RESUMEN
Multiple myeloma is the second most common haematological malignancy in high-income countries, and typically starts as asymptomatic precursor conditions-either monoclonal gammopathy of undetermined significance or smouldering multiple myeloma-in which initiating genetic abnormalities, such as hyperdiploidy and translocations involving the immunoglobulin heavy chain, are already present. The introduction of immunomodulatory drugs, proteasome inhibitors, and CD38-targeting antibodies has extended survival, but ultimately the majority of patients will die from their disease, and some from treatment-related complications. Disease progression and subsequent relapses are characterised by subclonal evolution and increasingly resistant disease. Patients with multiple myeloma usually have hypercalcaemia, renal failure, anaemia, or osteolytic bone lesions-and a detailed diagnostic investigation is needed to differentiate between symptomatic multiple myeloma that requires treatment, and precursor states. Risk stratification using both patient-specific (eg, performance status) and disease-specific (eg, presence of high-risk cytogenetic abnormalities) is important for prognosis and to define the best treatment strategy. Current research strategies include the use of minimal residual disease assays to guide therapy, refining immunotherapeutic approaches, and intercepting disease early in smouldering multiple myeloma.
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Mieloma Múltiple , Progresión de la Enfermedad , Humanos , Gammopatía Monoclonal de Relevancia Indeterminada/tratamiento farmacológico , Gammopatía Monoclonal de Relevancia Indeterminada/genética , Gammopatía Monoclonal de Relevancia Indeterminada/patología , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/genética , Mieloma Múltiple/patología , Factores de RiesgoRESUMEN
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.
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Mieloma Múltiple , Ejercicio Físico , Terapia por Ejercicio , Humanos , Mieloma Múltiple/terapia , Investigación Cualitativa , Calidad de VidaRESUMEN
The proteasome inhibitors, carfilzomib and bortezomib, are widely used to treat myeloma but head-to-head comparisons have produced conflicting results. We compared the activity of these proteasome inhibitors in combination with cyclophosphamide and dexamethasone (KCd vs. VCd) in second-line treatment using fixed duration therapy and evaluated the efficacy of carfilzomib maintenance. MUKfive was a phase II controlled, parallel group trial that randomized patients (2:1) to KCd (n=201) or VCd (n=99); responding patients on carfilzomib were randomized to maintenance carfilzomib (n=69) or no further treatment (n=72). Primary endpoints were: (i) very good partial response (non-inferiority, odds ratio [OR] 0.8) at 24 weeks, and (ii) progression-free survival. More participants achieved a very good partial response or better with carfilzomib than with bortezomib (40.2% vs. 31.9%, OR=1.48, 90% confidence interval [CI]: 0.95, 2.31; non-inferior), with a trend for particular benefit in patients with adverse-risk disease. KCd was associated with higher overall response (partial response or better, 84.0% vs. 68.1%, OR=2.72, 90% CI: 1.62, 4.55, P=0.001). Neuropathy (grade ≥3 or ≥2 with pain) was more common with bortezomib (19.8% vs. 1.5%, P<0.0001), while grade ≥3 cardiac events and hypertension were only reported in the KCd arm (3.6% each). The median progression-free survival in the KCd arm was 11.7 months vs. 10.2 months in the VCd arm (hazard ratio [HR]=0.95, 80% CI: 0.77, 1.18). Carfilzomib maintenance was associated with longer progression-free survival, median 11.9 months vs. 5.6 months for no maintenance (HR 0.59, 80% CI: 0.46-0.77, P=0.0086). When used as fixed duration therapy in first relapase, KCd is at least as effective as VCd, and carfilzomib is an effective maintenance agent. This trial was registered with International Standard Randomised Controlled Trial Number (ISRCTN) identifier: ISRCTN17354232.
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Mieloma Múltiple , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bortezomib/uso terapéutico , Ciclofosfamida/efectos adversos , Dexametasona/uso terapéutico , Humanos , Mieloma Múltiple/tratamiento farmacológico , OligopéptidosRESUMEN
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.
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Terapia por Ejercicio/métodos , Mieloma Múltiple/terapia , Aptitud Física/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Supervivientes de Cáncer , Estudios de Cohortes , Terapia por Ejercicio/efectos adversos , Fatiga/etiología , Fatiga/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/complicaciones , Mieloma Múltiple/fisiopatología , Calidad de Vida , SobrevivientesRESUMEN
Haematology patients receiving chemo- or immunotherapy are considered to be at greater risk of COVID-19-related morbidity and mortality. We aimed to identify risk factors for COVID-19 severity and assess outcomes in patients where COVID-19 complicated the treatment of their haematological disorder. A retrospective cohort study was conducted in 55 patients with haematological disorders and COVID-19, including 52 with malignancy, two with bone marrow failure and one immune-mediated thrombotic thrombocytopenic purpura (TTP). COVID-19 diagnosis coincided with a new diagnosis of a haematological malignancy in four patients. Among patients, 82% were on systemic anti-cancer therapy (SACT) at the time of COVID-19 diagnosis. Of hospitalised patients, 37% (19/51) died while all four outpatients recovered. Risk factors for severe disease or mortality were similar to those in other published cohorts. Raised C-reactive protein at diagnosis predicted an aggressive clinical course. The majority of patients recovered from COVID-19, despite receiving recent SACT. This suggests that SACT, where urgent, should be administered despite intercurrent COVID-19 infection, which should be managed according to standard pathways. Delay or modification of therapy should be considered on an individual basis. Long-term follow-up studies in larger patient cohorts are required to assess the efficacy of treatment strategies employed during the pandemic.
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Antineoplásicos/uso terapéutico , COVID-19/complicaciones , Enfermedades Hematológicas/complicaciones , Inmunoterapia , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Población Negra , COVID-19/mortalidad , COVID-19/terapia , Comorbilidad , Infección Hospitalaria/complicaciones , Femenino , Enfermedades Hematológicas/tratamiento farmacológico , Enfermedades Hematológicas/mortalidad , Enfermedades Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas , Humanos , Leucemia/complicaciones , Leucemia/tratamiento farmacológico , Leucemia/mortalidad , Londres/epidemiología , Linfoma/complicaciones , Linfoma/tratamiento farmacológico , Linfoma/mortalidad , Masculino , Persona de Mediana Edad , Respiración Artificial , Estudios Retrospectivos , Factores de Riesgo , SARS-CoV-2 , Trombofilia/tratamiento farmacológico , Trombofilia/etiología , Resultado del Tratamiento , Adulto JovenAsunto(s)
Bortezomib/uso terapéutico , Dexametasona/uso terapéutico , Doxorrubicina/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Adulto , Anciano , Bortezomib/farmacología , Dexametasona/farmacología , Doxorrubicina/farmacología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Resultado del TratamientoAsunto(s)
Vacuna BNT162/administración & dosificación , COVID-19/inmunología , ChAdOx1 nCoV-19/administración & dosificación , Gammopatía Monoclonal de Relevancia Indeterminada/inmunología , SARS-CoV-2/inmunología , Mieloma Múltiple Quiescente/inmunología , Vacunación , Anciano , Anticuerpos Antivirales , Vacuna BNT162/inmunología , COVID-19/prevención & control , ChAdOx1 nCoV-19/inmunología , Femenino , Humanos , MasculinoRESUMEN
Myeloma bone disease results from an uncoupling of osteoclastic resorption and osteoblastic bone formation, but early changes in osteogenic function remain poorly defined. We used the KMS12BM xenograft model to investigate cellular and molecular events at early and late stages of disease. Lytic lesions and changes in osteoblast and osteoclast numbers occur late (8 weeks), however, micro-computed tomography of femora revealed significant reduction in bone volume at earlier disease stages (3 weeks) when tumour burden is low. Calcein labelling demonstrated reduced mineralization and bone formation at 3 weeks, suggesting functional impairment despite preserved osteoblast numbers. Osteo-progenitors from compact bone increased early (1 week), but fell at 3 weeks and were profoundly suppressed by 8 weeks. Exposure of osteoblast progenitors to multiple myeloma (MM) cells in vitro induced cell cycling, suggesting a mechanistic basis for early expansion of osteo-progenitors. We observed temporal changes in chemokine, osteogenic and osteoclastogenic genes in the stromal compartment. Notably, an early rise in CCL3 may underlie functional changes in mature osteoblasts at 3 weeks. Our data indicate that MM has distinct effects on mature osteoblasts and immature osteo-progenitors. Our findings argue for early clinical intervention to prevent bone changes that ultimately lead to the development of osteolytic disease.
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Mieloma Múltiple/patología , Osteoblastos/fisiología , Osteogénesis/fisiología , Células Madre/patología , Animales , Resorción Ósea/fisiopatología , Ciclo Celular/fisiología , Técnicas de Cocultivo , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Femenino , Regulación de la Expresión Génica/fisiología , Xenoinjertos , Humanos , Ratones Endogámicos NOD , Ratones SCID , Mieloma Múltiple/fisiopatología , Trasplante de Neoplasias , Osteoclastos/patología , Células del Estroma/metabolismo , Ensayo de Tumor de Célula Madre , Microtomografía por Rayos XRESUMEN
B-cell maturation antigen (BCMA, also termed TNFRSF17) is an attractive therapeutic target due to its restricted expression on normal and malignant plasma cells (PC). GSK2857916 (or J6M0-MMAF) is a BCMA-specific antibody conjugated to the microtubule-disrupting agent monomethyl auristatin F (MMAF) via a protease-resistant linker. To evaluate the clinical potential of this agent, tumour cells from seventy multiple myeloma (MM) patients were assessed for BCMA expression by immunohistochemistry and flow cytometry. All patients tested expressed BCMA, at varying levels, and both surface and intracellular expression were observed. BCMA expression is maintained through relapse, extramedullary spread and in residual disease post therapy. BCMA levels may also be prognostically useful as higher levels of BCMA were associated with poorer outcomes, even taking into account genetic risk. We observed rapid internalization of surface BCMA and newly expressed protein by 1 h, suggesting a mechanism for J6M0-MMAF activity even with low surface antigen. J6M0-MMAF mediated cytotoxicity of MM cells varied with dose and antigen levels, with clonogenic progenitors killed at lower doses than mature cells. In comparison, J6M0-MMAF killing of primary CD138(+) myeloma cells occurred with slower kinetics. Our observations support BCMA to be a promising therapeutic target in MM for novel therapies such as J6M0-MMAF.
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Antígeno de Maduración de Linfocitos B/antagonistas & inhibidores , Inmunoconjugados/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Antígeno de Maduración de Linfocitos B/genética , Antígeno de Maduración de Linfocitos B/metabolismo , Médula Ósea/patología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Citometría de Flujo , Estudios de Seguimiento , Expresión Génica , Humanos , Inmunoconjugados/farmacología , Inmunohistoquímica , Mieloma Múltiple/genética , Mieloma Múltiple/metabolismo , Mieloma Múltiple/mortalidad , Células Plasmáticas/metabolismo , Células Plasmáticas/patología , PronósticoAsunto(s)
COVID-19/complicaciones , Mieloma Múltiple/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Formación de Anticuerpos , COVID-19/diagnóstico , COVID-19/inmunología , COVID-19/terapia , Prueba de COVID-19 , Vacunas contra la COVID-19/uso terapéutico , Femenino , Humanos , Inmunomodulación , Masculino , Persona de Mediana Edad , Mieloma Múltiple/inmunología , Mieloma Múltiple/terapia , SARS-CoV-2/inmunología , SARS-CoV-2/aislamiento & purificaciónAsunto(s)
Betacoronavirus , Infecciones por Coronavirus , Enfermedad Crítica , Pandemias , Neumonía Viral , COVID-19 , Humanos , SARS-CoV-2Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Anciano , Ensayos Clínicos como Asunto , Resistencia a Antineoplásicos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/patología , Recurrencia , Estudios Retrospectivos , Centros de Atención Terciaria , Resultado del TratamientoAsunto(s)
Antineoplásicos/uso terapéutico , Linfoma/tratamiento farmacológico , Mieloma Múltiple/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Femenino , Humanos , Estimación de Kaplan-Meier , Londres/epidemiología , Linfoma/mortalidad , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Pronóstico , Resultado del Tratamiento , Privación de Tratamiento/estadística & datos numéricosAsunto(s)
Antineoplásicos/uso terapéutico , Bortezomib/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Trasplante Autólogo/métodos , Adulto , Anciano , Antineoplásicos/farmacología , Bortezomib/farmacología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/patología , Recurrencia Local de Neoplasia , Calidad de Vida , Resultado del TratamientoRESUMEN
Bone marrow trephine biopsy is crucial for the diagnosis of multiple myeloma. However, the complexity of bone marrow cellular, morphologic, and spatial architecture preserved in trephine samples hinders comprehensive evaluation. To dissect the diverse cellular communities and mosaic tissue habitats, we developed a superpixel-inspired deep learning method (MoSaicNet) that adapts to complex tissue architectures and a cell imbalance aware deep learning pipeline (AwareNet) to enable accurate detection and classification of rare cell types in multiplex immunohistochemistry images. MoSaicNet and AwareNet achieved an AUC of >0.98 for tissue and cellular classification on separate test datasets. Application of MoSaicNet and AwareNet enabled investigation of bone heterogeneity and thickness as well as spatial histology analysis of bone marrow trephine samples from monoclonal gammopathies of undetermined significance (MGUS) and from paired newly diagnosed and posttreatment multiple myeloma. The most significant difference between MGUS and newly diagnosed multiple myeloma (NDMM) samples was not related to cell density but to spatial heterogeneity, with reduced spatial proximity of BLIMP1+ tumor cells to CD8+ cells in MGUS compared with NDMM samples. Following treatment of patients with multiple myeloma, there was a reduction in the density of BLIMP1+ tumor cells, effector CD8+ T cells, and regulatory T cells, indicative of an altered immune microenvironment. Finally, bone heterogeneity decreased following treatment of patients with multiple myeloma. In summary, deep learning-based spatial mapping of bone marrow trephine biopsies can provide insights into the cellular topography of the myeloma marrow microenvironment and complement aspirate-based techniques. SIGNIFICANCE: Spatial analysis of bone marrow trephine biopsies using histology, deep learning, and tailored algorithms reveals the bone marrow architectural heterogeneity and evolution during myeloma progression and treatment.
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Aprendizaje Profundo , Gammopatía Monoclonal de Relevancia Indeterminada , Mieloma Múltiple , Humanos , Médula Ósea/patología , Mieloma Múltiple/patología , Gammopatía Monoclonal de Relevancia Indeterminada/patología , Biopsia , Microambiente TumoralRESUMEN
In multiple myeloma (MM), early use of the immunomodulatory drug lenalidomide has led to an increased population of patients with lenalidomide-refractory MM in early-line settings, but their outcomes are not well characterized. Here, we report treatment patterns, survival outcomes, prognostic variables, and attrition rates for patients with proteasome inhibitor-exposed, lenalidomide-refractory MM, treated with 1-3 prior lines of therapy (LOT). From 12 767 patients with MM in the Flatiron Health database between January 2016 and April 2022, 1455 met the inclusion criteria. The most common subsequent treatments were triplet combinations (41.6% of patients); daratumumab/pomalidomide/dexamethasone was the most common treatment regimen (13.2%). Median real-world progression-free survival (RW-PFS) and overall survival (OS) were 6.5 months and 44.4 months, respectively. RW-PFS was similar in patients with 1, 2, or 3 prior LOT. International Staging System stage III, Eastern Cooperative Oncology Group performance status of 1, hemoglobin <12 g/dL, high-risk cytogenetics, and refractoriness to anti-CD38 antibody at baseline were associated with worse RW-PFS and OS. Outcomes remained similar for patients who received National Comprehensive Cancer Network-preferred treatments and those who received treatments after 2020. In 561 patients with 1 prior LOT at inclusion, cumulative attrition rate from LOT 2-5 was 85%, which included 25% patients who died and 60% with no further treatment. Patients with lenalidomide-refractory MM who have received 1-3 prior LOT have poor outcomes and progress rapidly through available therapies, highlighting the need for more effective treatments early in the disease course, before patients are lost to attrition.
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BACKGROUND: The humoral and T-cell responses to booster COVID-19 vaccine types in multidisease immunocompromised individuals who do not generate adequate antibody responses to two COVID-19 vaccine doses, is not fully understood. The OCTAVE DUO trial aimed to determine the value of third vaccinations in a wide range of patients with primary and secondary immunodeficiencies. METHODS: OCTAVE-DUO was a prospective, open-label, multicentre, randomised, controlled, phase 3 trial investigating humoral and T-cell responses in patients who are immunocompromised following a third vaccine dose with BNT162b2 or mRNA-1273, and of NVX-CoV2373 for those with lymphoid malignancies. We recruited patients who were immunocompromised from 11 UK hospitals, aged at least 18 years, with previous sub-optimal responses to two doses of SARS-CoV-2 vaccine. Participants were randomly assigned 1:1 (1:1:1 for those with lymphoid malignancies), stratified by disease, previous vaccination type, and anti-spike antibody response following two doses. Individuals with lived experience of immune susceptibility were involved in the study design and implementation. The primary outcome was vaccine-specific immunity defined by anti-SARS-CoV-2 spike antibodies (Roche Diagnostics UK and Ireland, Burgess Hill, UK) and T-cell responses (Oxford Immunotec, Abingdon, UK) before and 21 days after the third vaccine dose analysed by a modified intention-to-treat analysis. The trial is registered with the ISRCTN registry, ISRCTN 15354495, and the EU Clinical Trials Register, EudraCT 2021-003632-87, and is complete. FINDINGS: Between Aug 4, 2021 and Mar 31, 2022, 804 participants across nine disease cohorts were randomly assigned to receive BNT162b2 (n=377), mRNA-1273 (n=374), or NVX-CoV2373 (n=53). 356 (45%) of 789 participants were women, 433 (55%) were men, and 659 (85%) of 775 were White. Anti-SARS-CoV-2 spike antibodies measured 21 days after the third vaccine dose were significantly higher than baseline pre-third dose titres in the modified intention-to-treat analysis (median 1384 arbitrary units [AU]/mL [IQR 4·3-7990·0] compared with median 11·5 AU/mL [0·4-63·1]; p<0·001). Of participants who were baseline low responders, 380 (90%) of 423 increased their antibody concentrations to more than 400 AU/mL. Conversely, 166 (54%) of 308 baseline non-responders had no response after the third dose. Detectable T-cell responses following the third vaccine dose were seen in 494 (80%) of 616 participants. There were 24 serious adverse events (BNT612b2 eight [33%] of 24, mRNA-1273 12 [50%], NVX-CoV2373 four [17%]), two (8%) of which were categorised as vaccine-related. There were seven deaths (1%) during the trial, none of which were vaccine-related. INTERPRETATION: A third vaccine dose improved the serological and T-cell response in the majority of patients who are immunocompromised. Individuals with chronic renal disease, lymphoid malignancy, on B-cell targeted therapies, or with no serological response after two vaccine doses are at higher risk of poor response to a third vaccine dose. FUNDING: Medical Research Council, Blood Cancer UK.
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Vacuna BNT162 , Vacunas contra la COVID-19 , COVID-19 , Huésped Inmunocomprometido , Inmunogenicidad Vacunal , SARS-CoV-2 , Humanos , Femenino , Masculino , COVID-19/prevención & control , COVID-19/inmunología , Persona de Mediana Edad , Huésped Inmunocomprometido/inmunología , SARS-CoV-2/inmunología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Anciano , Vacuna BNT162/inmunología , Vacuna BNT162/administración & dosificación , Anticuerpos Antivirales/sangre , Estudios Prospectivos , Inmunización Secundaria , Vacuna nCoV-2019 mRNA-1273/inmunología , Adulto , Linfocitos T/inmunología , Reino Unido , ChAdOx1 nCoV-19/inmunologíaRESUMEN
BACKGROUND: Exercise programmes are beneficial for cancer patients however evidence is limited in patients with multiple myeloma (MM), a cancer that is characterised by osteolytic bone disease, giving rise to high levels of bone morbidity including fractures and bone pain. METHODS: We conducted a single arm phase 2 study of an exercise programme (EP) as rehabilitation for treated MM patients, to evaluate feasibility, effects on QOL and physiological parameters. Patients were given individualised programmes, comprising stretching, aerobic and resistance exercises, carried out under supervision for 3 months then at home for a further 3 months. RESULTS: Study uptake was high, 60 of 75 (80%) patients approached consented to the study. Screen failures (11, due to fracture risk and disease relapse) and patient withdrawals (12) resulted in a final 37 patients enrolling on the programme. These 37 patients demonstrated high attendance rates in the supervised classes (87%), and high levels of adherence in home exercising (73%). Patients reported better QOL following the EP, with improvement in FACT-G and Fatigue scores over time from baseline (p<0.01 for both, one-way repeated measures ANOVA) to 6 months. Upper and lower limb strength also improved on the EP, from baseline to 6 months (p<0.01 for both). There were no adverse reactions. CONCLUSIONS: An EP in MM patients is feasible and safe, with high attendance and adherence. Benefits in QOL, fatigue and muscle strength await confirmation in randomized studies, prompting urgent evaluation of the benefits of EP in the rehabilitation of MM patients.