In Final CEPHEUS Analysis for Myeloma, Median PFS Not Reached After More Than 6 Years

After more than 6 years of follow-up, the final analysis from the phase 3 CEPHEUS trial has affirmed the quadruplet of daratumumab (Darzalex; Johnson & Johnson) plus bortezomib (Velcade; Johnson & Johnson), lenalidomide (Revlimid; Bristol Myers Squibb), and dexamethasone (DVRd) as the standard of care for transplant-ineligible patients with newly diagnosed multiple myeloma.¹

At Sunday’s hematology session at the annual meeting of the American Society of Clinical Oncology (ASCO), lead investigator Saad Z. Usmani, MD, MBA, FASCO, of Memorial Sloan Kettering Cancer Center, shared a statistic rarely seen: the trial will close with the median progression-free survival (PFS) not reached.

“Nearly 60% of the patients remain alive and progression-free at 72 months with DVRd, with a median PFS not being reached, which is quite remarkable for this patient population,” Usmani said, reminding the audience that most of the patients in the trial were ineligible for autologous stem cell transplant.

CEPHEUS is a randomized, open-label trial that evaluated the addition of subcutaneous daratumumab (Darzalex Faspro) to standard-of-care VRd for patients with newly diagnosed multiple myeloma who are transplant ineligible or have deferred a transplant. The final analysis focused on the 289 transplant-ineligible patients who made up roughly 75% of the 395 enrolled in CEPHEUS.² These patients, with a median age of 72 and approximately 30% aged 75 or older, are precisely the group for whom durable disease control matters most. Study patients will continue to have access to therapy after the trial ends.

Usmani reviewed the final PFS data: At 72 months, 59.3% of patients treated with DVRd remained alive and progression-free, compared with 38.3% of those in the VRd arm. Again, median PFS for the DVRd group was not reached (95% CI, 74.81 months–not estimable), whereas the median PFS on VRd was 50.2 months. This translates to a 45% reduction in the risk of disease progression or death (HR, 0.55; 95% CI, 0.39-0.78; P = .0007).¹

The survival results were accompanied by the depth and durability of the responses, as measured by minimal residual disease (MRD) negativity. The overall MRD-negativity rate at the 10^–5 threshold was 61.1% for DVRd versus 40.0% for VRd (OR, 2.35; P = .0004), and at the more stringent 10^–6 threshold, 46.5% vs 27.6% (OR, 2.27; P = .0010).

Usmani explained that these deep responses held up over time. The sustained MRD-negativity rate beyond 12 months at 10^–5 was 49.3% with DVRd vs 29.0% with VRd, and sustained negativity at the 10^–6 level reached 37.5% vs 16.6% (OR, 3.01; P < .0001).

“With this post hoc analysis, we focused on these primary end points for this transplant-inelegible patient population, showing overall MRD negativity being superior for 10^–5 and 10^–6 thresholds, and then the 12-month and 24-month sustained MRD negativity rates show the same pattern,” he said.

The overall complete response or better rate was 80.6% with DVRd compared to 61.4% with VRd. On overall survival, DVRd showed a favorable trend (HR, 0.84), which became more pronounced when deaths attributable to COVID-19 were censored (HR, 0.74). Usmani reminded the audience that the trial enrolled at the height of the pandemic before vaccinations were available, a confounding factor that affected both arms and likely blunted the overall survival signal.

No new safety concerns emerged with extended follow-up in this older patient population, reinforcing the tolerability of the regimen in a group that demands careful attention to toxicity.

“These data continue to reinforce DVRd as a standard of care in the transplant-ineligible [newly diagnosed multiple myeloma] population,” the investigators concluded.

References

1. Usmani SZ, Facon T, Hungria V, et al. Daratumumab plus bortezomib, lenalidomide, and dexamethasone (DVRd) in patients (pts) with newly diagnosed multiple myeloma (NDMM): final analysis of transplant-ineligible (TIE) pts in the phase 3 CEPHEUS study. J Clin Oncol. 2026;44 (suppl 16):Abstr 7513. doi:10.1200/JCO.2026.44.16_suppl.7513
2. Caffrey M. CEPHEUS: sub-Q daratumumab with VRd improves MRD negativity, PFS in myeloma if transplant deferred. AJMC^®. September 27, 2024. Accessed June 1, 2026. https://www.ajmc.com/view/cepheus-sub-q-daratumumab-with-vrd-improves-mrd-negativity-pfs-in-myeloma-if-transplant-deferred