Janssen’s Darzalex Quadruplet for Multiple Myeloma Meets Primary Endpoint

Janssen Pharmaceutical Companies of Johnson & Johnson announced the final results from the randomized phase 2 GRIFFIN (NCT02874742)study, evaluating daratumumab (Darzalex) in combination with lenalidomide (Revlimid; Bristol-Myers Squibb), bortezomib (Velcade; Takeda Pharmaceuticals), and dexamethasone (RVd) in individuals with newly diagnosed, transplant-eligible multiple myeloma.

The drug combination was followed by maintenance therapy with Darzalex-lenalidomide (R) compared with RVd followed by maintenance therapy with R alone.

“The final analysis of the GRIFFIN trial highlights the potential benefit of adding daratumumab to RVd for the treatment of newly diagnosed, transplant-eligible patients,” Douglas Sborov, MD, MS, director of the Multiple Myeloma Program at the Huntsman Cancer Institute at the University of Utah, said in a statement.

The data were presented in the plenary session at the 19th International Myeloma Society Annual Meeting.

In the primary analysis, with a median follow up of 13.5 months, the GRIFFIN study met its primary endpoint, resulting in a higher stringent complete response (sCR) rate for Darzalex-RVd compared with RVd alone at the end of the post-autologous stem cell transplant consolidation therapy at 42.4% and 32%, respectively.

These results met the prespecified 1-sided alpha of 0.1.

At the meeting, the predefined final analysis for the study demonstrated that longer progression-free survival (PFS) was observed in individuals who received Darzalex-RVd/Darzalex-R compared with those who received RVd/R. There was a median of 49.6 months of follow up occurring after all the individuals completed at least 1 year of follow up after ending the therapy or withdrew.

There were higher minimal residual disease (MRD) negativity rates for Darzalex-RVd at 64% compared with RVd at 30%, investigators said.

There were no new safety concerns observed with the longer term follow up.

“The phase 2 GRIFFIN study showed important results with the investigational Darzalex quadruplet regimen in the treatment of newly diagnosed, transplant-eligible multiple myeloma,” Imran Khan, MD, PhD, US vice president of Medical Affairs and Hematology at Janssen Scientific Affairs, LLC, said in the statement.

“The evaluation of this treatment regimen will continue as part of the registrational, phase 3 PERSEUS [NCT03710603] study. These studies represent our ongoing focus in multiple myeloma and our commitment to advance research and new therapeutic combinations for patients at each stage of their treatment journey,” Khan said.

Additionally, 44% of individuals who received Darzalex-RVd achieved sustained MRD negativity lasting 12 months or more compared with 14% in the RVd arm. Treatment with Darzalex-RVd also resulted in higher sCR rates at all time points in the study, with the highest rates occurring following the 2 years of maintenance therapy at 67% and 48%, respectively.

The complete response or better rate was 83% with Darzalex-RVd and 60% with RVd.

Furthermore, investigators observed a 55% reduction in the risk of disease progression or death in individuals in the Darzalex-RVd arm. The estimated 48-month PFS rate was 87.2% in the Darzalex-RVd arm compared with 70% in the RVd arm. Median PFS was not reached in either arm.

There were no new safety concerns observed in the extended follow-up.

Reference

Final analysis of phase 2 GRIFFIN study presented for Darzalex (daratumumab_-based investigational quadruplet regimen in patients with newly diagnosed, transplant-eligible multiple myeloma. News release. Johnson & Johnson. August 27, 2022. Accessed August 29, 2022. https://www.jnj.com/final-analysis-of-phase-2-griffin-study-presented-for-darzalex-daratumumab-based-investigational-quadruplet-regimen-in-patients-with-newly-diagnosed-transplant-eligible-multiple-myeloma