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Patients with acute lymphoblastic leukemia (ALL) who do not respond to chemotherapy and relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) have a poor prognosis. Novel cellular immunotherapies, such as CD19-directed chimeric antigen receptor (CAR) T cells, are being investigated for this high-risk patient population. The efficacy of CAR T-cell therapy has been confirmed in large studies of patients with precursor relapsed and refractory (R/R) B-cell ALL (B-ALL).
Here, we summarize a real-world retrospective study involving CAR T-cell centers in Germany that were approved to perform treatment with tisagenlecleucel (tisa-cel). The centers were asked to collect treatment data reflecting post-approval reality to verify clinical trial outcome data. In addition, the study aimed to identify patients who would benefit most from this tisa-cel treatment.1
The study was conducted between September 1, 2018, and January 1, 2022. Included patients had B-ALL, received tisa-cel, were aged ≤25 years, and had primary refractory disease, ≥2 relapses, or had relapsed after allo-HSCT.
A total of 81 patients were included and the baseline characteristics were similar between patients with/without prior allo-HSCT (Table 1).
Table 1. Patient characteristics*
Characteristic, % (unless otherwise stated) |
All patients |
With HSCT |
Without HSCT |
---|---|---|---|
Median age (range), years |
11.5 (1–25) |
10 (1–25) |
14.5 (1.2–25) |
Female |
34.6 |
35.4 |
31.2 |
Male |
65.4 |
64.6 |
68.8 |
Preliminary treatment |
|||
Primary refractory |
1.2 |
0.0 |
6.2 |
Relapsed refractory |
18.5 |
0.0 |
93.8 |
HSCT |
80.2 |
100.0 |
NA |
Cytogenetics |
|||
Favorable |
13.6 |
10.8 |
25.0 |
Intermediate risk |
50.6 |
50.8 |
50.0 |
High risk |
35.8 |
38.5 |
25.0 |
Remission status at LDC |
|||
<5% blasts |
54.3 |
50.8 |
68.8 |
≥5% blasts |
45.7 |
49.2 |
31.2 |
HSCT, hematopoietic stem cell transplantation; LDC, lymphodepleting chemotherapy; NA, not applicable. |
The results showed that patients with refractory or relapsed disease, including patients who relapsed after allo-HSCT, could be rescued with a single infusion of CAR T cells.
Figure 1. Response rates at 28 days post-CAR T-cell infusion*
CAR, chimeric antigen receptor; CR, complete response; NR, no response.
*Adapted from Bader, et al.1
Of the 81 patients involved in this study, 65 had received a prior allo-HSCT for high-risk or relapsed disease, and subsequently relapsed before receiving CAR T-cell therapy. With a relatively a high proportion of patients having received allo-HSCT, this was a unique population in real-world evidence and was therefore analyzed in detail.
Patients who relapsed within 6 months of receiving an allo-HSCT had a median follow-up of 28.8 months; they also had a lower pEFS compared with those relapsing more than 6 months after allo-HSCT. Furthermore, pOS and pRFS were lower in patients who relapsed within 6 months of allo-HSCT compared with patients who relapsed more than 6 months following allo-HSCT. Treatment failure was mainly due to relapse, with the cumulative incidence of relapse being higher for patients who had relapsed within 6 months of allo-HSCT compared with those who had relapsed beyond 6 months (68.5% vs 37.1%; p = 0.026). A comparison between pEFS, pOS, PRFS, and cumulative incidence of relapse is shown in Figure 2.
Figure 2. Response rates for patients who relapsed within and beyond 6 months after allo-HSCT*
Allo-HSCT, allogeneic hematopoietic stem cell transplantation; CIR, cumulative incidences of relapse; pEFS, probability of event-free survival; pOS, probability of overall survival; pRFS, probability of relapse-free survival.
*Adapted from Bader, et al.1
This real-world study demonstrated promising outcomes with tisa-cel in patients with R/R B-ALL. The results showed that patients who relapsed after allo-HSCT could be rescued with a single infusion of tisa-cel. Furthermore, patients who relapsed ≥6 months after HSCT had improved survival outcomes with a single tisa-cel infusion and no further consolidation. Prospective studies should be undertaken to further elucidate how to improve outcomes in patients who relapse during the first 6 months after allo-HSCT.
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