myeloma

Daratumumab, Lenalidomide, Bortezomib, And Dexamethasone For Transplant-Eligible Newly Diagnosed Multiple Myeloma: The GRIFFIN Trial

Daratumumab, Lenalidomide, Bortezomib, And Dexamethasone For Transplant-Eligible Newly Diagnosed Multiple Myeloma: The GRIFFIN Trial

In the August 20, 2020 addition of the journal Blood, investigators reported on the utility of the addition of daratumumab to a combination of lenalidomide, bortezomib and dexamethasone as induction prior to autologous stem cell transplantation for newly diagnosed patients with multiple myeloma.  

207 patients were randomized in a one-to-one fashion to daratumumab plus lenalidomide, bortezomib, dexamethasone or the triplet regimen without daratumumab.  Patients were given 4 cycles of induction, followed by autologous stem cell transplantation, followed by 2 cycles of consolidation with the same therapy.  26 cycles of maintenance with lenalidomide plus dexamethasone followed the induction and consolidation phase. The primary endpoint was a stringent complete response rate by the end of post autologous stem cell transplant consolidation, which favored the quadruplet regimen, 42.4% versus 32%, odds ratio 1.57, 95% confidence interval 0.87–2.82, one-sided P value of 0.068. It met the prespecified 1 side alpha of 0.10.  After a long follow-up, median of 22.1 months, responses were deepened, with a stringent complete response rate improved for the quadruplet regimen of 62.6% versus 45.4%, P value of 0.0177.  

Minimal residual disease negativity, defined as a 1/100,000 threshold, rates in the intent to treat population, 51% versus 20.4%, P < 0.0001.  3.8% of patients, n=4 patients, in the quadruplet regimen, and 6.8% of patients, n=7 patients, in the triplet regimen, progressed.  The 24-month progression free survival rates were 95.8% and 89.8% for the quadruplet and triplet regimen, respectively.  Grade 3 and 4 hematologic adverse events were notable in the quadruplet regimen.  More infections occurred in the quadruplet regimen but grade 3 and 4 infection rates were similar.  The authors noted that plerixafor utilization was more common in the quadruplet regimen, because of a slight decrease in the median CD34 positive cell yield, 8.2 versus 9.4 million cells / kg.  The median time to neutrophil and platelet engraftment were comparable.  

The authors concluded “daratumumab with lenalidomide, bortezomib, dexamethasone induction and consolidation improved depth of response in patients with transplant eligible newly diagnosed multiple myeloma, with no new safety concerns.”

https://ashpublications.org/Blood/article/136/8/936/454474/Daratumumab-lenalidomide-bortezomib-and

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