Long-Duration Complete Remissions of Diffuse Large B Cell Lymphoma after Anti-CD19 Chimeric Antigen Receptor T Cell Therapy.

T cells expressing anti-CD19 chimeric antigen receptors (CARs) can induce complete remissions (CRs) of diffuse large B cell lymphoma (DLBCL). The long-term durability of these remissions is unknown. We administered anti-CD19 CAR T cells preceded by cyclophosphamide and fludarabine conditioning chemotherapy to patients with relapsed DLBCL. Five of the seven evaluable patients obtained CRs. Four of the five CRs had long-term durability with durations of remission of 56, 51, 44, and 38 months; to date, none of these four cases of lymphomas have relapsed. Importantly, CRs continued after recovery of non-malignant polyclonal B cells in three of four patients with long-term complete remissions. In these three patients, recovery of CD19+ polyclonal B cells took place 28, 38, and 28 months prior to the last follow-up, and each of these three patients remained in CR at the last follow-up. Non-malignant CD19+ B cell recovery with continuing CRs demonstrated that remissions of DLBCL can continue after the disappearance of functionally effective anti-CD19 CAR T cell populations. Patients had a low incidence of severe infections despite long periods of B cell depletion and hypogammaglobulinemia. Only one hospitalization for an infection occurred among the four patients with long-term CRs. Anti-CD19 CAR T cells caused long-term remissions of chemotherapy-refractory DLBCL without substantial chronic toxicities.

Kochenderfer JN ，Somerville RPT ，Lu T ，Yang JC ，Sherry RM ，Feldman SA ，McIntyre L ，Bot A ，Rossi J ，Lam N ，Rosenberg SA ... -  《-》

Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T cells expressing an anti-CD19 chimeric antigen receptor.

Kochenderfer JN ，Dudley ME ，Kassim SH ，Somerville RP ，Carpenter RO ，Stetler-Stevenson M ，Yang JC ，Phan GQ ，Hughes MS ，Sherry RM ，Raffeld M ，Feldman S ，Lu L ，Li YF ，Ngo LT ，Goy A ，Feldman T ，Spaner DE ，Wang ML ，Chen CC ，Kranick SM ，Nath A ，Nathan DA ，Morton KE ，Toomey MA ，Rosenberg SA ... -  《-》

Phase II trial of co-administration of CD19- and CD20-targeted chimeric antigen receptor T cells for relapsed and refractory diffuse large B cell lymphoma.

Anti-CD19 chimeric antigen receptor T (CAR-T) cell therapy has demonstrated remarkable efficacy for refractory and relapsed diffuse large B cell lymphoma (R/R DLBCL). However, this therapy failed in nearly 25% patients mainly due to antigen loss. The authors performed a phase Ⅱ trial by coadministration of anti-CD19 and anti-CD20 CAR-T cells treatment for R/R DLBCL and evaluated its efficacy and toxicity. Totally 21 patients with DLBCL were enrolled in this study. The patients were conditioned with fludarabine and cyclophosphamide before the infusion of anti-CD19 and anti-CD20 CAR-T cells. Treatment response, toxicity, and persistence were monitored continuously. Of the 21 patients received the treatment, the objective response rate (ORR) is 81.0% (95% confidence interval [CI], 58.1%-94.6%) with four cases of bulk (4/5) and one case of testis involvement; 52.4% (95% CI, 29.8%-74.3%) had a complete response (CR). Peak levels of anti-CD19 and anti-CD20 CAR cells were associated with response (P = .007 and .002). Grade 3-4 cytokine release syndrome (CRS) and neurologic events occurred in 28.5% and 9.5% patients, respectively. Median overall survival (OS) and progression-free survival (PFS) were 8.1 and 5.0 months, respectively. The maximum standard uptake value (SUVmax) of CD4/CD8 ratio before and after infusion were associated with responses, and the total lesion glycolysis (TLG) before infusion correlates with cytokines level. Coadministration of anti-CD19 and CD20 CAR-T cells therapy for DLBCL is feasible with manageable toxicity. Cytokine markers are related to toxicity and SUVmax could predict efficacy. This trial was registered at www.clinicaltrials.gov as NCT03207178.

Sang W ，Shi M ，Yang J ，Cao J ，Xu L ，Yan D ，Yao M ，Liu H ，Li W ，Zhang B ，Sun K ，Song X ，Sun C ，Jiao J ，Qin Y ，Sang T ，Ma Y ，Wu M ，Gao X ，Cheng H ，Yan Z ，Li D ，Sun H ，Zhu F ，Wang Y ，Zeng L ，Li Z ，Zheng J ，Xu K ... -  《Cancer Medicine》

Lymphoma Remissions Caused by Anti-CD19 Chimeric Antigen Receptor T Cells Are Associated With High Serum Interleukin-15 Levels.

Kochenderfer JN ，Somerville RPT ，Lu T ，Shi V ，Bot A ，Rossi J ，Xue A ，Goff SL ，Yang JC ，Sherry RM ，Klebanoff CA ，Kammula US ，Sherman M ，Perez A ，Yuan CM ，Feldman T ，Friedberg JW ，Roschewski MJ ，Feldman SA ，McIntyre L ，Toomey MA ，Rosenberg SA ... -  《-》

Long-Term Follow-Up of Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy.

Cappell KM ，Sherry RM ，Yang JC ，Goff SL ，Vanasse DA ，McIntyre L ，Rosenberg SA ，Kochenderfer JN ... -  《-》