Study demonstrates a minimal residual disease (MRD)-negativity rate of 60.9 percent and 43 percent reduction in the risk of progression or death¹

Phase 3 CEPHEUS study results presented in late-breaking oral presentation at the International Myeloma Society (IMS) Annual Meeting¹

Janssen-Cilag International NV, a Johnson & Johnson company, announced results from the Phase 3 CEPHEUS study demonstrating a significant clinical improvement with DARZALEX^® (daratumumab) subcutaneous (SC) formulation in combination with bortezomib, lenalidomide and dexamethasone (D-VRd) in the treatment of patients with newly diagnosed multiple myeloma (NDMM) who are transplant ineligible (TIE) or for whom transplant was not planned as initial therapy (transplant deferred).¹ The data showing significant improvement in minimal residual disease (MRD)-negativity rate, progression-free survival (PFS) and complete response (CR) or better rate, were featured as a late-breaking oral presentation at the 21^st International Myeloma Society (IMS) Annual Meeting, taking place in Rio de Janeiro, Brazil, from 25-28 September (Abstract #LBA OA-63).¹

“The CEPHEUS study results show that 60 percent of patients achieved MRD-negativity, which is clinically important for physicians treating people with multiple myeloma and, in general, a strong predictor of improved long-term outcomes, including progression-free survival and overall survival,” said Saad Z. Usmani, M.D., F.A.C.P., Chief, Myeloma Service, Memorial Sloan Kettering Cancer Center and Study Investigator.* “The subcutaneous daratumumab-based quadruplet regimen has compelling efficacy characterised by deep, durable responses and reduced risk of disease progression in the frontline population of patients not undergoing transplant, supporting the potential of this quadruplet to become a new regimen in this treatment setting.”

CEPHEUS is an ongoing, multicentre, randomised, open-label, Phase 3 study evaluating the efficacy and safety of D-VRd compared to bortezomib, lenalidomide and dexamethasone (VRd) for NDMM patients who are TIE or transplant deferred.¹ Results show that treatment with D-VRd resulted in deeper responses, including MRD-negativity, compared with VRd.¹ At a median follow-up of 58.7 months, the primary endpoint was met, with overall MRD-negativity rate at a sensitivity of 10^-5 (no cancer cells detected within 100,000 bone marrow cells) of 60.9 percent for patients receiving D-VRd and 39.4 percent for VRd (Odds ratio [OR], 2.37; 95 percent confidence interval [CI], 1.58-3.55; p<0.0001).¹ The proportion of patients achieving sustained MRD-negativity of ≥ 12 months almost doubled with D-VRd vs VRd (48.7 percent vs 26.3 percent; OR, 2.63; 95 percent CI, 1.73-4.00; p<0.0001).¹ The study also demonstrated that D-VRd significantly reduced the risk of progression or death by 43 percent (Hazard ratio [HR], 0.57; 95 percent CI, 0.41-0.79; p<0.0005) vs VRd.¹ The median PFS was not reached for D-VRd vs 52.6 months for VRd.¹

“Multiple myeloma is a complex disease and early intervention with treatment regimens that are well tolerated, effective and long-lasting is crucial to achieve the best outcomes for patients,” said Edmond Chan, MBChB, M.D. (Res), EMEA Therapeutic Area Lead Haematology, Innovative Medicine, Johnson & Johnson. “Today’s data for this daratumumab-based quadruplet regimen complements data from the PERSEUS study to reinforce our unwavering commitment to deliver innovative approaches that have the potential to make a significant impact for every person with multiple myeloma from the first line of treatment, irrespective of transplant suitability.” 

The daratumumab SC-based quadruplet regimen, compared to VRd, also significantly increased the depth of response with higher rates of CR or better.¹ The CR or better rate was 81.2 percent with D-VRd vs 61.6 percent with VRd (OR 2.73; 95 percent CI, 1.71-4.34; p<0.0001).¹ Overall survival data are not yet mature.¹ The overall safety profile of D-VRd was consistent with the known safety profiles for daratumumab SC and VRd.¹ The most common (>10 percent) Grade 3/4 haematologic and non-haematologic adverse events with D-VRd vs VRd were neutropenia (44.2 percent vs 29.7 percent), thrombocytopenia (28.4 percent vs 20.0 percent), anaemia (13.2 percent vs 11.8 percent), peripheral neuropathies (8.1 percent vs 8.2 percent), diarrhoea (12.2 percent vs 9.2 percent), and COVID-19 (11.2 percent vs 4.6 percent).¹

“Data from PERSEUS and now CEPHEUS add to the body of evidence illustrating how the daratumumab-based quadruplet regimen has the potential to be a foundational frontline therapy across all patient types during first-line treatment, regardless of transplant eligibility status,” said Robin Carson, M.D., Global Head, Oncology, Innovative Medicine, Johnson & Johnson. “We look forward to continuing to advance this potential new quadruplet therapy and deliver on our commitment to transforming outcomes for people with multiple myeloma.”