The clinical landscape for CAR-T, and current developments in Europe
The clinical landscape for CAR-T, and current developments in Europe were the focus of several presentations. Individual sessions were devoted to key indications for CAR T-cell therapy such as acute leukemia, myeloma, and lymphoma, and further examined the latest preclinical and clinical data in the CAR-T domain.
Click on the titles below to read more and view the presentations (if available).
CD30 memory T cells for Hodgkin and T cell lymphoma (Javier Briones, Spain)
Dr Briones presented research indicating that highly enriched memory stem CAR-T can be efficiently transduced with a CAR30 and expanded ex vivo. Products demonstrate significant antitumor activity both in vitro and in vivo for Hodgkin and CD30+ T cell lymphoma as well as high persistence in vivo, conferring long-lasting immunity against Hodgkin lymphoma.
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L1CAM-specific CAR T-cell therapy for childhood neuroblastoma: Engineered Neuroblastoma Cellular ImmunoTherapy (ENCIT)-01 (Annette Künkele, Germany)
L1CAM-specific CAR T-cells manufactured from patients with relapsed/refractory neuroblastoma. were able to infiltrate tumors, with stable disease achieved in 18% of patients (3/17) and pseudo-progression in 29% (5/17). Transient T cell-related toxicity was observed including rash (41%) and hyponatremia (12%).
iPSC CARs (Maria Themeli, The Netherlands)
Induced pluripotent stem cell (iPSCs) are a source of functional CAR T-cells and natural killer (NK) cells that can be genetically modified to produce desirable characteristics. Clinical application of iPSC NK cells has begun but challenges remain. Advances in genome engineering may also help to streamline the process and could ultimately lead to ‘off-the-shelf’ lymphocytes for the treatment of cancer.
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Post-transplant relapse-Second SCT or CAR T-cells (Peter Bader, Germany)
CAR-T therapy is an option for pediatric relapsed/refractory B-cell ALL (B-ALL). In 24 patients treated with CAR T-cells following Stem Cell Transplant (SCT), CAR T-cell therapy was well tolerated, and survival rates cells were better compared to rescue therapy with a second allogeneic SCT.
B-cell aplasia (Andre Baruchel, France)
Early B-cell recovery due to lack of persistence of CAR-T is associated with relapse, and early diagnosis with strict monthly monitoring is critical. 37% of patients with advanced B-ALL lost B-cell aplasia (BCA) at 6 months and 9/17 of these experienced a leukemic event. Co-stimulation signaling (CD28 vs 4-1BB+++) is a major factor for poor T-cell expansion and /or persistence. The CAPTiRALL trial assesses the effect of anti-PD1 antibody with tisagenlecleucel reinfusion to limit loss of persistence.
Cytopenia (Marion Subklewe, Germany)
Cytopenia (neutropenia) is the most common adverse event reported in CAR-T clinical trials, across all diseases and CAR-T constructs. Cytopenia can be biphasic (early: 80% of patients, late: 30-40% of patients). Prolonged cytopenia (>90 days) occurs in 8-18% of patients and can last for at least 1-year post-treatment. The need for antimicrobial prophylaxis needs to be considered.
Disease and age groups (Marie José Kersten, The Netherlands)
CAR-T can be used in specific subgroups of patients with DLBCL. There is no increase in toxicity in optimally selected patients >65 years when compared to the general patient population. CAR-T can be cautiously used in patients with hepatitis C, with adequate prophylaxis. Experience remains limited in patients with CNS disease. Further trials and real-world data are needed.
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Guidelines (Ibrahim Yakoub-Agha, France)
The European society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EMBT (JACIE) published guidelines providing practical and clinically relevant recommendations for CAR-T treatment, from planning to delivery. Key topics covered include eligibility, laboratory work-up, apheresis, bridging and conditioning, complication management and long-term follow-up.