigue level. Future randomised controlled trials will help to confirm its benefits on patient clinical outcomes and cost-effectiveness.

Myeloma patients' experiences of a supervised physical activity programme: a qualitative study.

PURPOSE: The Myeloma: Advancing Survival Cancer Outcomes Trial (MASCOT) tested the impact of a supervised exercise programme on fatigue, clinical, and patient-reported outcomes in multiple myeloma [MM] patients. The current study explored MM patients' experiences of the programme to guide future interventions. METHODS: Purposive sampling was used to recruit stable MM patients participating in MASCOT. Semi-structured, face-to-face interviews were conducted, transcribed verbatim, and analysed using thematic analysis. RESULTS: Six themes were identified. Key drivers for participation in MASCOT were "Altruism and extended cancer care"; participants wanted to give something back and assist in improving post-treatment care for MM patients, especially as after treatment "Barriers to being physically active" were a fear of damage and lack of health professional guidance. "Influences fostering change within the intervention" included physiotherapy supervision and tailored exercises, which gave participants confidence to push themselves in a safe environment and broke down misconceptions about their body. "Social support", from both family and peers in the programme, promoted motivation and adherence. Participants expressed concerns about "Maintaining things going forward" but had identified mechanisms to aid continuation. "Physical and mental benefits" of the programme were highlighted; participants were able to do things they couldn't before and described feeling free from the constraints of MM. CONCLUSIONS: A post-treatment exercise intervention for MM patients was a positive experience, which enhanced participants' physical and psychological wellbeing. Tailored gym and home-based exercises, a specialist cancer physiotherapist, and sustained support were perceived to be important for success. IMPLICATIONS FOR CANCER SURVIVORS: Exercise support for MM patients, ideally with physiotherapist supervision, should be incorporated into survivorship care to qualitatively improve patients' quality of life, self-efficacy, and mental wellbeing.

Fatigue, quality of life and physical fitness following an exercise intervention in multiple myeloma survivors (MASCOT): an exploratory randomised Phase 2 trial utilising a modified Zelen design.

BACKGROUND: Exercise may improve fatigue in multiple myeloma survivors, but trial evidence is limited, and exercise may be perceived as risky in this older patient group with osteolytic bone destruction. METHODS: In this Phase 2 Zelen trial, multiple myeloma survivors who had completed treatment at least 6 weeks ago, or were on maintenance only, were enrolled in a cohort study and randomly assigned to usual care or a 6-month exercise programme of tailored aerobic and resistance training. Outcome assessors and usual care participants were masked. The primary outcome was the FACIT-F fatigue score with higher scores denoting less fatigue. RESULTS: During 2014-2016, 131 participants were randomised 3:1 to intervention (n = 89) or usual care (n = 42) to allow for patients declining allocation to the exercise arm. There was no difference between groups in fatigue at 3 months (between-group mean difference: 1.6 [95% CI: -1.1-4.3]) or 6 months (0.3 [95% CI: -2.6-3.1]). Muscle strength improved at 3 months (8.4 kg [95% CI: 0.5-16.3]) and 6 months (10.8 kg [95% CI: 1.2-20.5]). Using per-protocol analysis, cardiovascular fitness improved at 3 months (+1.2 ml/kg/min [95% CI: 0.3-3.7]). In participants with clinical fatigue (n = 17), there was a trend towards less fatigue with exercise over 6 months (6.3 [95% CI: -0.6-13.3]). There were no serious adverse events. CONCLUSIONS: Exercise appeared safe and improved muscle strength and cardiovascular fitness, but benefits in fatigue appeared limited to participants with clinical fatigue at baseline. Future studies should focus on patients with clinical fatigue. CLINICAL TRIAL REGISTRATION: The study was registered with ISRCTN (38480455) and is completed.

The views and experiences of people with myeloma referred for autologous stem cell transplantation, who declined to participate in a physiotherapist-led exercise trial: a qualitative study.

BACKGROUND: Recruitment rates to rehabilitation trials are variable among cancer survivors, and deeper investigation into the causes for declining participation is needed. The aim of this study was to qualitatively explore the experiences of people with myeloma referred for autologous stem cell transplant who were approached to take part in a physiotherapist-led exercise trial but declined. METHODS: Participants were asked to participate in this qualitative study after declining to participate in a trial conducted at a UK tertiary cancer center. Semi-structured interviews were conducted. Data was analyzed inductively using reflexive thematic analysis. RESULTS: Interviews from 18 myeloma patients (56% male, mean age 62 years) were analyzed. Four themes were identified: 1) Traveling to the specialist center is challenging, not just logistically; 2) Individualized approach valued but recall of research information variable; 3) Being less active has profound impact yet ameliorative support is lacking; and 4) Common side-effects of treatment are expected and endured but personal impact underestimated and unaddressed. CONCLUSION: A number of barriers to participation were identified. Travel, a commonly cited reason for declining research participation, is more than a logistical issue for cancer survivors experiencing side-effects and the time burden of clinical appointments. Expectation or knowledge of the typical side-effects from myeloma and its treatment may lead to under-reporting of concerns to care providers, despite their impact upon daily activities and quality of life. Approaches used for research recruitment should consider the timing and consequences of ongoing cancer treatment to reduce potential barriers to participation.

Adaptation of the PERCEPT myeloma prehabilitation trial to virtual delivery: changes in response to the COVID-19 pandemic.

INTRODUCTION AND OBJECTIVE: Research activity was impacted by the novel COVID-19 pandemic, the PERCEPT myeloma trial was no exception. This pilot randomised trial delivered a face-to-face exercise intervention prior to and during autologous stem cell transplantation (ASCT) in myeloma patients, as a consequence of COVID-19 it required significant adaptions to continue. This brief communication describes how the previously published study protocol was adapted for virtual delivery. In addition, we highlight the challenge of continuing the study which was embedded within a clinical pathway also impacted by the pandemic. SUMMARY: The original trial protocol was amended and continued to recruit and deliver an exercise prehabilitation intervention virtually. Continued delivery of the intervention was deemed important to participants already enrolled within the trial and the adapted virtual version of the trial was acceptable to the research ethics committee as well as participants. Development of effective, remotely delivered rehabilitation and physical activity programmes are likely to benefit people living with myeloma. The COVID-19 pandemic provided an opportunity to explore the feasibility of a virtual programme for ASCT recipients, however, continued changes to the clinical pathway within which the study was embedded posed the greatest challenge and ultimately led to early termination of recruitment. TRIAL REGISTRATION NUMBER: ISRCTN15875290; pre-results.

Multiple myeloma and physical activity.

OBJECTIVE: Physical activity has been shown to improve quality of life in cancer patients with some evidence in multiple myeloma. This study aimed to determine myeloma patients' exercise levels, their perception of physical activity, and to explore correlations with quality of life. Myeloma outpatients were invited to complete a number of questionnaires, including the Godin leisure-time exercise questionnaire (GLTEQ) to determine their exercise levels, the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire to assess health related quality of life, and the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire to assess fatigue. RESULTS: Of the 65 respondents, 75% would like to increase their exercise level. Weakness, fatigue and pain were the most commonly perceived barriers to physical activity. 59% would like to receive physical activity advice. Only 25% were deemed active based on their GLTEQ scores. Finally, there was a significant positive correlation between the GLTEQ score and the FACT-G score (p < 0.001). Results highlight an unmet exercise need in myeloma patients. Current practice should be reviewed to develop a more holistic care model that incorporates tailored exercise advice or programme.

The adapted Zelen was a feasible design to trial exercise in myeloma survivors.

OBJECTIVES: We used a method rarely seen in cancer behavioral trials to explore methods of overcoming difficulties often seen in randomized controlled trials. We report our experiences of the adapted Zelen design, so that other researchers can consider this approach for behavioral trials. STUDY DESIGN AND SETTING: The adapted Zelen design was used to explore the effects of exercise on multiple myeloma patients fatigue, quality of life, and physical outcomes. All participants consented to an observational cohort study of lifestyle factors but were unaware of subsequent randomization to remain in cohort only group or be offered an exercise intervention requiring second consent. RESULTS: There was lower than expected uptake to the exercise offered group (57%), so the length of recruitment increased from 24 to 29 months to ensure power was reached. At enrollment, patients were unaware of the potential increased commitment, and as a result, 62% of participants allocated to the intervention declined because of the extra time/travel commitment required. This emulates clinical settings and suggests improvements in intervention delivery are required. Our findings suggest that the adapted Zelen design may be useful in limiting dropout of controls due to dissatisfaction from group allocation, or contamination of control arm. CONCLUSION: Future use of this design warrants careful consideration of the study resources and recruitment time frames required but holds potential value in reducing contamination, control group dissatisfaction, and resulting dropout. Adapted Zelen design reduces selection bias and therefore gives clinicians a better understanding of acceptability in clinical settings. Future studies should evaluate control group experiences of the design and formally record contamination throughout the study to confirm its acceptability.

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.

INTRODUCTION: Myeloma, a blood cancer originating from plasma cells, is the most common indication for autologous stem cell transplantation (SCT). Patients with myeloma undergoing autologous SCT (ASCT) experience treatment-related morbidity and reduction in function and well-being for many months post-treatment. Interventions targeting physical functioning delivered prior to and during SCT have shown promising results in mixed haematological populations and may offer a non-pharmacological solution to physically optimising and preparing patients for SCT. The aim of this study is to investigate the feasibility of a physiotherapist-led exercise intervention as an integral part of the myeloma ASCT pathway at a UK tertiary centre. METHODS AND ANALYSIS: PERCEPT is a single-site, pilot randomised controlled trial of an exercise intervention embedded within the myeloma ASCT pathway, compared with usual care. The primary study end points will be feasibility measures of study and intervention delivery including recruitment rates, acceptability of intervention, study completion rate and any adverse events. Secondary end points will evaluate differences between the exercise intervention group and the usual care control group in cancer-related fatigue, quality of life, functional capacity (6 min walk test; handheld dynamometry; a timed sit-to-stand test) and objective and self-reported physical activity. Outcomes will be assessed at four time points, approximately 6-8 weeks prior to SCT, on/around day of SCT, on discharge from SCT hospital admission and 12 weeks post-discharge. The exercise intervention comprises of partly supervised physiotherapist-led aerobic and resistance exercise including behaviour change techniques to promote change in exercise behaviour. The primary outcomes from the trial will be summarised as percentages or mean values with 95% CIs. Group differences for secondary outcomes at each time point will be analysed using appropriate statistical models. ETHICS AND DISSEMINATION: This study has NHS REC approval (Camden and Kings Cross, 19/LO/0204). Results will be disseminated through publication and presentations at haematology and rehabilitation-related meetings. TRIAL REGISTRATION NUMBER: ISRCTN15875290.