https://orcid.org/0000-0002-8216-3457
Key Points
In patients with de novo DLBCL and transformed FL, 2L vs 3L CART performs similarly in unselected patients and primary refractory disease.
In patients with double or triple-hit lymphoma, 2L CART offers a survival benefit over later lines and should be prioritized.
CART has transformed the management of relapsed and refractory large B-cell lymphoma, but real-world outcomes data is needed to confirm the benefits seen in clinical trial settings. We performed a multicenter retrospective analysis evaluating CART outcomes according to line of therapy, specifically 2L vs 3L vs 4L and beyond (4L+). We included patients who underwent CD19-directed CART for de novo DLBCL or transformed follicular lymphoma. Overall (n=466), 21% (n=98) of patients received CART as 2L, 41% (n=192) as 3L, and 38% (n=176) as 4L+. Median follow-up from CART infusion was 35 months in surviving patients. ORR and CR were similar for 2L vs 3L vs 4L+. From CART infusion, mPFS and mOS were similar for 2L vs 3L, but shorter in 4L+ patients (mPFS 11.6 vs 12.7 vs 5.7 months, p<0.001; mOS NR vs 69.4 vs 21.9 months, p<0.001). In patients with double-hit or triple-hit lymphoma (DHL/THL), receiving CART in 2L versus 3L significantly improved three-year overall survival (63% [2L] vs 32% [3L], p=0.01). Patients with disease that required bridging therapy were also at increased risk of progression or death. In patients who received subsequent therapy after CART failure, line of therapy did not impact mPFS or mOS. Overall, our findings inform real-world practice wherein CART as 2L versus 3L yields similar survival outcomes in unselected patients. However, patients specifically with DHL/THL should be considered for CART in the 2L outside of the PRD or early relapsed setting.
