Recovery of humoral immunity in patients with durable complete responses following chimeric antigen receptor modified t cells directed against CD19 (CTL019).

7564 Background: Autologous T cells genetically modified to express a chimeric antigen receptor with an external anti-CD19 antibody domain, and CD3ζ and 4-1BB signaling domains (CTL019) can achieve remissions in patients (pts) with relapsed/refractory (r/r) CD19+ non-Hodgkin lymphomas (NHL). We studied the effect of this therapy on humoral immunity. Methods: Serial immunoglobulin (Ig) levels were measured in pts with complete response (CR) to CTL019 on a phase II trial. Pts had r/r CD19+ follicular lymphoma (FL), diffuse large B cell lymphoma (DLBCL), or mantle cell lymphoma (MCL). After collection of lymphocytes, pts received lymphodepleting chemotherapy followed 1 - 4 days later by 1 - 5 x 108CTL019 cells intravenously. Response was assessed every 3 months (mo) for 24 mo. Enrollment is reported from Feb 2014 – Nov 2015, survival analyses through Jan 2016. Results: 43 pts enrolled: median age 56 years (range 25-77); female: male ratio 17:26; median prior therapies 4 (range 1-19); prior ASCT 14 (33%). 30 pts received CTL019; 29 are evaluable for response (15 DLBCL; 13 FL; 1 MCL). Best overall response rate is 59% (17/29); CR 52% (15/29); DLBCL CR 40% (6/15); FL CR 69% (9/13). To date, no pt in CR has relapsed (median follow up 14 mo). 2 pts were receiving IV Ig before CTL019; 2 pts started IV Ig after CTL019 for hypogammaglobulinemia with frequent infections. 10 pts (6 DLBCL; 4 FL) in CR > 5 mo (median 17 mo; range 5-21) did not received IV Ig and had no > grade 2 or recurrent infections. Baseline IgG levels were decreased in all 10 pts (median 514 mg/dL; range 200-639; normal > 650), IgA in 6/10 pts (median 46 mg/dL; range 34-134; normal > 50), and IgM in 8/10 pts (median 28 mg/dL; range 8-74; normal > 40). 4/10 pts had IgG recovery to their baseline level (1 pt at 21 mo) or to normal levels at 6, 9, and 15 mo (total % IgG increases: 10%, 19%, 29%, respectively). 2/10 pts had IgA recovery to > baseline levels (total % IgA increases 3% and 17% at 18 mo). 5/10 pts had total % IgM increases: 6% at 18 mo, 13% at 12 mo, 21% at 12 mo, 46% at 9 mo, and 441% at 15 mo. Conclusions: In adult r/r NHL pts, CTL019 cells can induce a sustained CR during which Ig levels may improve. Most pts do not need Ig replacement after CTL019 therapy. Clinical trial information: NCT02030834.