P-279: Efficacy and Safety of Carfilzomib, Lenalidomide, and Dexamethasone Versus Ixazomib, Lenalidomide, and Dexamethasone in Real world Patients with Relapsed/Refractory Multiple Myeloma: KMM2004 study

Introduction: The recent influx of novel agents with different mechanisms of action has led to rapid changes in treatment strategies and outcomes of multiple myeloma. However, in South Korea, where national health insurance service strongly influences drug selection, the lenalidomide based triplet remains the most effective treatment option for RRMM. The approval of KRd in 2018, followed by IRd in 2020, has raised questions about the most effective treatment strategies for patients with RRMM.

Methods: We retrospectively reviewed the medical records of 182 RRMM patients treated with KRd (112) or IRd (70) at 17 centers in South Korea from May 2020 to April 2021. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), overall response rate (ORR), and safety.

Results: Median age (65 vs 66 yrs ; p=0.38) and R-ISS at diagnosis (I: 13.3 vs 21.7%, II: 54.3 vs 48.3% and III: 32.4 vs 30.0%, p=0.38) were not significantly different between the two groups. The trial feasibility to participate in the clinical trial was similar in both groups (83.0 vs 87.1%, p=0.46). Prior treatment history and response to prior therapy were also similar in both groups. Approximately 92% of patients were treated as a second line and the number of patients who had received ASCT was the same at 49% in both groups. Patients with high risk cytogenetics were more likely to be treated with KRd (43.8 vs 18.0%, p=0.003) and the time from diagnosis to XRd treatment was longer in the IRd gorup (20.5 vs 33.7 mo, p=0.08).
Patients in the KRd group received 13 cycles of treatment and patients in the IRd group received 15 cycles of treatment (median, p=0.1), with more dose modifications in the IRd group (30.1 vs 41.1%, p=0.023). ORR was not significantly different at 89.1 vs 87.0% (p=0.67), but CRR was better in the KRd group (45.5 vs 30.4%, p=0.046). Median PFS (19.1 vs 28.4 mo, p=0.08) showed a trend towards better outcomes in the IRd group, although not statistically significant, and median OS (31.6 vs not reached, p=0.02) was statistically significantly better in the IRd group. In subgroup analysis, patients with older than 65 years (HR 0.41, p=0.006), normal renal function (HR 0.52, p=0.045), ISS I or II (HR 0.5, p=0.03), extramedullary plasmacytoma (HR 0.35, p=0.02), and PR acheieved (HR 0.59, p=0.04) showed better PFS outcomes with IRd.
In the safety analysis, hematologic toxicity, infection, and cardiac events were more frequent in the KRd group, and GI toxicity and skin rash were relatively more frequent in the IRd group.

Conclusions: Our data showed the treatment outcomes of KRd and IRd in the real-world. Contrary to predictions based on clinical trials, the IRd group showed better survival data. Clinicians tended to choose KRd in the high risk group and it actually showed a deeper response. In contrast, the IRd group did not acheieve a deeper response, but the treatment response was found to be sustainted for a longer period of time.