CD19 CAR T cells are an effective therapy for posttransplant relapse in patients with B-lineage ALL: real-world data from Germany

Abstract

Patients with precursor B cell acute lymphoblastic leukemia (pB-ALL) who have relapsed subsequent to allogeneic stem cell transplantation (alloHSCT), have relapsed more than once, or are resistant upfront have a dismal prognosis. CD19-targeted CAR-T cells have evolved as potent immune therapies. Tisagenlecleucel (Tisa-cel) is a commercial autologous CD19-directed CAR-T cell product. We performed a retrospective study inviting all CAR-T cell centers in Germany to participate. Eighty-one patients with pB-ALL were included. Twenty-eight days after CAR-T cell infusion, 71 patients (87.7%) were in CR, and 8 (9.9%) were in NR. At two years, the probabilities of event-free, relapse-free and overall survival were 45.3% (pEFS), 51.7% (pRFS) and 53.2% (pOS), respectively. pEFS was not different in patients without (n=16, 55.0%) vs. with prior alloHSCT (n=65, 43.4%). In patients treated after alloHSCT, the time to relapse after alloHSCT was a strong predictor of outcome. Patients relapsing within 6 months of alloHSCT had a disappointing pEFS (pOS) of 18.4% (16.0%); pEFS (pOS) for those relapsing later was 55.5% (74.8%). Our study provides real-world experience in pediatric, adolescent and young adult patients with ALL treated with Tisa-cel, where the majority of patients were treated after having relapsed post-alloHSCT. A total of 45.3% were rescued with a single dose of Tisa-cel. Our novel finding that ALL patients post-alloHSCT had by far a better pEFS if relapse occurred beyond 6 months might be helpful in clinical decision-making and motivates studies to uncover the reasons.

Intention-to-treat outcomes utilising a stringent event definition in children and young people treated with tisagenlecleucel for r/r ALL through a national access scheme

“…The EFS for our cohort (as defined in the ELIANA study, i.e. 46.5% at 2 years) reflects that found in other real-world studies [ 6 , 9 – 11 , 22 ]. However, this only partially informs outcomes for potential CAR T-cell therapy recipients, as a significant proportion of patients need further medical intervention after tisagenlecleucel due to MRD emergence and/or loss of B-cell aplasia/CAR T-cell persistence [ 24 ].…”

“…In keeping with other paediatric real world data on CAR T therapy of ALL [ 6 , 9 , 10 , 22 ], ours was a high-risk disease cohort, with over 40% transplanted patients and 38% patients proceeding to CAR T-cell therapy with ≥5% disease. The Paediatric Real World CAR Consortium (PRWCC) cohort reported real world outcomes on delivery of tisagenlecleucel for ALL in a US context.…”

Comprehensive analysis of the efficacy and safety of CAR T-cell therapy in patients with relapsed or refractory B-cell acute lymphoblastic leukaemia: a systematic review and meta-analysis

“…Aside from haplo-HSCT transplantation, allogeneic haematopoietic stem cell transplantation (allo-HSCT) has emerged as a viable option for patients showing resistance to induction chemotherapy or experience early relapse following initial therapy [ 65 ]. A recent investigation conducted by Cao et al.…”

Chimeric Antigen Receptor (CAR) T-Cell Products for Pediatric Cancers: Why Alternative Development Paths Are Needed

“…[12][13][14] Even more remarkable, remissions in around 40% of patients treated with CAR T cells containing 4-1BB-derived costimulation have been durable without further therapy both in early-phase clinical studies 15 and in real-world databases. [16][17][18][19] It has been demonstrated that immune control of leukemia relies on the memory capacity of the CAR T cells which is reflected by persistent absence of the (CD19-positive) B-cell compartment. [16][17][18][19] Thus, single-agent CAR T cells, with preparative fludarabine and cyclophosphamide to deplete lymphocytes and allow homeostatic T-cell expansion, can cure patients for whom intensive chemotherapy, and often HSCT, has failed.…”

“…[16][17][18][19] It has been demonstrated that immune control of leukemia relies on the memory capacity of the CAR T cells which is reflected by persistent absence of the (CD19-positive) B-cell compartment. [16][17][18][19] Thus, single-agent CAR T cells, with preparative fludarabine and cyclophosphamide to deplete lymphocytes and allow homeostatic T-cell expansion, can cure patients for whom intensive chemotherapy, and often HSCT, has failed. Additionally, the toxicity profile compares favorably with conventional high-risk leukemia therapy.…”