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Final analysis of phase 2 GRIFFIN study for Daratumumab-based investigational quadruplet regimen in patients with newly diagnosed, transplant-eligible multiple myeloma

Final results from the randomized phase 2 GRIFFIN study evaluating the investigational use of Daratumumab ( Darzalex ) in combination with Lenalidomide ( Revlimid ), Bortezomib ( Velcade ) and Dexamethasone ( Daratumumab-RVd ), followed by maintenance therapy with Daratumumab - Lenalidomide ( R ), compared to RVd followed by maintenance therapy with R alone, in patients with newly diagnosed, transplanteligible multiple myeloma, were presented at IMS meeting.

In the primary analysis ( median follow-up of 13.5 months ), the GRIFFIN study met its primary endpoint, resulting in a higher stringent complete response ( sCR ) rate for Daratumumab-RVd compared with RVd alone by the end of post-autologous stem cell transplant ( ASCT ) consolidation therapy ( 42.4% vs 32%; 1-sided P=0.0680 ) meeting the prespecified 1-sided alpha of 0.1.

At IMS, the predefined final analysis for GRIFFIN ( median follow-up of 49.6 months ), which occurred after all patients had completed at least one year of follow-up after end of study therapy or withdrew, showed that longer progression-free survival ( PFS ) was observed in patients who received Daratumumab-RVd / Daratumumab-R compared to those who received RVd/R ( hazard ratio. HR= 0.45; 95% confidence interval, 0.21-0.95; P=0.0324 ).
Higher minimal residual disease ( MRD ) negativity rates were observed for Daratumumab-RVd vs RVd ( 64% vs 30% ).
No new safety concerns were observed with longer-term follow-up.

After two years of maintenance therapy, the MRD negativity rate continued to favor Daratumumab-RVd versus RVd ( 64% vs 30%; P less than or equal to 0.0001 ).
Additionally, 44% of patients who received Daratumumab-RVd has achieved sustained MRD negativity lasting 12 months or more, compared to 14% of patients in the RVd arm.
Treatment with Daratumumab-RVd has also resulted in higher sCR rates at all time points in the study, with the highest rates occurring following two years of maintenance therapy ( 67% vs 48%; P=0.0079, respectively ). Complete response or better rate was 83% in the Daratumumab-RVd arm vs 60% in the RVd arm ( P=0.005 ).

At the conclusion of the final analysis, after a median follow-up of 49.6 months, a 55% reduction in the risk of disease progression or death was observed in patients in the Daratumumab-RVd arm; an estimated 48-month PFS rate of 87.2% was observed in the Daratumumab-RVd arm, compared to 70% in the RVd arm.
Median PFS was not reached in either treatment arm.
In addition, after extended follow-up, no new safety concerns were observed.

Multiple myeloma is an incurable blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow. When damaged, these plasma cells rapidly spread and replace normal cells with tumors in the bone marrow.
In 2022, it is estimated that more than 34,000 people will be diagnosed and close to 12,000 will die from the disease in the U.S.
While some patients with multiple myeloma have no symptoms, most patients are diagnosed due to symptoms, which can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems or infections. ( Xagena )

Source: 19th International Myeloma Society ( IMS ) Annual Meeting, 2022