Prognostic exploration of adult R/R B-ALL patients who progressed after CD19 CAR-T treatment

In recent years, targeting CD19 chimeric antigen receptor (CAR) T cell therapy has changed the treatment pattern of relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL)
.

A number of previous studies have shown that CD19 CAR-T cell therapy has excellent anti-leukemia activity and high complete remission (CR) rate in B-ALL patients.
Based on this, the US FDA approved a CD19 CAR-T cell product Tisagenlecleucel is used to treat R/R B-ALL in children and adults
.

However, in adult R/R B-ALL patients, the incidence of serious adverse events (SAE) related to CAR-T cell therapy is higher.
Although the initial remission rate is higher, 10%-30% of patients have a higher incidence of CAR-T cell therapy.
T cell therapy is resistant, and 30%-60% of patients relapse after CD19 CAR-T cell therapy
.

The management of R/R B-ALL patients after CD19 CAR-T cell therapy is facing severe challenges, and the treatment and prognostic data of these patients are limited
.

Therefore, some researchers comprehensively analyzed and described in detail the clinical characteristics, follow-up treatment and prognosis of adult B-ALL patients who have progressed after receiving CD19 CAR-T cell therapy at Memorial Sloan Kettering Cancer Center (MSKCC)
.

Research methods Researchers previously reported the results of a single-center, phase I clinical study of MSKCC using CD19 (19-28z) CAR-T cell therapy to treat adult R/R B-ALL
.

The researchers described the patients in the study in detail, including the treatment before and after CAR-T cell therapy, the curative effect of the advancement rescue treatment after CAR-T cell therapy, and the patients who progressed after CAR-T cell therapy.
The prognosis; the deadline for data analysis is December 31, 2019
.

Salvage therapy after CAR-T cell therapy is divided into intensive therapy or non-intensive therapy.
Intensive therapy includes multi-drug chemotherapy with or without tyrosine kinase inhibitor (TKI); non-intensive therapy includes with or without TKI Immunotherapy, such as Blinatumomab or Inotuzumab Ozogamicin
.

Research results 1.
Outcome of patients receiving CD19 CAR-T cell therapy From May 2010 to March 2017, 56 adult R/R B-ALL patients received 19-28z CAR-T cell therapy in MSKCC, 54 cases ( 96%) patients can be evaluated for efficacy, 45 patients (83.
3%) achieved complete remission (CR), 35 patients were negative for minimal residual disease (MRD), 8 patients had measurable MRD, 2 patients had unknown MRD status, and 9 patients Ineffective for treatment
.

The incidence of severe cytokine release syndrome (CRS) and immune effector cell-related neurotoxicity syndrome (ICANS) were 27% and 43%, respectively.
Among them, 20 patients (36%) received tocilizumab treatment.
The median time from CAR-T cell infusion to tocilizumab administration was 7 days; 19 patients (34%) received corticosteroid therapy, the median time from CAR-T cell infusion to corticosteroid administration For 8 days
.

The median follow-up time was 44.
7 months, and 38 patients (68%) relapsed after CAR-T cell therapy
.

The median overall survival (OS) of the entire cohort was 13 months
.

The 3-year event-free survival (EFS) rate and OS rate were 16.
1% (95% CI: 8.
8%-29%) and 26.
6% (95% CI: 17%-42%).
The 1-year cumulative recurrence rate was 67.
9% ( 95% CI: 53.
6%-78.
6%)
.

2.
Factors related to progression after CD19 CAR-T cell therapy.
The median time to progression from CAR-T cell therapy for patients with CAR-T cell therapy is 5.
5 months, and the median survival time after CAR-T cell therapy progresses is 7.
4 months
.

High tumor burden during CAR-T cell infusion (bone marrow blasts ≥5% or extramedullary disease) is the only factor significantly associated with a higher risk of progression after CAR-T cell therapy (HR: 2.
2, 95% CI: 1.
1 -4.
4, P=0.
02)
.

3.
Rescue treatment and results of patients who progressed after CD19 CAR-T cell therapy Among the 38 patients who progressed after CAR-T cell therapy, 8 patients (21%) received only palliative corticosteroids or supportive therapy
.

Of the 30 patients (79%) who received salvage treatment, 13 patients (43%) achieved CR, but the duration of remission was short
.

It is worth noting that 7/12 patients (58.
3%) reached CR after being given belintoxumab and/or Inotuzumab Ozogamicin after CAR-T cell therapy failed
.

Multivariate analysis showed that the longer duration of sustained remission in patients after CAR-T cell therapy is related to the higher OS rate after CAR-T cell therapy progresses
.

Research conclusions In summary, the overall prognosis of adult B-ALL patients who progressed after CD19 CAR-T cell therapy is poor.
Although some patients have achieved CR through rescue treatments including belintouzumab and/or Inotuzumab Ozogamicin, the duration is Shorter
.

New treatment strategies are still needed to reduce the risk of progression after CAR-T cell therapy and improve the prognosis of these patients
.

References: Kitsada Wudhikarn, Jessica R Flynn, Isabelle Rivière, et al.
Interventions and Outcomes of Adult Patients with B-ALL Progressing After CD19 Chimeric Antigen Receptor T Cell Therapy.
Blood.
2021 Apr 13;blood.
2020009515.
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