(PA-456) Treatment Outcomes in Isolated Gain1q Multiple Myeloma Patients

Risk-adaptive treatment for newly diagnosed multiple myeloma (MM) is crucial for optimizing outcomes. High-risk disease is heterogenous across a variety of cytogenetic abnormalities (CA), of which extra copies of 1q is the most prevent. While the presence of >3 copies (amp1q) has worse outcomes than 3 copies (gain1q), gain1q is itself an independent high-risk factor incorporated into R2-ISS. Gain1q can occur in combination with other high-risk CA or in isolation, but the majority of phase III RCTs do not specify these nuances, impeding understanding of therapy-related outcomes for this subgroup. To better tailor therapies in patients with isolated gain1q, evaluating different components to frontline treatment is paramount. We performed a retrospective analysis of treatment characteristics and outcomes for patients with an isolated gain1q and amp1q. This is the first study in isolated gain1q that includes daratumumab (dara)-based regimens and will provide insights into managing such patients.

Methods:

This is a single-center, retrospective cohort study at the Yale Cancer Center from January 1, 2017 to November 1, 2024. Patients (pts) with a new diagnosis of MM and copy number change in chromosome arm 1q were included. Patients were excluded if they had other high-risk CA. The primary endpoint was progression free and overall survival within the gain1q cohort stratified by induction regimen, use of autologous stem cell transplant (ASCT), and doublet verses single agent in maintenance. The secondary endpoints are PFS and OS comparison between gain1q and amp1q cohorts.

Results:

A total of 72 pts were identified with isolated gain1q and 16 pts with isolated amp1q. Median follow-up was 3.42 years for gain1q and 3.52 years for amp1q cohorts. Within the gain1q cohort, 24% received dara as quadruple and 11% as triplet therapy, 38% received VRd, 18% KRd, and 10% CyBorD. Of the entire cohort, 43% of pts received an ASCT and 40% had doublet maintenance. Within the dara-treated cohort, 52% of pts received an ASCT and 100% continued maintenance therapy with two agents, of which 72% were dara and lenalidomide. The use of dara-based induction regimens significantly prolonged PFS with a 5-year PFS of 85% compared to 44% for all others (p=0.044). In addition, the use of ASCT resulted in a 5-year OS of 100% compared to 64% without (p=0.0022). Secondary endpoints demonstrated that amp1q was associated with shortened PFS (p=0.04) and OS (p=0.015) compared to gain1q.

Conclusions:

Our study demonstrates treatment characteristics associated with improved outcomes in isolated gain1q. The use of dara-based therapy is shown to improve PFS within this specific cohort, which is aligned with subgroup analyses from both isatuximab-based phase III trials and dara-based phase II GRIFFIN trial. We also demonstrate an OS benefit with ASCT. Further analysis is needed to evaluate long-term outcomes of dara with and without transplant, and duration of dara in maintenance.