Real World Analysis of the Efficacy, Prognosis and Safety of Daratumumab, Carfilzomib, and Dexamethasone (DKD) in Relapsed or Refractory Multiple Myeloma Patients
Authors: Fu Chengcheng , You Hongying , Jin Song , Wang Panfeng , Yan Lingzhi , Zhang Liying , Lu Tingting , Gao Xiao , Jiang Lei , Qiu Hongchun , Shang Jingjing , Zhai Yingying , Yao Weiqin , Yan Shuang , Yan Zhi , Wu Depei 
Published: December 2024

Background：
Currently patients with multiple myeloma still cannot be cured, so recurrence is inevitable. There is no uniform treatment protocol for relapsed or refractory multiple myeloma (RRMM) patients in China. The combination of DKD has been reported as a great treatment option for RRMM patients with better efficacy and PFS data and is prioritized by both domestic and foreign guidelines as a treatment option for those patients. But data on actual use in China are scarce, it is necessary to explore the efficacy and safety data of various treatment options in Chinese patients.
Methods：
This study retrospectively reported clinical data of 45 RRMM patients who were admitted to 7 centers in Suzhou area from January 2022 to May 2024. The aim was to investigate the efficacy and safety of DKD regimen for RRMM patients. The primary endpoint is ORR, and the secondary endpoints are PFS, OS, efficacy of different treatment lines subgroups, MRD negativity rate (10-5), distribution and proportion of patients with different doses of carfilzomib, and AEs.
Results：
This study included 45 patients, with a male to female ratio of 1.25:1 and an average age of 60.3 years. 82.3% of patients had an ECOG score of 0-1 and 17.8% frail patients had an ECOG score of 2-3. IgG type was more common (51.1%). Patients are prone to developing anemia (51.1%), elevated globulin (52.1%), high urinary protein (55.6%), renal dysfunction (28.9%), extramedullary tumors (17.8%). ISS-III staging accounted for 53.3%, while R-ISS staging and R2-ISS staging are mainly at moderate risk. 81.4% patients had high-risk cytogenetics, including 17p deletion (20.9%), 1q21 gain/amplification (65.1%), 1p32 deletion (23.8%), t(4,14) (20.9%), double hit 30.2%. Some patients have experienced elevated BNP levels (19.1%), decreased cardiac systolic function (18.9%) and hypertension (28.9%) before treatment. 51% patients had received autologous hematopoietic stem cell transplantation treatment. 30 patients were in first relapse, and 15 cases have received second-line treatment or above. 100% patients had bortezomib exposed, 95.5% patients had lenalidomide exposed, of which 35 were resistant (81.4%), double resistant (64.4%).
The median duration of DKD treatment was 6 (1-13), with an ORR of 88.3% and a CR rate of 46.5%. The negative rate of NGF-MRD with 10-5 level was 31.1%. Among them, the ORR of patients with first relapse was 90%, with a CR rate of 46.6%. The ORR of patients with multiple relapses was 84.6%, with a CR rate of 46.1%. Among them, 11 cases terminated treatment due to disease progression, 2 cases died from the disease, and 1 case requested a change in treatment plan due to economic reasons.
The median follow-up time was 9 (1-19) months, the estimated median PFS was 15 months, and the median OS was not reached. The cumulative PFS of the first relapse subgroup at 12 months was 71.6%, while that of the multiple relapse subgroup was 76.0%, there was no significant difference between the two groups. The prognosis of patients with extramedullary tumors was significantly worse, with a median PFS of only 8 months (P=0.0173). According to mSMART3.0 staging, the 12-month cumulative PFS for standard risk, high risk (one hit), and high risk (double hit) were 100%, 80.4%, and 50.4% respectively (P=0.0735).
40% patients received a sufficient dose of 56mg/m2*2d-70mg/m2/d a week for treatment. The main reason for the reduction was due to AEs during treatment, especially hematological toxicities (31/45, 68.9%), with thrombocytopenia being the most common (20/45, 44.4%), and the vast majority being grade III-IV reactions (33.3%,15/45), the following one was neutropenia (20%, 9/45). Among the non-hematological AEs (17/45, 37.8%), there were 22.2% respiratory infection, mainly grade I-II (80%, 8/10), 4 cases of hypertension events, and stable blood pressure control after antihypertensive treatment.
Conclusion:
DKD showed high response rate, high CR rate in this real-world multi-center studies of patients with RRMM. But the prognosis of patients with double-hit abnormalities and extramedullary tumors was significantly worse. Hematological AEs were more likely to occur, requiring adjustment of drug dosage.