08/05/2026

Findings From ENDURANCE Trial Offer New Standard of Care for Multiple Myeloma

Professional portrait of a middle-aged man in a black suit, white shirt, and blue tie, wearing glasses, smiling confidently against a neutral background. Shaji Kumar, MD An Indian male doctor in a suit and tie smiling, professional portrait on gray background. S. Vincent Rajkumar, MD Smiling man with beard wearing a white shirt, professional headshot, suitable for oncology or cancer research content, emphasizing healthcare and medical expertise. Rahul Gosain, MD, MBA Oncologist smiling in white coat, highlighting cancer research and treatment expertise, with a bow tie, in a bright medical setting. Rohit Gosain, MD
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Key Points

  • Results of the phase 3 ENDURANCE trial showed that fixed-duration maintenance therapy provided the same long-term survival benefit as indefinite-duration treatment in patients with standard-risk multiple myeloma.
  • These findings establish “a new standard of care” that is expected to be adopted immediately in the community oncology setting.
  • The study’s authors plan to collect more data on survival rates and outcomes for high-risk patients, including which therapeutic strategies can provide the most benefit.

On the Oncology Brothers podcast, cohosts Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, met with Vincent Rajkumar, MD, and Shaji Kumar, MD, both of Mayo Clinic, to discuss the findings and implications of the phase 3 ENDURANCE trial.

Results of the trial, published in the New England Journal of Medicine, indicate that for standard-risk patients with newly diagnosed multiple myeloma, indefinite maintenance therapy following induction therapy did not lead to significantly longer overall survival than fixed-duration maintenance therapy.

These findings establish “a new standard of care,” according to Dr. Rahul Gosain, who said he expects it to be “adopted right away” in the community oncology setting.

Potential of Limited-Duration Lenalidomide Therapy

For some time, the standard treatment for multiple myeloma has been quadruplet therapy — which includes an anti-CD38 antibody along with a proteasome inhibitor, lenalidomide, and steroids — followed by continuous lenalidomide maintenance, Dr. Rahul Gosain noted. Although this strategy has led to significant advances in survival rates over the past 2 decades, prolonged therapy has also raised concerns, particularly regarding toxicity.

The ENDURANCE trial authors sought to learn whether limited-duration therapy could yield results similar to those of continuous treatment. “We started to ask if that was really needed, or if we could give lenalidomide maintenance for a fixed duration,” Dr. Kumar said. “We have to ask these questions because it can help our patients reduce toxicity.” 

Those questions were answered. At a follow-up of 86 months, results showed no significant difference in survival rates between the indefinite-duration and fixed-duration group. Additionally, adverse events were more likely to occur in the indefinite-duration group. The authors concluded that “for standard-risk patients, 2 years [of lenalidomide therapy] is more than enough,” Dr. Kumar said.

“Trial after trial has been designed to give patients treatment until progression without necessarily exploring the alternative option,” he added. “That’s the true impact of this study.”

Minimal Residual Disease in High-Risk Patients

Another key factor in treatment decisions is minimal residual disease (MRD) status, a strong predictor of outcomes in multiple myeloma. If MRD is shown to be positive at the 2-year mark, Dr. Kumar recommended stopping treatment with lenalidomide. “We already know we’re not going to see any more deepening of response,” he said. “There are no studies showing that pushing somebody into MRD negativity after 2 years of being MRD-positive is going to change the outcome.”

For high-risk patients, he recommends assessing MRD status. “We believe getting them MRD-negative and keeping them there might give them the best chance at long-term outcomes.”

The authors plan to collect more data on overall survival and outcomes with MRD-directed therapy. “We’re not giving up on the high-risk population,” Dr. Rajkumar said. “We want to go to time-limited therapy so that we can declare a cure. You cannot declare a cure if you’re not willing to stop therapy. That’s our fundamental philosophy.”

The hope, he added, is that in a few years, “we’ll have enough data to guide high-risk patients on which drugs to stop and which combination will be the one that will provide the maximum benefit.”

Immediate Implications of ENDURANCE 

In the meantime, the ENDURANCE findings can be immediately applied in the community oncology setting, according to Dr. Rohit Gosain: “We continue to learn in the world of cancer that more is not always better; this study is evidence of that. We’ve always hoped for guidance to stop maintenance therapy. Now, we finally have data.”

Going forward, experts hope to determine whether the findings can be extrapolated to patients with multiple myeloma who don’t meet the eligibility criteria. “We have to be very careful when we go down that route,” said Dr. Rohit Gosain. For now, if a standard-risk patient undergoes transplant, lenalidomide can be stopped after the 2-year mark. “The ENDURANCE trial is a big win for our patients,” he said, “and this time-limited approach sets a new standard of care for standard-risk multiple myeloma in maintenance therapy.”