CAR T-Cell Therapy for Relapsed/Refractory B-Cell Malignancies: Promising Results from Indian Phase 1/2 Trial
Mumbai, India – A groundbreaking phase 1/2 study published in The Lancet Haematology has reported promising outcomes for talicabtagene autoleucel, a novel humanized anti-CD19 4-1BB chimeric antigen receptor (CAR) T-cell therapy, in patients with relapsed or refractory B-cell malignancies in India. Conducted across six tertiary cancer centers, the study highlights both the safety and efficacy of this therapy, marking a significant advancement for cancer treatment in low- and middle-income countries (LMICs).
Study Overview
In LMICs, relapsed or refractory B-cell malignancies have poor outcomes due to the lack of effective treatment options. This open-label, multicenter trial aimed to evaluate the safety and efficacy of talicabtagene autoleucel. Phase 1, conducted at Tata Memorial Hospital, included patients aged 18 years and older with relapsed or refractory B-cell lymphomas. Phase 2 expanded to five additional centers and included patients aged 15 years and older with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) or B-cell lymphoma.
Eligible patients underwent apheresis to collect lymphocytes for CAR T-cell manufacturing, followed by lymphodepletion with cyclophosphamide and fludarabine or bendamustine. Patients then received intravenous infusions of talicabtagene autoleucel.
Key Findings
- Safety: The treatment demonstrated a manageable safety profile, with no cases of immune effector cell-associated neurotoxicity syndrome (ICANS). Grade 3+ cytokine release syndrome (CRS) was rare, but immune-effector cell-associated hemophagocytic lymphohistiocytosis (IEC-HS) occurred in 12% of patients, leading to one fatality. Hematological toxicities such as neutropenia (96%), thrombocytopenia (65%), and febrile neutropenia (47%) were the most common severe side effects. Two treatment-related deaths were reported.
- Efficacy: Among 51 efficacy-evaluable patients (36 with B-cell lymphoma, 15 with B-ALL), the overall response rate (ORR) was 73% (95% CI 59–83), demonstrating significant clinical benefit.
Clinical Implications
The results underscore the potential of CAR T-cell therapy as a viable treatment option for relapsed or refractory B-cell malignancies in India. Given the high response rate and manageable toxicity, this therapy addresses a critical unmet need for patients in LMICs, where access to advanced cancer treatments remains limited.
Future Directions
While the study provides a strong foundation for CAR T-cell therapy in India, researchers emphasize the need for faster and more effective management strategies for IEC-HS and severe hematological toxicities. Further trials and real-world implementation studies will be crucial to refining treatment protocols and expanding accessibility.
Funding and Correspondence
The study was supported by Immunoadoptive Cell Therapy (ImmunoACT) and the Indian Council of Medical Research (ICMR). Correspondence regarding the trial can be directed to Dr. Rahul Purwar at ImmunoAdoptive Cell Therapy (ImmunoACT), Mumbai.
This landmark trial paves the way for broader adoption of CAR T-cell therapies in India and other LMICs, offering new hope to patients battling aggressive B-cell malignancies.
