FDA News

FDA approves Darzalex for newly diagnosed, transplant-ineligible multiple myeloma

The FDA expanded the approval of daratumumab for use in combination with bortezomib, melphalan and prednisone to include the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant, according to the agent’s manufacturer.

Daratumumab (Darzalex, Janssen) is a CD38-directed antibody.

The FDA based this expanded approval on data from the phase 3 ALCYONE study — published in The New England Journal of Medicine — of 706 patients with newly diagnosed multiple myeloma who were ineligible for stem cell transplantation. Researchers randomly assigned patients to receive either bortezomib (Velcade, Takeda/Millennium), melphalan and prednisone — a combination known as VMP — or daratumumab plus VMP.

Daratumumab plus VMP reduced the risk for disease progression or death by 50% compared with VMP alone (HR = 0.5; 95% CI, 0.38-0.65).

Median PFS was not reached in the daratumumab combination arm compared with 18.1 months in the control arm.

Treatment with daratumumab plus VMP also significantly improved overall response rates compared with VMP alone (91% vs. 74%). Eighteen percent of patients treated with the daratumumab combination achieved a stringent complete response (vs. 7% for VMP alone), 43% achieved a complete response or better (vs. 50%), and 71% achieved a very good partial response or better (vs. 24%).

A greater proportion of patients who received daratumumab in combination with VMP achieved minimal residual disease negativity (22% vs. 6%).

“This approval is significant as we now have the first antibody-based regimen for treating newly diagnosed multiple myeloma patients who are not eligible for a stem cell transplant,” Andrzej Jakubowiak, MD, PhD, director of the multiple myeloma program at University of Chicago Medical Center, said in a company-issued press release. “In clinical studies, patients who received treatment with daratumumab experienced a lower risk of disease progression and higher rates of response.”

The most common adverse events associated with daratumumab plus VMP included upper respiratory tract infection (48%), infusion reactions (28%) and peripheral edema (21%). Serious adverse reactions in the daratumumab combination arm included pneumonia (11%), upper respiratory tract infection (5%) and pulmonary edema (2%). The most common grade 3 or grade 4 treatment-emergent hematology laboratory abnormalities associated with treatment with daratumumab plus VMP included lymphopenia (58%), neutropenia (44%) and thrombocytopenia (38%).

Daratumumab also is indicated:

  • as a monotherapy for patients with multiple myeloma who have received at least three prior lines of therapy;
  • in combination with lenalidomide (Revlimid, Celgene) and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy; and
  • in combination with pomalidomide (Pomalyst, Celgene) and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies.

“Slowing the progression of myeloma translates to more time in remission for those battling the disease. This latest approval for Darzalex in combination with VMP is an exciting step forward for newly diagnosed patients and the health care teams who treat them,” Paul Giusti, president and CEO of the Multiple Myeloma Research Foundation, said in the release.

 

The FDA expanded the approval of daratumumab for use in combination with bortezomib, melphalan and prednisone to include the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant, according to the agent’s manufacturer.

Daratumumab (Darzalex, Janssen) is a CD38-directed antibody.

The FDA based this expanded approval on data from the phase 3 ALCYONE study — published in The New England Journal of Medicine — of 706 patients with newly diagnosed multiple myeloma who were ineligible for stem cell transplantation. Researchers randomly assigned patients to receive either bortezomib (Velcade, Takeda/Millennium), melphalan and prednisone — a combination known as VMP — or daratumumab plus VMP.

Daratumumab plus VMP reduced the risk for disease progression or death by 50% compared with VMP alone (HR = 0.5; 95% CI, 0.38-0.65).

Median PFS was not reached in the daratumumab combination arm compared with 18.1 months in the control arm.

Treatment with daratumumab plus VMP also significantly improved overall response rates compared with VMP alone (91% vs. 74%). Eighteen percent of patients treated with the daratumumab combination achieved a stringent complete response (vs. 7% for VMP alone), 43% achieved a complete response or better (vs. 50%), and 71% achieved a very good partial response or better (vs. 24%).

A greater proportion of patients who received daratumumab in combination with VMP achieved minimal residual disease negativity (22% vs. 6%).

“This approval is significant as we now have the first antibody-based regimen for treating newly diagnosed multiple myeloma patients who are not eligible for a stem cell transplant,” Andrzej Jakubowiak, MD, PhD, director of the multiple myeloma program at University of Chicago Medical Center, said in a company-issued press release. “In clinical studies, patients who received treatment with daratumumab experienced a lower risk of disease progression and higher rates of response.”

The most common adverse events associated with daratumumab plus VMP included upper respiratory tract infection (48%), infusion reactions (28%) and peripheral edema (21%). Serious adverse reactions in the daratumumab combination arm included pneumonia (11%), upper respiratory tract infection (5%) and pulmonary edema (2%). The most common grade 3 or grade 4 treatment-emergent hematology laboratory abnormalities associated with treatment with daratumumab plus VMP included lymphopenia (58%), neutropenia (44%) and thrombocytopenia (38%).

Daratumumab also is indicated:

  • as a monotherapy for patients with multiple myeloma who have received at least three prior lines of therapy;
  • in combination with lenalidomide (Revlimid, Celgene) and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy; and
  • in combination with pomalidomide (Pomalyst, Celgene) and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies.

“Slowing the progression of myeloma translates to more time in remission for those battling the disease. This latest approval for Darzalex in combination with VMP is an exciting step forward for newly diagnosed patients and the health care teams who treat them,” Paul Giusti, president and CEO of the Multiple Myeloma Research Foundation, said in the release.

 

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