PTJ: Physical Therapy & Rehabilitation Journal | Physical Therapy, 2021;101:1–10

DOI: 10.1093/ptj/pzaa180
Advance access publication date September 24, 2020
Clinical Practice Guidelines

Mobilization and Exercise Intervention for Patients With

Multiple Myeloma: Clinical Practice Guidelines
Endorsed by the Canadian Physiotherapy Association
Deepa Jeevanantham, PT, PhD1 ,2 , Venkadesan Rajendran, PT, PhD1 ,2 ∗ , Zachary McGillis, MHK3 ,
Line Tremblay, C.Psych, PhD4 , Céline Larivière, PhD5 , Andrew Knight, MD2
1 Health Sciences North, Sudbury, Ontario, Canada

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2 Northern Ontario School of Medicine, School of Human Kinetics, Laurentian University, Sudbury, Ontario, Canada
3 Laurentian University, Sudbury, Ontario, Canada
4 Clinical Sciences Division, Northern Ontario School of Medicine, Laurentian University, Sudbury, Ontario, Canada
5 Medical Sciences Division, Northern Ontario School of Medicine, School of Human Kinetics, Laurentian University, Sudbury, Ontario, Canada

*Address all correspondence to Dr. Jeevanantham at: djeevanantham@hsnsudbury.ca

Abstract
Objective. Individuals with multiple myeloma (MM) often have reduced functional performance due to the cancer itself or
as a direct side effect of cancer treatments. Physical therapy is a part of cancer rehabilitation; however, no guidelines are
available to provide information and direction for physical therapists managing patients with MM. The goal of this guideline
is to provide recommendations based on a systematic review and consensus process that physical therapists can use to
manage patients with MM.
Methods. A systematic review of the literature published until August 2018 was performed in 8 databases with 2 independent
reviewers assessing quality. Seventeen articles were identified as relevant, and a draft guideline was developed in the form
of action statements. A total of 10 physical therapists with hematology experience and 10 patients with MM were recruited
for consensus process. A priori threshold of 80% agreement was used to establish a consensus for each statement. The
draft guidelines were reviewed externally by 4 methodologists using the AGREE II tool and a stakeholder representing OH
(Cancer Care Ontario) Program in Evidence Based Care, McMaster University. The final guideline was reviewed and officially
endorsed by the Canadian Physiotherapy Association.
Results. A total of 30 action statements were developed that achieved consensus, indicating physical therapy recommen-
dations based on physiological markers (ie, hemoglobin, platelet count), complete patient presentation, and the stage of
medical treatment.
Conclusion. These clinical practice guidelines were developed to aid physical therapists in implementing evidence-based
and best-practice care for patients with MM to optimize rehabilitation outcomes.
Impact. These guidelines fill an important knowledge gap and are the first to provide information specifically for physical
therapist management of patients with MM.
Keywords: Guidelines, Oncology, Exercise Therapy, Clinical Guidelines

Received: June 18, 2020. Accepted: August 10, 2020

© The Author(s) 2020. Published by Oxford University Press on behalf of the American Physical Therapy Association.
This is an Open Access article distributed under the terms of the Creative Commons Attribution NonCommercial-NoDerivs licence (http://
creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium,
provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact
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2 Physical Therapy Management of Multiple Myeloma

Introduction were recovered after removing duplicates. Two independent

Patients with multiple myeloma (MM) may experience ane- reviewers (Z.M. and M.L.) carefully screened abstracts for
mia, thrombocytopenia, pancytopenia or neutropenia, bony inclusion, and 124 potential articles were selected for full-
lesions, or fractures at some point due to the cancer itself or text review. A total 109 articles were excluded (ie, abstracts
as a direct side effect of cancer treatments.1 Patients with this only, correlational studies, and irrelevance to guideline), and
presentation are typically admitted to hospitals for supportive the remaining 15 articles plus 2 additional articles (grey
treatments such as high-dose chemotherapy, autologous stem literature) were included for final guideline development
cell transplantation, antibiotics, blood transfusions, radia- (Figure). Each article was critically appraised (Z.M. and
tion therapy, and surgical interventions for pathologic and M.L.) using the standardized methodological assessment tool
impending fractures. Unfortunately, the side effects of these outlined in the study protocol.7 Supplementary Table 1 shows
medical treatments can negatively impact these individuals the study characteristics and the critical appraisal scores of
with symptoms such as increased fatigue, muscle weakness, each included article.
reduced muscle mass, reduced quality of life (QOL), and
increased sleep fragmentation.2–3 Drafting Action Statements

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Many of these symptoms can potentially be targeted with Completed in 2 parts: The initial draft AS were developed by
individualized exercise programs, which may aid in reduced 2 experienced oncology/hematology physical therapists after
cancer-related fatigue and muscle wasting,3 better sleep pat- reviewing supporting articles and guidelines (AS1–6). The
terns, and better QOL.4–6 Provided that patients receiving second set of AS (AS7–10) was based on data from the 17
treatment typically become physically inactive,2–3 it would included articles. Recommendations were made in the form
be imperative to mobilize these patients before, during, and of AS, along with levels of evidence and grades, as outlined in
after medical therapy to target any resulting deconditioning. the study protocol.7 An a priori threshold of 80% agreement
However, there is a lack of specific information to guide safe was used to establish a consensus for each AS, and a quality
mobilization and safe activity levels in patients with MM. A cut score of greater than 70% was set for AGREE II domains
scoping review revealed that there are no physical therapy– for consideration of the guidelines.8
specific guidelines available for exercise prescription before,
during, and after chemotherapy and stem cell transplantation. Expert Panel
Thus, the objectives of this study were to (1) develop a set of
Two groups of participants (physical therapists and patients
consensus-based recommendations to help physical therapists
with MM) were recruited for this study. The consensus pro-
make decisions on mobilization and exercise intervention of
cess was conducted in 2 phases. Phase I involved feedback
patients with MM in acute care settings, particularly based
from physical therapists and Phase II involved feedback from
on laboratory values (hemoglobin, platelet, and white blood
patients with MM. A total of 10 registered physical thera-
cell counts) and bony lesions; and (2) develop evidence-based
pists working in the public sector across Canada who were
recommendations for physical therapy management before,
experienced with oncology populations and able to read,
during, and after chemotherapy and stem cell transplantation
understand, and write in English were recruited for Phase
to improve strength, endurance, functional mobility, fatigue,
I of the consensus process. Of these, 4 physical therapists
increased nighttime sleep, and QOL in patients with MM.
were from Ontario, 2 from Winnipeg, 2 from Québec, and
1 from British Columbia and 1 from Alberta. The physical
Methods therapists’ work experience ranged from 4 to 27 years with
Design tremendous experience working with patients with MM. A
total of 10 patients diagnosed with MM admitted to 1 Ontario
A combination of systematic review, critical appraisal, and
hospital for cancer treatment and able to speak, read, write,
expert opinion was used for guideline development.
and understand English were recruited for phase II of the
Guideline Development Process consensus process. Participants (physical therapists) for phase
I were recruited by 1 investigator (V.R.) through a college
The guideline development steps recommended by the Amer-
of physiotherapy public registry. V.R. contacted potential
ican Physical Therapy Association were followed when draft-
participants, explained the study, answered questions, and
ing recommendations and determining levels of evidence.33
obtained consent through email. One physical therapist and 1
Recommendations for research questions with inadequate
patient withdrew from the study after initially consenting to
evidence were developed based on a consensus process.34
participate in the study. Phase I consensus process included 3
Recommendations were made in the form of action statements
rounds of email conversation, whereas Phase II involved only
(AS), and levels of evidence and grades of AS were determined
1 round of feedback from patients. Participants were asked to
using the recommendations of Kaplan and colleagues.35
mark either agree or disagree to the proposed statements and
Tables 1 and 2 outline the levels of evidence and grades of
to provide their comments for each statement.
recommendations. Refer to the study protocol for further
information about the guideline development process.7
Results of the Consensus Process
Review of Literature A total of 32 AS including sub-statements were sent for Phase
A literature search strategy was developed and performed I of the consensus process to receive feedback from physical
by 2 research assistants (M.L. and Z.M.), as outlined in the therapists. In the first round, 16 items (item nos. 4c, 4d, 4e,
study protocol, to understand the research evidence around 5b, 7, 8, 8d, 9, 9a, 9b, 9c, 9d, 10, 10a, 10b, and 10c) received
the physical therapy management of MM.7 In brief, a reviewer 100% consensus to include, 9 items (item nos. 1, 2, 4, 4a,
(Z.M.) systematically searched databases and retrieved 4f, 5a, 8a, 8b, and 8c) received 89% consensus to include,
48,060 articles with EndNote software, and 28,679 articles 3 items (item nos. 3, 5c, and 4b) received 78% consensus to
Jeevanantham et al 3

Table 1. Levels of Evidencea

Level Criteria
I Evidence obtained from high-quality diagnostic studies, prognostic or prospective studies, cohort studies or randomized controlled
trials, meta analyses or systematic reviews (critical appraisal score >50% of criteria)
II Evidence obtained from lesser-quality diagnostic studies, prognostic or prospective studies, cohort studies or randomized controlled
trials, meta analyses or systematic reviews (eg, weaker diagnostic criteria and reference standards, improper randomization, no
blinding, <80% follow-up) (critical appraisal score <50% of criteria)
III Case-controlled studies or retrospective studies
IV Case studies and case series
V Expert opinion
a
Reprinted from Kaplan S, Coulter C, Fetters L. Developing evidence-based physical therapy clinical practice guidelines. Pediatr Phys Ther. 2013;25:257–
270, with permission of Wolters Kluwer Health Inc. The Creative Commons license does not apply to this table. Use of the material in any format is
prohibited without written permission from the publisher, Wolters Kluwer Health, Inc. Please contact permissions@lww.com for further information.

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Table 2. Definition of Grades of Recommendation for Action Statementsa

Grade Recommendation Quality of Evidence

A Strong A preponderance of level I studies, but at least 1 level I study directly on the topic support the
recommendation
B Moderate A preponderance of level II studies but at least 1 level II study directly on topic support the
recommendation
C Weak A single level II study at <25% critical appraisal score or a preponderance of level III and IV
studies, including statements of consensus by content experts support the recommendation
D Theoretical/foundational A preponderance of evidence from animal or cadaver studies, from conceptual/theoretical
models/principles, or from basic science/bench research, or published expert opinion in
peer-reviewed journals supports the recommendation
P Best practice Recommended practice based on current clinical practice norms, exceptional situations where
validating studies have not or cannot be performed and there is a clear benefit, harm, or cost,
and/or the clinical experience of the guideline development group
R Research There is an absence of research on the topic, or higher-quality studies conducted on the topic
disagree with respect to their conclusions. The recommendation is based on these conflicting or
absent studies.
a
Reprinted from Kaplan S, Coulter C, Fetters L. Developing evidence-based physical therapy clinical practice guidelines. Pediatr Phys Ther. 2013;25:257–
270, with permission of Wolters Kluwer Health Inc. The Creative Commons license does not apply to this table. Use of the material in any format is
prohibited without written permission from the publisher, Wolters Kluwer Health, Inc. Please contact permissions@lww.com for further information.

include, and 1 item (item no. 6) received only 67% consensus and research experience, with 3 having a physiotherapy back-
to include. The focus group recommended rewording some ground and 1 with a nursing background. All methodologists
sentences and including additional precautions for a few of recommended this guideline for use (Tab. 3).
the items. Accordingly, the statements were revised based on
the feedback from the physical therapists. The research team Stakeholder Involvement
decided to include item numbers 3, 5c, and 4b, which received Methodological feedback on a draft document was provided
78% consensus. One item (no. 6) was completely revised that by a stakeholder representing the OH (Cancer Care Ontario)
received only 67% consensus and sent for a second round of Program in Evidence Based Care, McMaster University. The
consultation. The item was revised based on feedback and final guideline was reviewed and officially endorsed by the
was sent for a third round and received 89% consensus for Canadian Physiotherapy Association.
inclusion in the final guideline. Our research team decided
to eliminate 1 AS (acupuncture for pain relief during or after
medical treatment) during the first round because the majority Discussion
of the physical therapists reported that they did not have Hemoglobin
expertise in acupuncture treatment. A total of 30 AS were
Physical therapist intervention is generally contraindicated
developed that achieved consensus (Suppl. Table 2).
in patients with hemoglobin values less than 8 g/dL.9 It is
The revised guideline was sent for Phase II of the consen-
recommended to take precautionary measures but not to
sus process to receive input from patients with MM. The
withhold physical therapy for patients with hemoglobin levels
participants were asked to read each statement and provide
lower than 8 g/dL.9 Evidence shows that patients with levels
their input in the comment box beside each statement. All 10
as low as 7 g/dL (HgB level) can tolerate physiotherapy,
patients “agreed” with the recommended statements and pro-
but those patients with cardiac and respiratory conditions
vided positive comments. None of the patients gave negative
are at a higher risk of compromised cardiac output and
comments or recommended to modify the statements.
desaturation.10 Stiller and Phillips11 recommend withholding
mobilization for patients with levels lower than 7 g/dL.
AGREE II Review Therefore, while providing care for patients with lower
As per recommendation, 4 methodologists were identified to hemoglobin levels (<8 g/dL), physical therapists should
review these clinical practice guidelines to increase the relia- monitor vital signs and signs of adverse events (ie, chest pain,
bility of the assessment.8 These methodologists have clinical pallor, leg cramps, dizziness, arrhythmias, shortness of breath,
4 Physical Therapy Management of Multiple Myeloma

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Figure. Preferred Reporting Items for Systematic Reviews (PRISMA) flow diagram.

respiratory distress, SBP > 200 mmHg or DBP > 110 mmHg, RBCs. Withholding physical therapy solely on the basis of
drop in SBP > 10 mmHg from the baseline, heart rate an RBC transfusion might affect patients’ mobility and func-
increases >120 bpm with activity, SpO2 levels <88% with tional status. It is reported that patients’ receiving physical
activity, and/or a positive orthostatic response). Lastly, it is therapist intervention during RBC transfusion did not have
strongly recommended that physical therapists liaise with any adverse events.11 It is recommended that patients be mon-
physicians before delivering physical therapist interventions itored closely for abnormal vital signs and other events (ie,
and discuss any additional signs to monitor during therapy dislodging of intravenous site, syncope, and reaction to blood
sessions. products).12

Blood Transfusion Platelets

Patients with MM typically receive a transfusion of red blood Typically, platelet counts may drop following chemotherapy
cells (RBC) when the Hb concentration is lower than 7 g/dL with the lowest count occurring 7 to 10 days post chemother-
in stable adults or lower than 8 g/dL in those with cardiac apy and take 2 to 3 weeks to recover. While bed rest is
issues. Patients may receive a transfusion for approximately important in preventing bleeding, multiple weeks of bed rest
2 to several hours depending on the number of units of may cause significant functional decline in older patients with
Jeevanantham et al 5

Table 3. AGREE II Domain Scores and Recommendations for Use of This Guidelinea

AGREE II Domains Reviewer 1 Reviewer 2 Reviewer 3 Reviewer 4 Domain Scoresb,c

(%)
Scope and purpose (total score 21 21 21 21 100
of 3 items)
Stakeholder involvement (total 21 21 18 19 93
score of 3 items)
Rigor of development (total 56 55 54 51 94.8
score of 8 items)
Clarity of presentation (total 21 19 21 19 94.4
score of 3 items)
Applicability (total score of 4 25 26 28 20 86.4
items)
Editorial independence (total 14 14 14 14 100
score of 2 items)

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Overall quality of guideline 7 6 6 6 87.5
Recommended for use Yes Yes Yes Yes
a b
Quality of guideline score ranges from 1 (lowest possible quality) to 7 (highest possible quality). Domain scores were calculated as per the scoring
c
criteria outlined in the AGREE II tool.8 Domain scores of ≥70% considered a high-quality guideline.8

MM. Therefore, it is important to consider the benefits and recommendations for persons with chronic diseases and
harms of exercise to prevent functional decline. disabilities)14 recommend exercises using elastic bands in
There is not a low limit cut-off for suspending all phys- patients with platelet counts between 20,000 and 50,000/μL.
ical activity in patients with thrombocytopenia, particularly Given the variation of the population for which the above
in patients undergoing chemotherapy.14 The Leukemia/Bone guidelines are recommended, we suggest light resistance
Marrow Transplant Program of British Columbia (L/BMT exercises using elastic bands if no signs of bleeding without
program of BC) recommends limited physical activity when strain for patients with MM with platelets between 20,000
platelet counts are <15,000/μL; however, Sekhon and Roy13 and 40,000/μL. It is also recommended that exercises be
reported risk of bleeding with counts <10,000/μL. Interest- performed without strain to avoid bleeding due to possible
ingly, these authors also report that platelet count is an impre- spikes in blood pressure.
cise predictor of bleeding risk. Overall, given that platelets are We recommend gentle aerobic activity, including station-
typically transfused when the platelet count is <10,000/μL, ary cycling in patients with platelets >40,000/μL in com-
we recommend only essential ambulation (ie, bathroom) with pliance with the L/BMT program of BC. In addition, we
counts <10,000/μL. Assistance/supervision and gentle range recommend avoiding vigorous exercises in patients with levels
of motion (ROM) in sitting or lying are recommended to <50,000/μL in compliance with ACSM and proper use of
prevent bleeding due to a fall. clothing and equipment to prevent bleeding from trauma.
The L/BMT program of BC recommends gentle exercises Therefore, we recommend that physical therapists monitor
without resistance for patients having platelet counts between for signs of bleeding and educate patients about these signs
15,000 to 20,000/μL. The Seattle Cancer Care Alliance recom- and precautions for prevention. It would be ideal to liaise with
mends strength training and cardiovascular exercises without physicians as well regarding physical therapist interventions
resistance and strain for patients with platelet levels between as only a slender line exists between bed rest for preventing
10,000 and 19,999/μL.15 Neal et al16 conducted a retro- bleeding and exercise/physical activity to prevent functional
spective cross-sectional study in 119 patients with cancer decline in adults with MM admitted in acute care settings. It
admitted to an acute inpatient rehabilitation facility with is recommended physical therapists use their discretion and
at least 1 with a platelet count of <150,000/μL. Of the clinical judgment in this decision making.
119 patients, 49 had hematologic cancer and there were 56
bleeding events. Interestingly, a higher number of bleeding Neutropenia
events (35/56) occurred when the platelets were 51,000/μL Neutropenia is often present in patients with MM and is
or greater, and these events were not associated with very low an expected side effect following chemotherapy. Although
counts (<11,000 or 11,000–20,000/μL), all of which suggest asymptomatic neutropenia is not a medical emergency, neu-
that patients with cancer can safely undergo inpatient reha- tropenia increases the risk of infection.18 Febrile neutrope-
bilitation even with low platelet counts.16 Therefore, we rec- nia is an oncologic medical emergency, and patients with
ommend gentle ROM and strength-training exercises without febrile neutropenia are often hospitalized for treatment. There
resistance and without strain for patients with platelet levels are no specific exercise recommendations for patients with
between 10,000 and 20,000/μL to avoid bleeding from high leukopenia and neutropenia; therefore, we recommend the
exertional blood pressure. Exercise in standing and ambula- following for physical therapy in this population to prevent
tion is recommended for platelet levels between 10,000 and infection. Patients with MM with neutropenia or leukopenia
20,000/μL only if the patient is steady on his/her feet with or are immunocompromised, and the use of face masks (barrier
without assistive devices and has no signs of bleeding. for microorganism entry) and regular hand hygiene can reduce
The L/BMT program of BC recommends light resistance their risk of infection. We recommend that patients with
exercises for patients with platelet levels between 20,000 and MM wear a face mask when ambulating in the hallways and
40,000/μL.17 However, the Seattle Cancer Care Alliance38 and to wash hands properly before and after sessions. Physical
the American College of Sports Medicine (ACSM) (exercise therapy equipment and assistive devices should be routinely
6 Physical Therapy Management of Multiple Myeloma

sanitized before and after use by patients, and physical ther- Sleep and Fatigue Benefits
apist intervention should be conducted individually in the The research regarding sleep and fatigue outcomes involves
patient’s room to avoid infection and the consequences asso- strictly home-based, individualized exercise programs during
ciated with it.19 medical therapy.5,28 The results suggest that these exercise
interventions (low-intensity aerobic/strengthening exercise)
during treatment can decrease fatigue and increase total
Bony Lesions minutes and percentage of sleep. This highlights that exercise
Patients with MM present with myeloma bone disease affect- may aid with deconditioning and recovery time,5,25,27 which
ing any part of the skeleton, resulting in bony pain and may positively impact psychosocial well-being of these
increased risk of fractures. Bone destruction is primarily medi- patients.26,28
ated by osteolytic metastasis,20 and it is estimated that 70% to
80% of patients with MM suffer from bone pain, 50% to 60% Fatigue and QOL Benefits
have fractures, and 2% to 3% have spinal cord compression
Multiple studies have explored psychosocial factors during25
leading to increased morbidity, poor mobility, and decreased 27 or after medical therapy.30–32 The research supporting this
QOL.21 Evidence supports that exercise improves physical

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guideline for during medical treatment periods tends to incor-
function in patients with cancer, but additional precautions
porate supervised, multimodal, low-intensity aerobic and/or
and modifications are necessary in developing an exercise
strength/resistance-training regimens, all tailored to individual
regimen in this population. Bony lesions are not absolute
needs. Although the studies were review based25 or had a
contraindications to physical therapy intervention; however,
mixed hematological cancer sample,27 the results identify
components of exercise prescription should be modified and
that patients undergoing medical treatment who are exercise-
additional precautions should be followed to minimize the
compliant tend to experience reduced fatigue and better QOL,
risk of fractures (ie, avoiding high-impact activities, end range
particularly in physical functioning. After medical treatment,
movements, ie, hyper- and rotational movements, that increase
these patients embrace deconditioning and enter the recovery
compressive and shearing forces, follow back care principles,
phase. Multiple studies met the criteria for inclusion.30–32
and use appropriate mobility aids and braces).22 Physical
These programs utilized a combination of high- or low-
therapists should be cautious in designing exercises as twisting
intensity exercise with both supervised and/or unsupervised
movements, forward bending, overhead reaching, pushing,
sessions to understand the impact on psychosocial well-being.
pulling, and lifting weights can cause or worsen vertebral
Although no significant differences were identified, all studies
fractures in patients with bony lesions. It is also recom-
highlight decreased fatigue and better QOL than usual care.
mended that physical therapists use their clinical judgment
With little to no adverse events, it would be recommended to
and expertise to modify components of programs to fit patient
follow a tailored exercise program during and after treatment
needs.
to aid with recovery and deconditioning by improving psy-
chosocial aspects of the patients’ lives.
Psychosocial Benefits (Sleep, Fatigue, QOL) The results of the studies above highlight the importance
of exercise during and after medical therapy to positively
Exercise for patients with MM may be important and
influence the mental well-being of the patient. Although some
beneficial before, during, and after medical treatment given
of the research obtained above involves mixed MM and hema-
that exercise, for those with and without cancer, can reduce
tological samples, the similar treatment pathways suggest that
fatigue and muscle wasting and increase QOL.3,6 The first
the results may be applicable to patients with MM. Of note,
phase (peri-transplant) may be an opportunistic period before
study limitations (mixed and small samples, contamination
deconditioning as the benefits of increased fitness may reduce
of control group, etc.) must be considered prior to prescrib-
treatment-related recovery time,23 creating a platform for
ing exercise to patients with MM during and post-medical
better sleep, less fatigue, and better QOL. Unfortunately,
therapy. However, given the benefits described above, along
limited research is available during this phase.23,24 The
with a low risk of harm to the patient, the results suggest
next phase of the treatment pathway is medical therapy,
that clinicians may prescribe exercise to reduce sleep, fatigue,
another critical period for patients with MM both for
and QOL issues, pending individualized considerations are
combating the disease symptoms as well as treatment-related
met. Further, it was identified that patients with skeletal issues
symptoms (poor sleep, increased fatigue, and physical/mental
can exercise safely but may ultimately require supervision and
health declines).3–6 A limited number of research articles
thoughtful modifications to their exercise regimen.
report on exercise programs for patients with MM during
treatment.5,24–28 The last phase, or post-treatment phase, is
Physical Benefits (Exercise Adherence, and
again a different but critical recovery period. The treatment-
related deconditioning, increased fatigue, and reduced QOL
Functional Mobility and Performance)
could all negatively impact the patient physically and mentally. Exercise before, during, and after medical treatment may
Multiple studies have assessed the effects of mixed training be difficult due to the disease process and/or the aggressive
programs during this phase.29,31,32 Provided that therapy- debilitating side effects. As such, a limited number of articles
related deconditioning may result in worsened sleep, fatigue, reported physical outcomes of mixed exercise programs for
and QOL, it is important to implement guidelines that patients with MM before,24 during,5,25–30 and after medical
may reduce the psychosocial impact. Standard treatment therapy.30–32
guidelines typically call for bedrest during this phase; however,
a more physical activity–based routine may be required Exercise Adherence
to reduce recovery time and aid with these psychosocial Before undergoing medical therapy may be the most oppor-
aspects. tune time to increase aerobic capacity and strength, thereby
Jeevanantham et al 7

aiding with the impending deconditioning and recovery pro- already complex health situation. Further, those with skeletal
cess. The research for patients with MM in this phase is issues can still exercise but may require supervision and moti-
limited, but the results suggest that it is safe and feasible as vation to follow through with any program. Overall, these
an unsupervised program; however, compliance with strength studies have limitations (ie, retrospective design, small/mixed
training was minimal.23,24 Aerobic training in the form of sample sizes), but the trends support both supervised/unsuper-
walking may be the preferred modality yet may not provide vised and tailored exercise for this population during all stages
enough benefit, compared with resistance and high-intensity of the treatment protocol, and, generally speaking, this can be
training, for these patients.24 More research is required in this inexpensive and require minimal resources while potentially
phase to understand the impact of exercise in the later stages providing multiple physical and mental benefits.
of the treatment pathway.

Functional Mobility and Performance Benefits New and Current Research

Many studies highlight the physical benefits of exercise dur- A quick scoping review was conducted in June 2020 by
ing and after medical treatment. Functional mobility during 1 of the original investigators (Z.M.) to identify any new

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and after deconditioning is an important aspect of recovery, evidence supporting or conflicting with the current views
as these patients need the strength and aerobic capacity to of this guideline. The review uncovered 8 articles that met
function with all activities of daily living. During treatment, the inclusion criteria set for the current guideline. Of note,
these patients will typically become inpatients, and supervised these articles were not included in the current guideline devel-
exercise or rehabilitation may be implemented at this time. opment process but will be included in the 2025 guideline
The evidence suggests that this is feasible as no adverse update.
events for either aerobic or strength training exercises were In terms of interventional studies, the results highlight
reported,24–26 with potential for functional mobility and self- similar trends as mentioned throughout this guideline. With
care improvements to aid with repatriation to the home regards to feasibility, multiple studies deemed exercise pre-
environment.26 treatment and during medical treatment to be successful
Multiple studies have reviewed more specific performance- (excellent adherence rate, no adverse events), particularly
related outcomes for exercise during the treatment phase, as a positive emotional impact prior to the decondition-
both with full MM samples5,28,29 and mixed hematologi- ing.36,38,39,41 Other studies assessing exercise during and
cal cancer samples.28,30,33 These studies incorporate home- post medical treatment focused highly on individualized
based or supervised, tailored exercise programs on physical exercise in which daily laboratory values were utilized to
performance benefits (aerobic capacity, muscular strength, make exercise adjustments. With outcomes focused on fatigue,
and physiological changes). As expected, all patients typically fitness, and QOL, the trends suggest that exercise can be
experienced declines in physical performance, yet the trends beneficial, supporting the current guideline in that exercise
suggest that exercise, if adhered to, reduces this impact, allow- may have a multimodal positive or neutral effect throughout
ing patients to maintain close to baseline scores.5,29,30 Specif- the deconditioning process.37,39–41 These recent findings
ically, these programs may allow for an increase in aerobic further extend our understanding that this patient population
capacity and muscular strength compared with usual care27 requires highly individualized exercise to optimize their
and, not surprisingly, support a higher rating of good overall treatment pathway. In terms of new research, a study found
condition, more physical activity, and better integration into that inspiratory muscle training plus conventional physical
daily life. therapy may aid with reduced negative symptoms (ie, less need
The last phase of the treatment pathway, post-therapy, for oxygen therapy) compared with conventional physical
incorporates 2 accepted studies.31,32 Home-based, tailored therapy alone.40 The current guideline does not explore
programs can benefit patients in terms of strength, body inspiratory breathing specifically, and thus these results pose
composition, and physical activity. The clinically important an interesting new pathway for future research.
trends highlighted that more patients had maintenance of The results of the 2 meta-analyses42,43 suggest that exercise
body composition and higher rate of weekly physical activity, has a neutral or positive effect on most outcomes studied in
again with aerobic training (walking) as a preference. In the literature thus far, with more possible positive effects on
terms of strength, all patients experienced a decline from muscle strength,43 fatigue,42,43 and QOL.42,43 A subgroup
baseline, but those who exercised had a less severe decline. analysis also suggests pre-transplant exercise has a favorable
The research for post-treatment exercise suggests benefits of effect on upper/lower body muscle strength, fatigue, and
early intervention for stable, mixed hematological patients to QOL, but there were no effects on anything except QOL
support early recovery. for all other treatment stages.43 Interestingly, the results from
The evidence for physical benefits of exercise before, during, Knips and colleagues42 suggest no clear evidence on the
and after treatment exists for patients with MM. These mixed, majority of outcomes but indicate that the number and size
individualized exercise programs may create a stronger phys- of trials need to increase significantly. Unfortunately, there is
ical base prior to treatment and reduce the impact during the still minimal literature in this field, and this limits the results of
deconditioning phase, possibly reducing recovery time. With both of these meta-analyses. In addition, Mohammed et al44
multiple articles suggesting this patient population can adhere conducted a literature review and developed a protocol for
to a tailored regimen, we recommend that physical thera- patients undergoing hematopoietic stem cell transplantation,
pists utilize these guidelines to develop physical activity-based and it supports the recommendations proposed by our group.
treatment plans at all stages of the medical therapy pathway. Since August 2018, the published studies generally support
It is clear however, that they must take into consideration all the evidence for individualized exercise throughout the treat-
aspects of the patient’s health when determining these plans in ment process in this patient population. The current guideline
order to avoid unnecessary injury or complications during an has evidence to suggest that exercise is important throughout
8 Physical Therapy Management of Multiple Myeloma

the treatment process to combat deconditioning, of which the Clerical/secretarial support: D. Jeevanantham, V. Rajendran
most recent research furthers our understanding. As most of Consultation (including review of manuscript before submitting):
the newly published research are feasibility studies, there is a D. Jeevanantham, V. Rajendran, C. Larivière, L. Tremblay, Z. McGillis,
need for large, randomized, and multicenter studies for strictly A. Knight
patients with MM. This said, the topic of individualized
exercise across the treatment pathway for patients with MM
is continuously moving forward, and the results suggest that Acknowledgments
it is feasible, safe, and effective for this patient population. Our special thanks to the Canadian Physiotherapy Association
and the Program in Evidence Based Care, McMaster University, and
Dr Sathish Kumar Gopalakrishnan, Hematologist at Health Sciences
Implementation Recommendations North, for providing feedback. We extend our thanks to the following
These guidelines included a physical therapist intervention consensus panel members and AGREE II reviewers. Consensus panel
members: Trudy Weir, Foothills Medical Center; Kei Nishikawa,
in multiple settings, such as acute care, outpatient depart-
Vancouver General Hospital; Karen Dobbin, Cancer Care Manitoba;
ment, and home environment, and these variables may affect Lyne Marum, Ottawa Hospital; Jessie Koopman, Juravinski Hospital

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the translation of evidence into practice. Physical therapists and Cancer; Marize Ibrahim, Jewish General Hospital; Shirin Mehdi
should assess their own practice environment and use their Shallwani, School of Rehabilitation Sciences, University of Ottawa,
clinical skills to implement the AS based on patients’ needs. & McGill University Health Centre Lymphedema Program; Lukas
We recommend that the following strategies be implemented Hildebrand, Winnipeg Health Sciences Centre; Claire Brooks, London
in practice: (1) keep a copy of these guidelines at your practice; Health Sciences Centre. AGREE II reviewers: Dr Margaret McNeely,
(2) share these guidelines with your peers (physical therapists) PhD PT, Professor of Rehabilitation Medicine (Oncology and Physical
and patients, and with the physicians, oncologists, and hema- Therapy), University of Alberta; Dr Oren Cheifetz, PT PhD, Assistant
tologist of your patients who are interested in learning about Clinical Professor, Rehabilitation Science, McMaster University, and
Clinical Specialist in Oncology Physiotherapy (Canadian Physiotherapy
physical therapy for MM; and (3) build relationships with
Association); Dr Jayaprakash Raman, PT PhD, Assistant Professor (Part
referral sources to encourage early referrals of patients with time), Faculty of Health Sciences, Western University, and Assistant
MM. We are planning to revise these guidelines in 2025 based Clinical Professor (Adjunct), Rehabilitation Science, McMaster
on the feedback from physical therapists and their patients University; Dr Roger Pilon, PhD, Nurse Practitioner, Assistant Professor,
and findings from updated literature reviews. School of Nursing-Faculty of Health, Laurentian University.

Funding
Strength and Limitations
This study was reviewed and funded by the Northern Ontario Academic
This guideline was developed with a combination of sys-
Medicine Association (Project C-17-11). The funding bodies played no
tematic review and critical appraisal as well as with expert role in developing the guidelines.
opinion. In this sense, the guideline may lack adequate evi-
Z. McGillis was supported by a research assistantship from the
dence, particularly with the latter. However, to increase the
NOAMA grant (Project C-17-11).
merit of this guideline, a multidisciplinary team was utilized.
This team consisted of researchers, physical therapists (with
oncology/hematology experience), an exercise physiologist, Ethics Approval
a physician, and a direct consultation with a hematologist.
The ASs were also reviewed by physical therapists with spe- The Research Ethics Board of Health Sciences North Research Institute
cific experience in treating patients with MM, which further approved this study.
strengthens the validity of the guideline. Furthermore, this
guideline was reviewed and rated by methodologists with Disclosures
clinical and research experience in oncology.
None of the consensus panel members and external reviewers disclosed
competing interests. The authors completed the ICMJE Form for Dis-
Author Contributions closure of Potential Conflicts of Interest and reported no conflicts of
interest.
Concept/idea/research design: D. Jeevanantham, V. Rajendran,
C. Larivière, A. Knight
Writing: D. Jeevanantham, V. Rajendran, C. Larivière, L. Tremblay,
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