Retreatment (reTx) of patients (pts) with refractory large B-cell lymphoma with axicabtagene ciloleucel (axi-cel) in ZUMA-1.

Authors

Frederick Locke

Frederick Lundry Locke

H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL

Frederick Lundry Locke , Nancy L. Bartlett , Caron A. Jacobson , Olalekan O. Oluwole , Javier Munoz , Lazaros J. Lekakis , Max S. Topp , Irit Avivi , Jenny J. Kim , Rong Chu , Lianqing Zheng , John M. Rossi , Adrian Bot , Sattva Swarup Neelapu

Organizations

H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, Washington University School of Medicine and Siteman Cancer Center, St Louis, MO, Dana-Farber Cancer Institute, Boston, MA, Vanderbilt University Medical Center, Nashville, TN, Banner MD Anderson Cancer Center, Gilbert, AZ, University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL, Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany, Sourasky Medical Center, Tel Aviv, Israel, Kite, a Gilead Company, Santa Monica, CA, The University of Texas MD Anderson Cancer Center, Houston, TX

Research Funding

Pharmaceutical/Biotech Company
Kite, a Gilead Company

Background: Axi-cel, an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy, is approved in the US and EU for pts with relapsed/refractory large B cell lymphoma after ≥ 2 prior therapies. In the ZUMA-1 pivotal study (NCT02348216), the objective response rate (ORR) was 83% (58% complete response [CR] rate; Locke et al. Lancet Oncol. 2019). While axi-cel has demonstrated durable responses in a subset of pts, approximately half of all responders relapsed, and little is known on the viability of reTx with CAR T cell therapy. Here we report outcomes of pts retreated with axi-cel in ZUMA-1. Methods: Pts with progressive disease (PD) were eligible for reTx if there was no evidence of CD19 loss by local review, and if during 1st Tx they did not experience any dose-limiting toxicities, as defined in Phase 1, or comparable toxicities in Phase 2. Pts received the same regimen at reTx as at 1st Tx: 2 × 106 CAR T cells/kg after conditioning chemotherapy. Results: Thirteen pts in Cohorts 1 – 4 received axi-cel reTx. Prior to 1st Tx, most pts (69%) had an IPI score 3-4, 85% had disease stage 3-4, and the median number of prior regimens was 3 (range, 2 – 6). At first Tx, 6 pts achieved a CR, 6 achieved partial response (PR), and 1 pt had stable disease (SD) prior to PD. Median duration of first response was 96 days (range, 56 – 274). There was no Grade ≥ 3 cytokine release syndrome (CRS; 6 pts each had Grade 1 and 2). There were no Grade 4 or 5 neurologic events (NEs; 2 pts had Grade 1, 1 had Grade 2, and 7 had Grade 3). Upon reTx, 54% of pts achieved response (4 CR, 3 PR). Response to reTx was more common among pts who achieved CR at 1st Tx (83%; 4/6 CR, 1 PR, 1 SD) than in pts who achieved PR at 1st Tx (33%; 2/6 PR, 1 SD, 3 PD), and no response was observed in the pt with SD at 1st Tx. Median duration of response at reTx was 81 days (range, 1 – 225+). Response with reTx was longer than that with 1st Tx for 2 pts. One pt remains in response 255 days post-reTx. Comparable rates of CRS were observed with reTx as with 1st Tx. Compared with 1st Tx, fewer pts experienced NEs with reTx, and those that did occur were of lower grade: 23% (3 of 13 pts) had Grade 3; 23% (3 of 13 pts) had Grade 1, and 8% (1 of 13 pts) had Grade 2. Peak CAR T cell expansion was lower upon reTx vs 1st Tx (median, 4.3 vs 66.1 CAR gene-marked cells/µL blood). Conclusions: Based on this limited sample size, reTx with axi-cel may have clinical efficacy, although transient, in some pts, especially those who achieve CR with 1st Tx. CAR T cell expansion and severe CRS and NEs may be attenuated at reTx. Further studies with additional pts are needed to confirm these results. Clinical trial information: NCT02348216.

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Abstract Details

Meeting

2020 ASCO Virtual Scientific Program

Session Type

Poster Discussion Session

Session Title

Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia

Track

Hematologic Malignancies

Sub Track

Non-Hodgkin Lymphoma

Clinical Trial Registration Number

NCT02348216

Citation

J Clin Oncol 38: 2020 (suppl; abstr 8012)

DOI

10.1200/JCO.2020.38.15_suppl.8012

Abstract #

8012

Poster Bd #

345

Abstract Disclosures