Treatment

Document Overview

Design and created by Guideline Central in participation with the American Society of Clinical Oncology and Cancer Care Ontario.

Treatment of Multiple Myeloma

American Society of Clinical Oncology

Cancer Care Ontario

Publication Date: Jan 6, 2026

Page Last Updated: May 5, 2026

Recommendation 4.3.

riplet therapy or T-cell redirecting therapies should be offered to eligible patients with relapsed/refractory multiple myeloma based on the following principles:
- Whenever possible, patients should be offered treatment regimens that include agents that are different than those in their prior therapies.
- Triplets should be offered to eligible patients. See text for details on evidence-based triplet regimens.
- Chimeric antigen receptor (CAR) T-cell therapy should be offered to eligible patients. A thorough patient-centered discussion regarding the risks, benefits, and timing of CAR T-cell therapy is advised.
- Patient preferences with respect to toxicity tolerance, dose and schedule convenience, and means of administration should be factored in with shared decision making when deciding between triplet or CAR T-cell therapy.
- CAR T-cell therapy may not be appropriate for patients with rapidly progressive relapsed myeloma given the time required for CAR T-cell manufacturing. In this setting, an agent that is immediately available may be favored over CAR T-cell therapy.
- If the patient is unable to receive triplet or CAR T-cell therapy (based on tolerability, frailty, access, etc.), doublet therapy is reasonable.
- Bispecific antibodies should be offered to eligible patients (including older and frail patients).
- The optimal sequencing of therapy is an evolving consideration. In the context of a limited evidence base, sequencing decisions should be made based on patient factors, disease characteristics, mechanism of action, and prior treatment responses.
- Patients for whom existing options have been exhausted or for whom the risks are likely to outweigh the benefits should be offered best supportive care and hospice referral.

(Evidence quality: High for primary recommendation in first sentence to offer triplet or T-Cell redirecting therapies, individual bullet points vary in certainty; Strength of recommendation: Strong for first sentence; Conditional for principles.) ( H, S )

Recommendation Rating Definitions

Quality of Evidence
Term		Definitions
H	- High	We are very confident that the true effect lies close to that of the estimate of the effect
M	- Moderate	We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
L	- Low	Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect.
VL	- Very Low	We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.

Strength of Recommendation
Term		Definitions
S	- Strong	In recommendations for an intervention, the desirable effects of an intervention outweigh its undesirable effects. In recommendations against an intervention, the undesirable effects of an intervention outweigh its desirable effects. All or almost all informed people would make the recommended choice for or against an intervention.
W	- Weak	In recommendations for an intervention, the desirable effects probably outweigh the undesirable effects, but appreciable uncertainty exists. In recommendations against an intervention, the undesirable effects probably outweigh the desirable effects, but appreciable uncertainty exists. Most informed people would choose the recommended course of action, but a substantial number would not.

GRADE Handbook, Schünemann, et al. 2013.

Document Overview

Document Title: Treatment of Multiple Myeloma

Authoring Societies

American Society of Clinical Oncology

Cancer Care Ontario

Document Publication Date: Jan 6, 2026

Page Last Reviewed/Updated: May 5, 2026

Document Type: Guideline

Country of Publication: United States

Full Text Freely Available: Yes

Full Text Guideline: ascopubs.org/doi/10.1200/JCO-25-02587

Source Citation: Hicks LK, Messersmith HJ, Al Hadidi S, et al. Treatment of Multiple Myeloma: ASCO Ontario Health (Cancer Care Ontario) Living Guideline. J Clin Oncol. 2025 Jan 6. doi: 10.1200/JCO.25.02587

Supplemental Implementation Resources

Document Scope, Criteria, and Use Cases

Document Objectives: To provide evidence-based recommendations on the treatment of multiple myeloma to practicing physicians and others.

Scope: Management, Treatment

Keywords: hematologic malignancies, multiple myeloma

Target Patient Population: Patients with multiple myeloma

Target Provider Population: Medical oncologists, radiation oncologists, hematologists, surgeons, nurses, advanced practice providers, oncology pharmacists

Inclusion Criteria: Male, Female, Adolescent, Adult, Child, Older Adult

Health Care Settings: Ambulatory, Hospital, Outpatient

Intended Users: Nurse, Nurse Practitioner, Physician, Physician Assistant

Recommendation Development Processes & Methodology

PICO Questions

What criteria are used to assess eligibility for autologous stem-cell transplant (ASCT)?
What are the options for initial therapy before transplant?
What post-transplant therapy should be recommended?
What are the response goals for the transplant-eligible patient?
What are the options for initial therapy in transplant-ineligible patients?
What are the response goals following initial therapy for transplant-ineligible patients?
What factors influence choice of first relapse therapy?
How does risk status influence therapy in myeloma (newly diagnosed and relapse)?
When and how should response assessment be performed?

Supplemental Methodology Resources: Data Supplement Methodology Supplement

Number of Source Documents: 209

Includes peer/external review process?: Yes

Includes public comment process?: Yes

Methodologist involvement?: Yes

Patient involvement?: Yes

Includes multi-disciplinary group?: Yes

Includes systematic review?: Yes

Grades quality of strength of evidence?: Yes

Grades quality of strength of recommendation?: Yes

Discloses funding source?: Yes

Discloses conflicts of interest?: Yes

Includes benefits/harms analysis with recommendations?: Yes

Identifies study selection process?: Yes

Identifies study selection criteria?: Yes

Identifies methods used to evaluate and analyze the evidence?: Yes

Identifies key questions addressed by the systematic review?: Yes

Identifies search strategy?: Yes

Treatment of Multiple Myeloma

Treatment

Smoldering Multiple Myeloma

Recommendation 1.1.

Recommendation 1.2.

Recommendation 1.3.

Transplant Eligible – Evaluation of Eligibility

Recommendation 2.1.1.

Recommendation 2.1.2.

Transplant Eligible – Initial Therapy

Recommendation 2.2.1.

Recommendation 2.2.2.

Recommendation 2.2.3.

Transplant Eligible – Conditioning and Transplant

Recommendation 2.3.1.

Recommendation 2.3.2.

Recommendation 2.3.3.

Recommendation 2.3.4.

Transplant Eligible – Maintenance

Recommendation 2.4.1.

Recommendation 2.4.2.

Transplant Eligible – Measurement of Response

Recommendation 2.5.1.

Transplant Ineligible – Therapy

Recommendation 3.1.1.

Recommendation 3.1.2.

Transplant Ineligible – Goals of Therapy and Measurement of Response

Recommendation 3.2.1.

Recommendation 3.2.2.

Recommendation 3.2.3.

Relapsed/Refractory – Therapy

Recommendation 4.1.

Recommendation 4.2.

Recommendation 4.3.

Recommendation 4.4.1.

Recommendation 4.4.2.

Recommendation Rating Definitions

Document Overview

Supplemental Implementation Resources

Document Scope, Criteria, and Use Cases

Recommendation Development Processes & Methodology