(PA-447) Outcomes of Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplant Following VRD or KRD Induction Therapy

The optimal induction regimen for patients with newly diagnosed multiple myeloma (NDMM) remains an area of ongoing investigation. Real-world comparative data on outcomes following bortezomib, lenalidomide, and dexamethasone (VRD) versus carfilzomib, lenalidomide, and dexamethasone (KRD) induction prior to autologous hematopoietic cell transplantation (autoHCT) is limited.

Methods:

We conducted a single-center retrospective analysis of patients with NDMM who received VRD or KRD induction followed by upfront autoHCT between 2006 -2021. All cytogenetic risk groups were included. High-risk cytogenetic abnormalities (HRCA) were defined as del(17p), t (4;14), t (14;16) or 1q21 gain or amplification (1q+) by FISH.

Results:

1129 patients were included in the analysis, 364 received KRD induction and 765 received VRD. The median age was 61.9 years (range 25.4 – 82.6). Baseline characteristics were mostly balanced between the two groups, though the KRD group had a higher proportion of patients with HRCA (43% vs. 32%; p< 0.001), Second Revision of the International Staging System (R2-ISS) stage III/IV disease (38%/9% vs. 34%/5%; p=0.008), creatinine ≤2 mg/dL (95% vs. 90%; p=0.007) and more often received busulfan-melphalan conditioning (22% vs. 15%; p=0.005). 

KRD was associated with higher response rates compared to VRD across all timepoints: ≥CR and ≥VGPR] pre-transplant 23% and 71% vs. 16% (p=0.006) and 61% (p < 0.001); at day 100 post-transplant: 47% and 85% vs. 38% (p=0.003) and 80% (p=0.050); at best post-transplant response:71% and 93% vs. 60% (p < 0.001) and 89% (p=0.07), respectively. A higher proportion of patients treated with KRD achieved MRD negativity prior to transplant (49% vs. 42%, p=0.027).  

With a median follow-up of 38.6 months (range 0.3 – 172.8), median PFS was significantly longer in the KRD group compared to VRD (62.2 months vs. 48.7 months; p=0.009). 5-year PFS rate was 52% with KRD compared to 44% with VRD. Median OS was not reached with KRD vs. 122.7 months with VRD (HR 1.16, 95% CI 0.80–1.68, p=0.43). 

KRD induction was associated with improved PFS in a weighted multivariable analysis (hazard ratio [95% CI] 0.76 [0.60–0.97], p=0.026). Subgroup analysis showed PFS benefit for KRD in patients with standard-risk cytogenetics (0.51 [0.35-0.74]), patients aged < 65 years (0.74 [0.55-0.99]) and male patients (0.61 [0.44-0.84]), whereas there was no significant advantage for KRD in patients with HRCA (0.82 [0.60-1.12]), patients aged ≥65 years (0.75 [0.52-1.07]) and female patients (0.91 [0.66-1.26]). 

Conclusions:

In a large real-world study, KRD induction was associated with higher response rates and longer PFS compared to VRD in NDMM patients who received upfront autoHCT. Subgroup analysis showed significant PFS advantage for KRD in patients with standard-risk cytogenetics, those aged < 65 years and male patients.