Details

Autor(en) / Beteiligte

• Awasthi, R.
• Waldron, E.
• Grupp, S.A.
• Pulsipher, M.A.
• Bader, P.
• Schuster, S.J.
• Maziarz, R.
• Waller, E.
• Jager, U.
• Thieblemont, C.
• Dreyling, M.
• Fowler, N.
• Maier, H.J.
• Willert, J.

Titel

LONG-TERM DURABLE RESPONSES IN PATIENTS (PTS) WITH RELAPSED/REFRACTORY (R/R) ACUTE LYMPHOBLASTIC LEUKEMIA (ALL), DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL), AND FOLLICULAR LYMPHOMA (FL) TREATED WITH TISAGENLECLEUCEL (TISA-CEL) AND ITS ASSOCIATION WITH PERSISTENCE OF CHIMERIC ANTIGEN RECEPTOR (CAR) T CELLS

Ist Teil von

• Cytotherapy (Oxford, England), 2024-06, Vol.26 (6), p.S152-S152

Ort / Verlag

Elsevier Inc

Erscheinungsjahr

2024

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• onitoring CAR transgene level in peripheral blood post tisa-cel infusion provides data on CAR-T cell expansion and persistence. We analyzed the impact of CAR persistence and B-cell aplasia on DOR in pts treated with tisa-cel. Transgene levels measured by qPCR were available from trials in r/r ALL (ELIANA, ENSIGN, NCT03123939, NCT01626495), DLBCL (JULIET), FL (ELARA), and long-term follow-up study (NCT02445222). Impact of duration of Tloss (time when transgene levels first dropped to <50 copies/µg DNA [LLOQ] after maximal expansion) and ongoing persistence beyond 1 year along with time to B-cell recovery (ALL: >1% CD19+ B-cells/WBC or >3% CD19+ B-cells/lymphocytes) on DOR/relapse were investigated Long-term CAR persistence in tisa-cel-treated pts was observed for up to 9, 6, and 2.5 years for ALL, DLBCL, and FL, respectively, reflecting differing length of follow-up due to initiation of trials. In ALL, pts who lost transgene in ≤6 or 6-12 months (mo) had shorter DOR vs pts with persistent transgene (Fig). In ALL, median Tloss was 27.4, 18.2, 9.7, and 18 mo for ongoing CR >12 mo, CR pts between 6-12 mo, relapsed pts <12 mo, and relapsed pts >12 mo, respectively. In pts who lost transgene ≤6 mo, durable responses for ≥12 mo were maintained in some pts — ALL: 29%; DLBCL: 15%; FL: 50%. Among ALL-relapsed pts, 17/26 (65%) with Tloss at <6 mo showed B-cell recovery; 6 pts had Tloss at <6 mo and B-cell recovery but maintained response for ≥12 mo. In ALL, NGS MRD ≤6 mo to 1 year post infusion may be a more reliable predictor of potential relapse than B-cell recovery (Pulsipher MA et al., 2022). Median time to B-cell recovery was 266 days in relapsed/censored pts ≤12 mo but was not reached for pts with ongoing response at 12 mo. Of ALL pts with CAR persistence, longer DOR observed in pts (with <50% blasts) prior to tisa-cel infusion vs pts with ≥50% blasts reflect more resistant high-risk ALL at study entry or greater potential for stochastic loss of CD19 in higher disease burden pts. Long-term sustained remission was observed in tisa-cel–treated pts in pivotal trials. A positive association between CAR persistence and durable responses across indications was demonstrated; however, some pts maintained durable responses despite early loss of transgene and/or early B-cell recovery. In DLBCL and FL, the transgene levels in blood may not represent levels at target sites including lymph nodes. Also, persistence or Tloss are dependent on the duration of follow-up and LLOQ