Factors impacting treatment choice with a CD38 antibody, immunomodulator, proteasome inhibitor, and dexamethasone in first line multiple myeloma patients: A real-world US study

Abstract Background In 2023, the NCCN first listed a quadruplet (quad) regimen of a CD38 Antibody, Immunomodulator, Proteasome Inhibitor, and Dexamethasone for newly diagnosed multiple myeloma (NDMM) patients (pts), based on the GRIFFIN study. The FDA approved daratumumab, lenalidomide (R), bortezomib (V), and dexamethasone (d) (dara-RVd) for transplant-eligible pts in July 2024, and isatuximab-RVd for transplant-ineligible pts in September 2024. The phase 3 PERSEUS trial further confirmed the superiority of D-RVd over RVd. This real-world (RW) study aimed to identify factors influencing quad induction therapy in first-line therapy (LOT-1) NDMM pts. Methods This retrospective analysis used data from the IntegraConnect PrecisionQ RW de-identified database, consisting of >3 million cancer pts across >500 care sites in the United States. The study included MM pts, age ≥18, initiating LOT 1 therapy between January 1, 2024, and March 31, 2025. LOT 1 is further defined as drugs given within 60 days of the initial induction start date. Pts with a second primary cancer were excluded unless chart curation confirmed the diagnosis of MM as the primary malignancy. Pts considered quad eligible were age ≤80 and Eastern Cooperative Group performance status (ECOG PFS) ≤2. Pts without an ECOG score at LOT 1 start were excluded. Quad therapy was operationally defined as receipt of all four drug classes within the first 60 days, irrespective of sequencing or care setting. Quad eligible pts were assessed to evaluate whether age, gender, race, ECOG PFS, renal function as defined by estimated glomerular filtration rate (eGFR) (<30,30-60,>60), or high risk NDMM cytogenetics including deletion 17p, t4;14 or 1q (CG-risk) impacted treatment selection, with none vs. 1 vs. ≥2 high risk abnormalities used to stratify cytogenetic risk accordingly. Only pts who were manually abstracted were included in the analysis for cytogenetics. Only pts with eGFR results within 30 days of first line were evaluated for whether eGFR results impacted treatment. Data are presented using descriptive statistics and comparisons were performed using chi-squared analysis (p<0.05 vs NS). Results Of 1,721 quad-eligible pts with NDMM who initiated LOT 1 therapy, 54.2% were male, 52.9% were White, and the median age was 69 (IQ range 61–74 years). Overall, 47.1% received a quad, with 38.1% (n = 357) in Q1 2024 and 53.4% (n = 334) in Q1 2025. Quad use was higher in pts ≤65 years of age at 55.1% (n = 650) than those >65 years of age at 42.2% (n = 1071) (p<0.01). Gender had no significant impact on quad use, with rates of 46.5% for females (n = 787) and 47.6% for males (n = 933). Race had no significant impact on quad use, with rates of 49.1% for White (n = 911), 42.4% for Black/African American (n = 238), and 46.2% for Other (n = 572). For ECOG PFS, 48.8% of ECOG 0 (n = 875), 46.9% of ECOG 1 (n= 659), and 39.6% of ECOG 2 (n = 187) pts received a quad (NS). Quad use was as follows by eGFR (n = 242): 46.8% in eGFR >60 pts (n =173), 36.0% in eGFR 30-60 pts (n = 50), and 26.3% in eGFR <30 pts (n = 19) (NS). Quad use was as follows by NDMM CG-risk (n = 64): 21.1% in negative pts (n = 19), 63% in ≤1 positive pts (n = 38), and 71% in ≥2 positive pts (n = 7) (p<0.01). Conclusion Despite NCCN recommendations and FDA approvals, this RW study shows an important treatment gap as only 53% of eligible pts received a quad regimen by Q1 2025 across >500 care sites. Age and NDMM CG-risk were found to be statistically significant factors in treatment selection. Race, ECOG PFS and renal function showed differences in quad use, but were not statistically significant. Further research is warranted to pinpoint logistical obstacles to quad uptake, and planned follow-up analyses in this cohort will compare real-world progression-free survival as well as healthcare-resource utilization between quadruplet and triplet induction to quantify the added clinical value of early use of quadruplet therapy in NDMM. These data also suggest increasing educational awareness of emerging evidence and evolving standards of care are essential to ensure clinical practice keeps pace with therapeutic advances.

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