The effects of short-term, progressive exercise training on disease activity in smouldering multiple myeloma and monoclonal gammopathy of undetermined significance: a single-arm pilot study

Abstract

Background: High levels of physical activity are associated with reduced risk of the blood cancer multiple myeloma (MM). MM is preceded by the asymptomatic stages of monoclonal gammopathy of undetermined significance (MGUS) and smouldering multiple myeloma (SMM) which are clinically managed by watchful waiting. A case study (N = 1) of a former elite athlete aged 44 years previously indicated that a multi-modal exercise programme reversed SMM disease activity. To build from this prior case study, the present pilot study firstly examined if short-term exercise training was feasible and safe for a group of MGUS and SMM patients, and secondly investigated the effects on MGUS/SMM disease activity.

Methods: In this single-arm pilot study, N = 20 participants diagnosed with MGUS or SMM were allocated to receive a 16-week progressive exercise programme. Primary outcome measures were feasibility and safety. Secondary outcomes were pre- to post-exercise training changes to blood biomarkers of MGUS and SMM disease activity- monoclonal (M)-protein and free light chains (FLC)- plus cardiorespiratory and functional fitness, body composition, quality of life, blood immunophenotype, and blood biomarkers of inflammation.

Results: Fifteen (3 MGUS and 12 SMM) participants completed the exercise programme. Adherence was 91 ± 11%. Compliance was 75 ± 25% overall, with a notable decline in compliance at intensities > 70% V̇O_2PEAK. There were no serious adverse events. There were no changes to M-protein (0.0 ± 1.0 g/L, P =.903), involved FLC (+ 1.8 ± 16.8 mg/L, P =.839), or FLC difference (+ 0.2 ± 15.6 mg/L, P =.946) from pre- to post-exercise training. There were pre- to post-exercise training improvements to diastolic blood pressure (- 3 ± 5 mmHg, P =.033), sit-to-stand test performance (+ 5 ± 5 repetitions, P =.002), and energy/fatigue scores (+ 10 ± 15%, P =.026). Other secondary outcomes were unchanged.

Conclusions: A 16-week progressive exercise programme was feasible and safe, but did not reverse MGUS/SMM disease activity, contrasting a prior case study showing that five years of exercise training reversed SMM in a 44-year-old former athlete. Longer exercise interventions should be explored in a group of MGUS/SMM patients, with measurements of disease biomarkers, along with rates of disease progression (i.e., MGUS/SMM to MM).

Registration: https://www.isrctn.com/ISRCTN65527208 (14/05/2018).

Keywords: Aerobic exercise; Anti-cancer mechanisms; Cancer precursors; Cancer risk; Exercise oncology; Resistance exercise.

Fig. 1

CONSORT diagram showing flow of participants through the pilot trial Missing data: DEXA (N = 1 participant declined radiation exposure); grip strength and upper limb flexibility (N = 1 did not attend for follow-up fitness measurements); lower limb flexibility (N = 1 did not attend for follow-up fitness measurements, N = 1 unable to perform due to lower limb pain at follow-up assessment); cardiorespiratory fitness, functional balance, lower body strength (N = 1 did not attend for follow-up fitness measurements, N = 2 unable to perform due to lower limb pain at follow-up assessment). MM = Multiple myeloma; CPET = Cardiopulmonary exercise test; DEXA = Dual-energy x-ray absorptiometry

Fig. 2

Pre- to post-exercise training changes to disease biomarkers in subgroups with a high vs. low baseline physical activity level. Pre- to post-exercise training changes to M-protein (A), involved FLC (B), and FLC difference (C) in subgroups of participants with a high baseline PAL (≥ 1.75) or low baseline PAL (< 1.75). Block bars show the median, and error bars show IQR. Lines joining circles show individual responses. PAL = Physical activity level; FLC = Free light chains

Fig. 3

Individual changes to disease biomarkers of MGUS and SMM from pre- to post-exercise training. (A) Individual changes to M-protein shown in the context of physiological variation to M-protein during monitoring of stable disease (CV 7.8%) [35] shown in grey. (B) Individual changes to M-protein shown in the context of historical disease activity measurements accessed from medical records. Intervention period shown in grey. (C) Individual changes to involved FLC shown in the context of physiological variation to involved FLC during monitoring of stable disease (CV 27.8%) [35] shown in grey. (D) Individual changes to involved FLC shown in the context of historical disease activity measurements accessed from medical records. Intervention period shown in grey. High baseline physical activity level defined as PAL ≥ 1.75. Low baseline physical activity level defined as PAL < 1.75. In panel B and D, three-year disease history was available and, as the frequency of disease monitoring between participants varied, time-points were arbitrarily assigned 0–12 in order to align the intervention period in all participants. In panel B and D, where M-protein and involved FLC are shown to decrease in one participant between timepoints 5–7, it should be noted that this participant received treatment for prostate cancer during that period. FLC = Free light chains

Fig. 4

Percentage change to inflammatory biomarkers from pre- to post-exercise training Block bars are median percentage change from pre- to post-exercise training and error bars are IQR. Individual changes are shown in open circles. All N = 15, excluding IL-1RA (N = 10). All biomarkers are measured in plasma, except for CRP which was measured in serum. IL = Interleukin; RA = Receptor antagonist; CRP = C-reactive protein; VEGF = Vascular endothelial growth factor; sIL-6Rα = Soluble IL-6 receptor alpha; TNF-α = Tumour necrosis factor alpha