P-263: Treatment patterns and clinical outcomes in multiple myeloma patients previously treated with lenalidomide and an anti-CD38 monoclonal antibody: findings from the PREAMBLE registry

Introduction: Lenalidomide (LEN) and anti-CD38 monoclonal antibody (mAb)-based regimens are increasingly being incorporated early in the treatment of multiple myeloma (MM). With the evolving MM treatment landscape, understanding real-world treatment patterns and clinical outcomes in patients previously treated with LEN and an anti-CD38 mAb can help in assessing unmet needs.

Methods: PREAMBLE is a prospective, observational registry that enrolled MM patients in the US, Canada and Europe between 2012 and 2020. Patients eligible for this study were previously treated with LEN and an anti-CD38 mAb in the same or different lines of therapy (LOTs) and initiated a subsequent LOT (index date=date of subsequent LOT initiation). Demographics, clinical characteristics, treatment history, and index treatment regimens were summarized descriptively. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method in the overall population and across subgroups defined by region (United States [US] vs ex-US), index LOT (2-4L vs 5L+), age ( < 75 vs ≥75 years), and refractory status [refractory to both LEN and an anti-CD38 mAb vs not, triple-class refractory (TCR) vs not].

Results: Of 215 eligible patients, most were male (55.8%) and from the US (52.1%), and the median age was 69 years (range 45–92 years). Median time from MM diagnosis to index date was 3.8 years (range 0.3–29.3 years). Median number of prior treatment lines was 3 (range 1–12). Over half (50.7%) of all patients had undergone stem cell transplantation prior to the index date. All patients had previously received daratumumab; 95.8% of patients were also exposed to a proteasome inhibitor, the majority of whom had received bortezomib (95.1%). 80.9% of patients were refractory to LEN and an anti-CD38 mAb and more than half (69.3%) were TCR. Patients’ index regimens included approximately 70 different treatment combinations, with carfilzomib ± dexamethasone (Kd; 13.0%), daratumumab/pomalidomide ± dexamethasone (DPd; 7.9%), and pomalidomide ± dexamethasone (Pd; 6.5%) being the most common. The median PFS in the cohort was 5.2 months (95% confidence interval [CI] 3.7–6.7 months) and the median OS was 16.2 months (95% CI 10.3–not reached [NR] months). Some subgroups had numerically worse survival outcomes (ex-US, later LOTs, ≥75 years, refractory to both LEN and an anti-CD38 mAb, and TCR), but only patients who were TCR had significantly shorter OS than those who were not (16.0 months, 95% CI 12.3–21.2 months vs 31.2 months, 95% CI 25.6–NR months).

Conclusions: Data from this analysis show that after exposure to LEN and an anti-CD38 mAb, MM patients have poor survival outcomes and no clear standard of care. This analysis highlights the need for more effective treatment options for this patient population.