CD19-directed CAR T cell therapy for patients with relapsed or refractory chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) usually follows an indolent course without affecting life expectancy and quality of life to a relevant extent. However, in a small minority of patients the disease behaves aggressively and develops resistance against modern drugs such as Bruton tyrosine kinase inhibitors (BTKi, e.g. acalabrutinib and zanubrutinib) and BCL-2 inhibitors (BCL2i, e.g. venetoclax). These so called double-refractory patients could benefit from CAR T cell therapy.

CAR T-cells are immune cells that are genetically engineered to recognize specific structures on the surface of cancer cells. This enables CAR T-cells to kill cancer cells. Unlike drug-based CLL treatments, CAR T-cell therapy is always a one-hit treatment, meaning that after an approximately two-week inpatient treatment and monitoring period (optional partly outpatient), the actual therapy is completed. However, outpatient follow-up care is provided to monitor tolerability and treatment efficacy according to a structured schedule.

CD19 CAR T-cell products manufactured by industry are approved in Europe for several other leukemias and cancers of the immune system. CAR T-cells for CLL, however, are available in Germany outside of clinical trials only at Heidelberg University Hospital.

Our CAR T-cell product is heidagen-lecleucel, a novel CD19-directed CAR T-cell product that has demonstrated excellent tolerability and promising efficacy in patients with advanced CLL. It is manufactured at Heidelberg University Hospital and is authorized by Germany’s federal competent authority, the Paul-Ehrlich-Institut, for use in adult patients with CLL.

Treatment decisions are made on the basis of an individual medical assessment. In general, CAR T-cell therapy for CLL is considered only after the available approved drug-based treatment options have been largely exhausted and allogeneic stem cell transplantation is not an option.

Accordingly, the all of following eligibility criteria must be met:

• Relapsed or refractory CLL

• Lack of response to covalent BTKi (ibrutinib, acalabrutinib, zanubrutinib)

• Lack of response to, or early relapse (within 2 years after end of treatment) following BCL2i (venetoclax, sonrotoclax)

• No transformation of CLL into an aggressive non-Hodgkin or Hodgkin lymphoma

• Good performance status (ECOG 0–1)

Additional note: Further medical requirements (e.g., comorbidities, organ function, infection status, disease activity, concomitant medication) are reviewed individually.

The Heidelberg CLL CAR T cell program is led by Prof. Dr. Peter Dreger and Prof. Dr. Michael Schmitt, two internationally renowned experts in cellular therapy for CLL and in the in-house manufacturing of CAR T cells, respectively. Supported by a dedicated team of physicians, scientists, case managers, nursing staff, and laboratory specialists, they will advise you on eligibility and the optimal timing for CAR T cell therapy, discuss treatment alternatives, guide you through the treatment process and follow-up care. 

Your coordinator and primary contact throughout your CAR T-cell journey is Dr. Patrick Derigs, an experienced cellular therapy specialist.