The prognosis of adults with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) remains dismal even at this day and age [
1,
2]. With salvage chemotherapy, only 29% (range 18 to 44%) of the patients with R/R ALL can be induced into complete remission (CR), with a median overall survival (OS) of 4 months (range 2–6 months) [
3‐
10]. Novel agents are needed to improve the therapy of R/R ALL. Blinatumomab, the first FDA-approved BiTE antibody, has been shown to extend the median survival to 7.7 months in patients with CD19+, Philadelphia chromosome (Ph)––negative R/R ALL [
11] (Table
1). Recently, inotuzumab ozogamycin (IO), a CD-22 antibody-drug conjugate, was shown to improve CR rate to 80% and overall survival to 7.7 months [
12]. In the last few years, chimeric antigen receptor (CAR)––engineered T cells have led to major progress in cancer immunotherapy [
13‐
25]. CD-19 CAR-T cells have been well studied and recently approved by FDA for children and young adults with R/R ALL (tisagenlecleucel, kymriah™) [
24,
26‐
29]. In this population of patients, 90% of the patients were induced to CR, yet the median follow-up was only 7 months. A second CD-19 directed CAR-T cell product was recently approved for the therapy of relapsed and/or refractory lymphoma (axicabtagene ciloleucel, yescarta™) [
30].
Table 1
New agents for immunotherapy of relapsed/refractory acute lymphoblastic leukemia
Phase | III | III | I | II |
Patients |
Age (year) | ≥ 18 | ≥ 18 | ≥ 18 | ≤ 21 |
No. enrolled | 271 | 141 | 83 | 92 |
No. evaluable | 267 | 109 | 53 | 75 |
Follow-up (m) | 11.7 | NA | 29 | 13.1 |
CR % | 44 | 80.7 | 83 | 81 |
EFS (m) | 7.3 | 5 (PFS) | 6.1 | NR |
OS (m) | 7.7 | 7.7 | 12.9 | NR |
CRS (≥ grade III %) | 4.9 | NA | 26 | 47 |
Neurotoxicity % | 9.4 | NA | 44 | 40 |
References | 11 | 12 | 31 | 32 |