TY - JOUR
T1 - Transient responses and significant toxicities of anti-CD30 CAR T cells for CD30+ lymphomas
T2 - results of a phase 1 trial
AU - Brudno, Jennifer N.
AU - Natrakul, Danielle A.
AU - Karrs, Jeremiah
AU - Patel, Nisha
AU - Maass-Moreno, Roberto
AU - Ahlman, Mark A.
AU - Mikkilineni, Lekha
AU - Mann, Jennifer
AU - Stroncek, David F.
AU - Highfill, Steven L.
AU - Fromm, Genevieve C.
AU - Patel, Rashmika
AU - Pittaluga, Stefania
AU - Kochenderfer, James N.
N1 - Publisher Copyright:
© 2024 American Society of Hematology. All rights reserved.
PY - 2024/2/13
Y1 - 2024/2/13
N2 - New treatments are needed for relapsed and refractory CD30-expressing lymphomas. We developed a novel anti-CD30 chimeric antigen receptor (CAR), designated 5F11-28Z. Safety and feasibility of 5F11-28Z-transduced T cells (5F11-Ts) were evaluated in a phase 1 dose escalation clinical trial. Patients with CD30-expressing lymphomas received 300 mg/m2 or 500 mg/m2 of cyclophosphamide and 30 mg/m2 of fludarabine on days -5 to -3, followed by infusion of 5F11-Ts on day 0. Twenty-one patients received 5F11-T infusions. Twenty patients had classical Hodgkin lymphoma, and 1 had anaplastic large-cell lymphoma. Patients were heavily pretreated, with a median of 7 prior lines of therapy and substantial tumor burden, with a median metabolic tumor volume of 66.1 mL (range, 6.4-486.7 mL). The overall response rate was 43%; 1 patient achieved a complete remission. Median event-free survival was 13 weeks. Eleven patients had cytokine release syndrome (CRS; 52%). One patient had grade 3 CRS, and there was no grade 4/5 CRS. Neurologic toxicity was minimal. Nine patients (43%) had new-onset rashes. Two patients (9.5%) received extended courses of corticosteroids for prolonged severe rashes. Five patients (24%) had grade 3/4 cytopenias, with recovery time of 30 days, and 2 of these patients (9.5%) had prolonged cytopenias with courses complicated by life-threatening sepsis. The trial was halted early because of toxicity. Median peak blood CAR+ cells per μL was 26 (range, 1-513 cells per μL), but no infiltration of CAR+ cells was detected in lymph node biopsies. 5F11-Ts had low efficacy and substantial toxicities, which limit further development of 5F11-Ts. This trial was registered at www.clinicaltrials.gov as #NCT03049449.
AB - New treatments are needed for relapsed and refractory CD30-expressing lymphomas. We developed a novel anti-CD30 chimeric antigen receptor (CAR), designated 5F11-28Z. Safety and feasibility of 5F11-28Z-transduced T cells (5F11-Ts) were evaluated in a phase 1 dose escalation clinical trial. Patients with CD30-expressing lymphomas received 300 mg/m2 or 500 mg/m2 of cyclophosphamide and 30 mg/m2 of fludarabine on days -5 to -3, followed by infusion of 5F11-Ts on day 0. Twenty-one patients received 5F11-T infusions. Twenty patients had classical Hodgkin lymphoma, and 1 had anaplastic large-cell lymphoma. Patients were heavily pretreated, with a median of 7 prior lines of therapy and substantial tumor burden, with a median metabolic tumor volume of 66.1 mL (range, 6.4-486.7 mL). The overall response rate was 43%; 1 patient achieved a complete remission. Median event-free survival was 13 weeks. Eleven patients had cytokine release syndrome (CRS; 52%). One patient had grade 3 CRS, and there was no grade 4/5 CRS. Neurologic toxicity was minimal. Nine patients (43%) had new-onset rashes. Two patients (9.5%) received extended courses of corticosteroids for prolonged severe rashes. Five patients (24%) had grade 3/4 cytopenias, with recovery time of 30 days, and 2 of these patients (9.5%) had prolonged cytopenias with courses complicated by life-threatening sepsis. The trial was halted early because of toxicity. Median peak blood CAR+ cells per μL was 26 (range, 1-513 cells per μL), but no infiltration of CAR+ cells was detected in lymph node biopsies. 5F11-Ts had low efficacy and substantial toxicities, which limit further development of 5F11-Ts. This trial was registered at www.clinicaltrials.gov as #NCT03049449.
UR - http://www.scopus.com/inward/record.url?scp=85185278734&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85185278734&partnerID=8YFLogxK
U2 - 10.1182/bloodadvances.2023011470
DO - 10.1182/bloodadvances.2023011470
M3 - Article
C2 - 37939262
AN - SCOPUS:85185278734
SN - 2473-9529
VL - 8
SP - 802
EP - 814
JO - Blood Advances
JF - Blood Advances
IS - 3
ER -