(C-214) Second Primary Malignancy in Patients with Multiple Myeloma Receiving Chimeric Antigen Receptor T-Cell Therapy and Other Systemic Anticancer Therapy: A Comparative Study Using a Real-World Database

Background: Cases of second primary malignancy (SPM) have been reported following chimeric antigen receptor T-cell (CAR T) therapy, but comparative studies are scarce.

Objectives: To compare the risk of SPM following CAR T therapy vs other systemic anticancer therapy (SACT) in patients with multiple myeloma (MM).

Methods: Patients aged ≥18 years with MM who initiated CAR T therapy or other SACT in second-line or beyond were identified from Komodo Health claims data (3/26/2021–1/31/2024). Incident SPM was identified by ≥1 diagnostic code from index treatment to death, disenrollment, or data cutoff (4/30/2024), whichever was earliest. Inverse probability of treatment weighting was applied to balance baseline risk factors including prior MM treatments. Cumulative incidence of any, solid, and heme SPM following CAR T therapy or other SACT was estimated through 24 months; p-values were calculated for differences in the area under the curves through 24 months.

Results: The study followed 435 patients who received CAR T therapy and 12,268 patients who received other SACT for a median of 11.8 months (IQR 5.7–22.8). Compared to pts who received other SACT, pts who received CAR T therapy had similar risk (cumulative incidence [95% CI]) of any SPM (p = 0.31; 24.1% [18.2%, 31.9%] vs. 22.3% [19.2%, 25.8%] at 24 months) and solid SPM (p = 0.31, 9.1% [5.7%, 13.1%] vs. 11.5% [9.2%, 14.5%] at 24 months), but significantly higher risk of heme SPM (p=0.04; 8.7% [5.7%, 12.0%] vs. 6.3% [4.9%, 8.4%] at 6 months, 12.1% [8.5%, 16.0%] vs. 8.9% [7.0%, 11.1%] at 12 months, and 17.9% [12.8%, 24.5%] vs. 13.1% [10.6%, 16.4%] at 24 months; respectively), mainly driven by higher risks of myelodysplastic syndrome and leukemias. In the sensitivity analysis requiring ≥2 diagnostic codes to identify an SPM, the absolute risk was reduced and the difference in heme SPM risk was attenuated (p=0.09; CAR T therapy: 5.5% [3.1%, 8.0%] vs other SACT: 4.9% [3.4%, 7.0%]). Notably, patients were more likely to receive bone marrow examination following CAR T therapy vs other SACT, particularly early in the follow-up (47% vs 13% at 0–3 months, respectively).

Conclusions: Patients with MM appeared to have a higher risk of heme SPM through 24 months following CAR T therapy compared with other SACT. However, the difference was attenuated in a sensitivity analysis that required ≥2 diagnostic codes, assumed to represent a confirmed diagnosis. Potential detection bias may exist, suggested by a higher rate of bone marrow examination following CAR T therapy. Longer term studies are needed to further evaluate this association.