The evolving role of allogeneic haematopoietic cell transplantation in the era of chimaeric antigen receptor T‐cell therapy

Abstract

Summary Chimaeric antigen receptor T‐cell (CAR T) therapy has revolutionized the management of many haematological malignancies. It is associated with impressive disease responses in relapsed or refractory high‐grade B‐cell non‐Hodgkin lymphoma (B‐NHL) and acute lymphoblastic leukaemia (B‐ALL) with durable remissions in a subset of patients. Historically, haematopoietic cell transplantation (HCT) has been the standard consolidation strategy for many of these patients who are now being treated with CAR T. Relapses are frequent after CD19 CAR T therapy in B‐ALL and consolidation with allogeneic HCT (allo‐HCT) may improve survival of patients with high‐risk disease. There appears to be a clear difference in B‐ALL outcomes between paediatric and adult patients, with the latter having a much higher risk of relapse after CAR T therapy. Late relapses are infrequent in patients with B‐NHL and consolidation with allo‐HCT may not be needed in patients who achieve a complete remission after CAR T therapy. Future registry‐based and prospective studies will hopefully provide the needed data in the future to risk‐stratify the recipients of CAR T therapy. Meanwhile, we provide guidance on patient selection and practical issues with performing allo‐HCT after CAR T therapy.

Indications for haematopoietic cell transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2022

“…Relapse after CAR-T cell therapy occurs in 30-50% of patients (with CD19 negative relapse in up to 40%) [57,61]. The question of post-CAR-T cell consolidation with allo-HCT is still open and data are controversial.…”

“…Many centres undertake allo-HCT for adult ALL patients following CAR-T cell treatment even in an MRD-negative remission. In any event, patients with molecular MRD positivity following CAR-T cell therapy, loss of B-cell aplasia and without a previous HCT are candidates for consolidative allo-HCT post CAR-T cell infusion [61].…”

Preferential expansion of CD8+ CD19-CAR T cells postinfusion and the role of disease burden on outcome in pediatric B-ALL

“…3,[6][7][8][9][10][11][12][13][14] Furthermore, at present, the optimal management for patients who achieve a complete response after CD19-CAR T-cell therapy is unknown, including which patients should proceed to consolidative allogeneic hematopoietic cell transplantation (AlloHCT). 15,16 While a commercial CD19-CAR T-cell product is available for pediatric B-ALL, there is a continued need to study new CD19.41BBζ-CAR T-cell products, with the goal of identifying improvements in manufacturing techniques, modification of construct design, and optimization of administration conditions, which result in improvements in long-term response rates. We, therefore, developed an early phase clinical study (SJCAR19; NCT03573700) to evaluate the use of autologous T cells expressing CD19.41BBζ-CARs 17 (CD19-CAR T cells) in patients ≤21 years of age with relapsed/refractory B-ALL.…”

Challenges and Advances in Chimeric Antigen Receptor Therapy for Acute Myeloid Leukemia

“…This suggests that performing SCTs in patients with MRD negative disease after CAR T-cell therapy may not be beneficial. However, we know that better remissions before allogenic SCT is indicative of prolonged survival after allogenic SCT, which makes matters more complicated especially in high-risk disease [145,146]. In a clinical trial of 58 patients with r/r B-ALL who had failed targeted CD19 therapy and were given a CD22 CAR T-cell infusion, those who achieved CR (70%) and underwent SCT had a greater EFS and OS than those who did not undergo SCT [147].…”

“…If the plan is to do a consolidative or tandem SCT, timing is critical. While most patients achieve CR within one month of CAR T-cell infusion, most relapses also occur within the first six-month window [146]. Therefore, ideally, the SCT should be performed within the first three to six months after CAR-T cell infusion after CAR T associated side effects such as CRS/ICANs have resolved.…”