Sunday, December 3, 2023
Home News Daratumumab Plus KRd With Tandem Transplant Sustains Efficacy in High-Risk, Newly Diagnosed Myeloma

Daratumumab Plus KRd With Tandem Transplant Sustains Efficacy in High-Risk, Newly Diagnosed Myeloma

by Hayley Virgil
0 comment

Induction daratumumab (Darzalex), carfilzomib (Kyprolis), lenalidomide (Revlimid), and dexamethasone (Dara-KRd) followed by consolidation double transplant sustained efficacy and safety in patients with high-risk, newly diagnosed multiple myeloma, according to final results phase 2 IFM 2018-04 study (NCT03606577) presented at the 2023 International Myeloma Society Annual Meeting.

The complete response (CR) rate/stringent CR rate after the second autologous stem cell transplant (ASCT) was 81%, according to the per protocol analysis. Additionally, the minimal residual disease (MRD) negativity rate at the same time point was 94%.

Lead author Cyrille Touzeau, MD, PhD, a hematologist in the Department of Hematology at the University Hospital of Nantes, Frances noted that response rates continuously improved during the study.

Touzeau also reported that the progression-free survival (PFS) rate was 86% (95% CI, 77%-97%) at 24 months and 80% (95% CI, 68%-94%) at 30 months. Additionally, the 24-month and 30-month overall survival (OS) rates were 94% (95% CI, 87%-100%) and 91% (95% CI, 82%-100%), respectively. In total, 8 patients progressed, and 7 died due to both disease progression (n = 5) and serious adverse effects (SAEs; n = 2).

“Dara-KRd plus double transplant induced deep response rates and a high MRD negativity rate,” Touzeau said during a presentation on the findings. “…These favorable results are in accordance with the GMMG CONCEPT trial [NCT03104842] for our German Colleagues. The safety and efficacy profile of anti-CD38/KRd plus double transplant support this intensive approach for high-risk patients based on MRD positivity in our IFM phase 3 MIDAS trial [NCT04934475].”

The trial included patients who were under 66 years old with newly diagnosed, transplant-eligible multiple myeloma that is high risk with an ECOG performance status of 0 to 2. The trial’s primary end point was getting over 70% of patients to second transplant, with key secondary end points including safety, overall response rate, PFS, OS, and stem cell collection.

Patients were treated with 16 mg/kg of daratumumab intravenously on days 1, 8, 15, and 22 of cycles 1 and 2 followed by days 1 and 15 during cycles 3 to 6. This was followed by 36 mg/m2 of carfilzomib intravenously on days 1 to 2, 8 to 9, and 15 to 16; 25 mg of lenalidomide on days 1 to 21; and 20 mg or dexamethasone on days 1 to 2, 15 to 16, and 22 to 23. After first transplant, patients received 16 mg/kg of daratumumab on days 1 and 15; 56 mg/m2 of carfilzomib on days 1, 8, and 15; 15 mg of lenalidomide on days 1 to 21; and 40 mg of dexamethasone on days 1, 8, 15, and 22. This was followed by the second transplant and 2 years of maintenance treatment with 16 mg/kg of daratumumab every 8 weeks and 10 mg of lenalidomide.

The median patient age was 57 years (range, 38-65). A total of 8% of patients had extramedullary disease, and all patients had high-risk cytogenetics, including del(17p; 40%), t(4;14; 52%), and t(14;16; 20%). Additionally, 60% of patients had 2 or more high-risk cytogenetic abnormalities.

As of this update, 56% of patients were receiving ongoing treatment, and 42% had discontinued due to stem cell collection failure (n = 8), progressive disease (n = 8), AEs (n = 4), and withdrawal (n = 1). Although stem cell collection originally took place after cycle 6, the study protocol was later amended to take place after cycle 3. It was reported that 16% of patients were unable to proceed to tandem transplant because of insufficient stem cell collection.

In terms of hematologic AEs, common any-grade events included neutropenia (48%), anemia (34%), and thrombocytopenia (36%); these were also the most common grade 3/4 events (44%, 22%, and 24%, respectively). Frequent any-grade non-hematologic AEs were infection (64%), gastrointestinal (GI) disorders (62%), and peripheral neuropathy (20%), with grade 3/4 AEs including infection (14%) and GI disorders (10%).


Touzeau C, Perrot A, Hulin C, et al. Daratumumab, carfilzomib, lenalidomide, and dexamethasone with tandem transplant in high-risk newly diagnosed myeloma patients: final results of the phase 2 study IFM 2018-04. 2023 International Myeloma Society Annual Meeting; September 27-30, 2023; Athens, Greece. Abstract OA-54.

Article Source link

You may also like

Leave a Comment

About Us

Welcome to Transplant news, your trusted source for the latest updates, stories, and information on transplantation and organ donations. We are passionate about sharing the inspiring journeys, groundbreaking research, and invaluable resources surrounding the world of transplantation.

Copyright ©️ 2023 Transplant News | All rights reserved.