Autologous hematopoietic stem cell transplantation in tandem with anti-CD30 CAR T-cell infusion in relapsed/refractory CD30+ lymphoma.

Authors

null

Xiuxiu Yang

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

Xiuxiu Yang , Peiling Zhang , Yang Cao , Jue Wang , Mi Zhou , Chunrui Li , Jianfeng Zhou , Liang Huang

Organizations

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China

Research Funding

Other

Background: Long-term outcome is unfavorable for patients with relapsed/refractory (r/r) classical Hodgkin lymphoma (cHL) who are resistant to salvage chemotherapy, even followed by autologous stem cell transplantation (ASCT). Long-term survival is most likely achieved in patients who are sensitive to salvage therapy and have a complete response (CR) before ASCT, while outcome is poor in patients with residual disease. Although CD30-directed chimeric antigen receptor (CAR30) T-cell therapy induces high response rates in these patients, the duration of response is limited. Methods: We conducted an open-label, single-center and single-arm pilot study to explore the safety and efficacy of ASCT in tandem with CAR30 T-cell infusion in r/r CD30+ lymphoma (Chinese Clinical Trial Registry, number ChiCTR 2100053662). Patients will receive BEAM as preconditioning. HSCs are infused at day zero and followed by the infusion of 3rd generation CAR30 T cells in the next week. Between June 1, 2019 to May 1, 2021, 6 patients enrolled, including 5 with cHL and 1 with anaplastic lymphoma kinase-negative anaplastic large cell lymphoma (ALCL). The median age was 24 years. No patient had a prior history of ASCT. Three patients (50.0%) relapsed ≥ 2 times and 3 patients (50.0%) had primary refractory diseases. All had a Deauville score of 4 or 5, and 5 patients (83.3%) had a stable or progressive disease (SD/PD) to previous treatments at enrollment. Results: CD34+ cells were infused at day zero with a median dosage of 3.9 (IQR, 3.2-6.1) × 106 /kg and followed by the infusion of CAR30 T cells with a median dosage of 7.6 (IQR, 5.5-9.7 ) ×106 /kg at +2 to +6 days. Cytopenias represented the most commonly severe advers events (≥ grade 3). The engraftments of neutrophil or platelet occured at a median time of 13.5 (IQR,12.3-14.0 ) days or 11.5 (IQR, 11.0-12.8) days, respectively, suggesting rapid multilineage engraftments post-ASCT. Cytokine release syndrome (CRS) was observed in 5 (83.3%) patients, all of which were grade 1. No neurotoxicity or severe infection was observed. At month 3 after HSC infusion, all patients achieved objective responses, including 5 (83.3%) with a CR and 1 with a patial response (PR). With a median follow-up of 18.2 (range, 9.9-32.1) months, the median PFS and OS were not reached. At January 31, 2022, the data-cutoff date, all patients maintained their responses and remained alive without disease relapse or progression. Of note, responses were sustained in all 5 patients who had a SD/PD at enrollment. Conclusions: Our work demonstrates tandem administration of ASCT and CAR30 T-cell therapy was well-tolerated and highly active in r/r HL and ALCL, even in PET-positive or chemorefractory patients who were expected to have inferior outcome after ASCT, although further large-scale validation in prospective clinical trial is warranted. Clinical trial information: ChiCTR2100053662.

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Abstract Details

Meeting

2022 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia

Track

Hematologic Malignancies

Sub Track

Cell Therapy, Bispecific Antibodies, and Autologous Stem Cell Transplantation for NHL, HL, or CLL

Clinical Trial Registration Number

ChiCTR2100053662

Citation

J Clin Oncol 40, 2022 (suppl 16; abstr 7532)

DOI

10.1200/JCO.2022.40.16_suppl.7532

Abstract #

7532

Poster Bd #

186

Abstract Disclosures

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