2026 NCCN and ASCO​ multiple myeloma guidelines

By Litha Mfiki

What’s new in multiple myeloma management?

Two major guideline bodies released updated guidance in 2026 on the management of multiple myeloma (MM), reflecting rapidly evolving evidence across newly diagnosed, transplant‑eligible, and transplant‑ineligible settings, as well as relapsed disease. Updates from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) and the American Society of Clinical Oncology (ASCO)–Ontario Health Living Guideline clarify treatment selection, transplant use, and maintenance strategies.^1,2

Quadruplet therapy as standard initial treatment for multiple myeloma 

For patients with newly diagnosed MM, the NCCN Guidelines^® and the ASCO–Ontario Health Living Guideline recommend quadruplet regimens that combine an anti-CD38 monoclonal antibody with bortezomib, lenalidomide, and dexamethasone as the preferred initial therapy.

For transplant-eligible patients, the guidelines recommend daratumumab- or isatuximab-based quadruplet induction therapy, followed by autologous stem cell transplantation and maintenance.

For transplant-ineligible patients who are fit and able to tolerate intensive therapy, both guidelines endorse using the same anti-CD38–based quadruplet backbone as first-line treatment but emphasize the importance of frailty assessment and treatment individualization.

Clarified criteria for transplant eligibility in multiple myeloma

The ASCO–Ontario Health Living Guideline emphasizes that chronological age and renal function alone should not determine transplant eligibility in MM. Instead, clinicians should assess:

• Performance status
• Comorbidities
• Frailty

The NCCN Guidelines continue to recommend early referral to a transplant center for eligible patients and support autologous stem cell collection early in the treatment course, even if transplantation is deferred.

Refined maintenance therapy recommendations in multiple myeloma

Both the NCCN Guidelines and the ASCO–Ontario Health Living Guideline recommend lenalidomide maintenance following autologous stem cell transplantation.

The guidelines state that, in selected patients with high-risk disease, agents such as daratumumab or carfilzomib may be added to lenalidomide maintenance, although the independent contribution of maintenance intensification beyond modern quadruplet induction remains uncertain.

Treatment of smoldering multiple myeloma

The ASCO–Ontario Health Living Guideline introduces updated recommendations for high-risk smoldering MM. Daratumumab may be offered as an alternative to active monitoring in carefully selected high-risk patients, while systemic therapy is not recommended for patients who do not meet high-risk criteria. Active MM should be excluded by using contemporary diagnostic standards before initiating treatment.

Expanded guidance for relapsed or refractory multiple myeloma

For relapsed or refractory MM, both the NCCN Guidelines and the ASCO–Ontario Health Living Guideline recommend triplet therapy when feasible, incorporating agents with different mechanisms of action than prior lines of therapy.

The ASCO–Ontario Health Living Guideline outlines updated, principle-based recommendations for the use of chimeric antigen receptor (CAR) T-cell therapies and bispecific antibodies, emphasizing patient selection, disease tempo, prior treatment exposure, feasibility of manufacturing timelines, and shared decision-making rather than prescriptive sequencing.

READ MULTIPLE MYELOMA GUIDELINES

References

1. Kumar, 2026. Multiple Myeloma, Version 5.2026, NCCN Clinical Practice Guidelines In Oncology. https://www.doi.org/10.6004/jnccn.2026.0001
2. Hicks, 2026. Treatment of multiple myeloma: ASCO–Ontario Health (Cancer Care Ontario) Living Guideline. https://www.doi.org/10.1200/jco-25-02587

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