ASCO, in collaboration with Ontario Health (Cancer Care Ontario), has published an update to their previous guideline on the treatment of multiple myeloma.1 This new guideline—which has been selected as an ASCO Living Guideline—reflects dramatic changes that have helped improve the management of multiple myeloma over the past several years.
Lisa K. Hicks, MD, MSc, FRCPC
“Multiple myeloma is increasingly complex, with many, many treatment options available, and also, it’s a very rapidly moving field. This is a wonderful problem to have, and it’s fantastic for patients,” said Lisa K. Hicks, MD, MSc, FRCPC, of St. Michael’s Hospital in Toronto and co-chair of the Expert Panel that developed the Living Guideline.
Keeping Up With Changes
ASCO Living Guidelines were created to allow clinical guidance in rapidly developing areas of oncology to be updated and disseminated on a regular basis.
Guideline Co-Chair Joseph Mikhael, MD, MEd, FRCPC, FACP, FASCO, of the Translational Genomics Research Institute and the International Myeloma Foundation, noted that multiple myeloma is “the perfect example” of a disease well suited to Living Guidelines, as significant advances have occurred in the field since the original guideline was published in 2019, including two recent U.S. Food and Drug Administration approvals, in October and in November 2025.2-4
Joseph Mikhael, MD, MEd, FRCPC, FACP, FASCO
“This is a new process for ASCO, and I think it is critically important, especially in a disease where there’s such a rapidly evolving science and choice of therapies,” he said.
For instance, the previous guideline did not address the asymptomatic condition that is often a precursor to multiple myeloma, known as smoldering myeloma. Yet, its incidence and prevalence have been steadily increasing since 2010, underscoring the importance of improved detection and management.5
Dr. Hicks noted that the Expert Panel’s literature review uncovered 161 new clinical trials published since the last guideline that they needed to include.
“That just really illustrates how difficult it is for people to stay abreast of the literature and keep track of the myeloma field,” she said.
Hematologic malignancy experts representing ASCO and Ontario Health worked collaboratively on the update, as they did for the prior guideline. The Expert Panel used the GRADE method—which stands for grading of recommendations, assessment, development, and evaluation—to critically appraise the literature in a rigorous and transparent way.
“We did not want this guideline to just be expert opinion,” Dr. Mikhael said. “Our process was to take the best evidence and, in the most sophisticated way, objectively evaluate that evidence,” adding that the Expert Panel ensured the information in the guideline “was translated into clinical practice in the most pragmatic way.”
Key Recommendations
The Living Guideline makes several key recommendations. For instance, the Panel recommended all patients with smoldering myeloma receive active monitoring for up to 36 months. However, they also made a conditional recommendation for the use of daratumumab instead of active monitoring for certain high-risk individuals
Another new recommendation concerns the use of quadruplet therapy consisting of daratumumab or isatuximab in addition to bortezomib, lenalidomide, and dexamethasone as the standard of care for patients with newly diagnosed multiple myeloma.
The option of adding daratumumab or carfilzomib to lenalidomide maintenance therapy for select patients (eg, those with certain high-risk genetic abnormalities) is also a new recommendation from the previous guideline.
Finally, the Living Guideline offers novel guidance on the use of cell-redirected therapies, such as CAR T-cell therapies and bispecific antibody therapies. Specifically, the Panel recommended that eligible patients be offered CAR-T cell therapy, following discussions about its risks and benefits. However, they note that patients with rapidly progressive relapsed myeloma are not ideal candidates because of the time required to manufacture the engineered CAR T-cells.
“In this environment, it can be very challenging to select the most appropriate, evidence-based treatment for patients with myeloma,” Dr. Hicks said. “So, it is our hope that this guideline will help practitioners make sense of a rapidly moving and complicated field.”
Enhancing Patient Care
Multiple myeloma is a relatively rare cancer. For oncologists who do not specialize in myeloma and, thus, see comparatively fewer patients with this disease, it can be especially challenging to keep pace with the changes.
“Most oncologists spend about 80% of their time on the ‘big 4’—breast, lung, colon, and prostate cancers. And myeloma typically accounts for less than 5% of their work because it accounts for only 2% of cancers,” he said.
As a result, Dr. Mikhael added, community oncologists in particular, who typically see a broad range of cancers, “want something that they can easily reach to that is going to give them practical guidance.”
The Panel was also vigilant about addressing the importance of shared decision-making. For example, the Living Guideline articulates some ways that clinicians can incorporate patient preferences into treatment decisions, such as having conversations with patients about a variety of treatment-related topics and concerns, including side effects, quality of life, treatment goals, and participation in clinical trials. Making treatment decisions collaboratively with patients is important for all cancers and is not a new concept. However, it becomes even more critical when the treatment choices are so varied.
“We see in a disease like myeloma that, based on people’s background, vocation, and access to therapies, there could be huge variation in what they are treated with,” Dr. Mikhael said. “We emphasize in the guideline that often there are several choices, which is great, but making those choices should not just be based on provider opinion.”
Other topics related to patient care that the guideline addresses include treatment sequencing, especially in regard to CAR T-cell therapies, frailty, and the importance of geriatric assessments.
“There are a lot of studies ongoing, so we know this field is going to keep changing quickly, probably in the next 6 to 12 months,” Dr. Hicks added. “We want as many patients with myeloma as possible to benefit from the amazing advances that have occurred in this field.”
REFERENCES
1. Hicks LK, et al: Treatment of multiple myeloma: ASCO-Ontario Health (Cancer Care Ontario) Living Guideline. J Clin Oncol. Published online January 6, 2026.
2. Mikhael J, et al: Treatment of multiple myeloma: ASCO and CCO Joint Clinical Practice Guideline. J Clin Oncol 37:1228-1263, 2019.
3. U.S. Food and Drug Administration. FDA approves belantamab mafodotin-blmf for relapsed or refractory multiple myeloma. October 23, 2025.
4. U.S. FDA: FDA approves daratumumab and hyaluronidase-fihj for high-risk smoldering multiple myeloma. November 6, 2025.
5. Wong A, et al. Blood Cancer J 15:149, 2025.
Originally published in ASCO Daily News. © American Society of Clinical Oncology. January 6, 2026. All rights reserved.
