FDA Approves Subcutaneous Daratumumab Plus Carfilzomib/Dexamethasone for Relapsed/Refractory Myeloma

The FDA has approved daratumumab and hyaluronidase-fihj plus carfilzomib and dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy.

The FDA has approved daratumumab and hyaluronidase-fihj (Darzalex Faspro) plus carfilzomib (Kyprolis) and dexamethasone (Kd) for the treatment of adult patients with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy.1,2

The regulatory decision is supported by data from the phase 3 PLEIADES trial (NCT03412565), which showed that the combination produced response rates that were similar to those reported with intravenous daratumumab (Darzalex) plus Kd in the phase 3 CANDOR study (NCT03158688).

Results showed that at a median follow-up of 9.2 months, the novel regimen elicited an overall response rate of 84.8% (95% CI, 73.9%-92.5%), meeting the primary end point of PLEIADES. Data also demonstrated that 77.3% of patients who received the combination achieved a very good partial response (VGPR) or better.

Moreover, the median duration of response with the regimen had not yet been reached and an estimated 85.2% (95% CI, 72.5%-92.3%) of patients continued to respond to treatment for at least 6 months; an estimated 82.5% (95% CI, 68.9%-90.6%) of patients maintained response for at least 9 months.

"Data from the PLEIADES trial continue to support additional treatment combinations that can influence the course of this disease as early as after the first relapse by providing durable responses that may help to delay progression," Ajai Chari, MD, professor of medicine, director of Clinical Research in the Multiple Myeloma Program, and associate director of Clinical Research in the Mount Sinai Cancer Clinical Trials Office, stated in a press release. "The approval of subcutaneous daratumumab in combination with Kd will help clinicians address unmet patient needs by reducing the administration time from hours to just minutes, and reducing the frequency of infusion-related reactions, as compared to the intravenous daratumumab formulation in combination with Kd."

The open-label, multicenter PLEIADES trial enrolled 66 patients with relapsed or refractory multiple myeloma who received at least 1 prior line of treatment. Patients with left ventricular ejection fraction of less than 40%, who had myocardial infarction within 6 months, uncontrolled cardiac arrhythmia, or uncontrolled hypertension, were excluded.3

Study participants were administered daratumumab/hyaluronidase-fihj subcutaneously at a dose of 1800 mg/30,000 units once weekly from weeks 1 to 8, once every 2 weeks from weeks 9 to 24, and once every 4 weeks starting with week 25. This formulation was combined with carfilzomib, which was given at a once-weekly dose of 20 mg/m2 on cycle 1 day 1, and if tolerated, a dose of 70 mg/m2 on cycle 1 day 8 and day 15, and then day 1, 8, and 15 of each cycle, plus dexamethasone at a weekly dose of 40 mg. Treatment was given until progressive disease or intolerable toxicity.

The median age of patients who received treatment was 61 years (range, 42-84). Fifty-two percent of patients were male, 73% were White, and 3% were Black or African American. Moreover, 68% of patients had International Staging System I disease, 18% had stage II disease, and 14% had stage III disease. Seventy-nine percent of patients previously underwent autologous stem cell transplantation, and 91% previously received a proteasome inhibitor. All participants received 1 prior line of therapy and had exposure to lenalidomide (Revlimid); 62% were refractory to lenalidomide.

Additional findings showed that of the 56 patients who responded to the regimen, 16.7% had a stringent complete response, 21.2% had a complete response, 29.4% had a VGPR, and 7.6% achieved a partial response.

Regarding safety, 77% of patients were exposed to the regimen for 6 months or longer and 27% were exposed for longer than 1 year. Twenty-seven percent of patients experienced serious adverse reactions to the treatment, and fatal adverse reactions occurred in 3% of patients. Six percent of patients discontinued the combination because of toxicity, and 46% required dose interruptions because of an adverse effect (AE).

The most commonly reported AEs included upper respiratory tract infection (all grade, 52%), fatigue (all grade, 39%; grade 3 or higher, 2%), insomnia (all grade, 33%; grade 3 or higher, 6%), hypertension (all grade, 32%; grade 3 or higher, 21%), diarrhea (all grade, 29%), cough (all grade, 24%), dyspnea (all grade, 23%; grade 3 or higher, 2%), headache (all grade, 23%), pyrexia (all grade, 21%; grade 3 or higher, 2%), nausea (all grade, 21%), and peripheral edema (all grade, 20%).

"Today's approval of DARZALEX FASPRO, in combination with yet another widely used regimen, further substantiates the subcutaneous formulation as a foundational element in the treatment of multiple myeloma," Craig Tendler, MD, global head of Late Development, Diagnostics & Medical Affairs, Hematology & Oncology, Janssen Research & Development, LLC, stated in the release. "We will continue to explore the full potential of DARZALEX FASPRO as part of our commitment to advancing science and transforming patient outcomes in the treatment of this disease."


  1. FDA approves Darzalex Faspro, Kyprolis, and dexamethasone for multiple myeloma. News release. FDA; November 30, 2021. Accessed December 1, 2021. https://bit.ly/3rr7zUF
  2. US FDA approves DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) in combination with carfilzomib and dexamethasone for patients with multiple myeloma after first or subsequent relapse. News release. The Janssen Pharmaceutical Companies of Johnson & Johnson; December 1, 2021. Accessed December 1, 2021. https://prn.to/3plTXrl
  3. Darzalex Faspro. Prescribing information. Janssen Pharmaceutical Companies; 2021. Accessed December 1, 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761145s009lbl.pdf