FDA Receives sNDA for Daratumumab Combo in Newly Diagnosed Multiple Myeloma

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Findings from the phase 3 PERSEUS trial support the supplemental New Drug Application for the daratumumab and hyaluronidase-fihj combination in transplant-eligible newly diagnosed multiple myeloma.

Supporting data for the sNDA in this indication came from the phase 3 PERSEUS trial (NCT03710603).

Supporting data for the sNDA in this indication came from the phase 3 PERSEUS trial (NCT03710603).

Developers have submitted a supplemental new drug application (sNDA) for daratumumab and hyaluronidase-fihj (Darzalex Faspro) in combination with lenalidomide (Revlimid) plus bortezomib (Velcade) and dexamethasone (D-VRd) followed by lenalidomide maintenance for adult patients with transplant-eligible newly diagnosed multiple myeloma, according to a press release from Johnson & Johnson.1

Supporting data for the sBLA in this indication came from the phase 3 PERSEUS trial (NCT03710603). According to data published in New England Journal of Medicine, the estimated 48-month progression-free survival (PFS) rate was 84.3% (95% CI, 79.5%-88.1%) in those who received D-VRd vs 67.7% (95% CI, 62.2%-72.6%) among those who were treated with VRd (HR, 0.42; 95% CI, 0.30-0.59; P <.001).2 Additionally, a complete response (CR) or better was reported in 87.9% and 70.1% of patients in each respective arm (P <.001), and the rates of minimal residual disease (MRD) negativity were 75.2% vs 47.5% (P <.001), respectively.

Investigators highlighted that the safety profile of D-VRd plus lenalidomide maintenance was comparable with prior reports for each individual agent. Common grade 3/4 adverse effects (AEs) in the D-VRd and VRd arms, respectively, included neutropenia (62.1% vs 51.0%), thrombocytopenia (29.1% vs 17.3%), diarrhea (10.5% vs 7.8%), pneumonia (10.5% vs 6.1%), and febrile neutropenia (9.4% vs 10.1%). Additionally, 8.8% and 21.3% of patients in each respective arm experienced AEs leading to treatment discontinuation.

“We are committed to changing the course of multiple myeloma through building combination regimens such as D-VRd with complementary mechanisms of action,” Craig Tendler MD, vice president of Clinical Development, Diagnostics, and Global Medical Affairs at Johnson & Johnson Innovative Medicine, said in the press release.1

“The [daratumumab and hyaluronidase-fihj]–based quadruplet therapy demonstrated a clinically significant reduction in the risk of progression or death for transplant-eligible, newly diagnosed patients with multiple myeloma. Patients are most likely to experience their deepest and most durable responses during the first line of treatment with D-VRd. This regimen has the potential to improve long-term outcomes for newly diagnosed patients and we look forward to working with the FDA on the review of this application.”

In the ongoing, open-label PERSEUS trial, 709 patients were randomly assigned 1:1 to receive subcutaneous daratumumab plus VRd induction before transplantation plus VRd consolidation and maintenance lenalidomide (n = 355) or VRd induction and consolidation plus maintenance lenalidomide only (n = 354).

The trial’s primary end point was PFS. Secondary end points included the CR or better rate, MRD negativity in those with a CR or better, and overall survival.

Patients 18 to 70 years old with monoclonal plasma cells in at least 10% of the bone marrow or plasmacytoma and documented multiple myeloma were able to enroll on the trial. Additional inclusion criteria included having adequate bone marrow, liver, and renal function.

Those who had prior systemic therapy or stem cell transplant for any plasma cell dyscrasia, radiotherapy within 2 weeks of randomization, or plasmapheresis within 4 weeks of randomization were unable to enroll on the trial.

References

  1. Johnson & Johnson submits supplemental biologics license application to U.S. FDA seeking approval of DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj)-based regimen for the treatment of patients with transplant-eligible, newly diagnosed multiple myeloma. News release. Johnson & Johnson. January 30, 2024. Accessed January 31, 2024. http://tinyurl.com/y9ck33d5
  2. Sonneveld P, Dimopoulos MA, Boccadoro M, et al. Daratumumab, bortezomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. Published online December 12, 2023. doi:10.1056/NEJMoa2312054
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