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Approximately 25% of patients with acute myeloid leukemia (AML) have internal tandem duplication of FMS-like tyrosine kinase 3 (FLT3-ITD) mutations and survival is often inferior due to high relapse rates and short remission periods.1 Since the optimal therapy is challenging for patients with FLT3-ITD AML who relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT), sorafenib, as monotherapy or in combination, has recently been suggested to be an option for salvage therapy.
Li Xuan, from the Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, CN, and colleagues retrospectively evaluated the efficacy of sorafenib combined with other therapeutic strategies for patients with FLT3-ITD AML, who had relapsed after allo-HSCT.
Patients with FLT3-ITD mutations at relapse after allo-HSCT recruited from seven hospitals (Nanfang Hospital, Peking University People’s Hospital, First Affiliated Hospital of Soochow University, Institute of Hematology and Blood Diseases Hospital, Xinqiao Hospital, Zhujiang Hospital and First People’s Hospital of Chenzhou) were assessed retrospectively between January 2012 and October 2017.
Table 1: Patient characteristics, entire sample and sorafenib groups
|
Entire sample, |
Sorafenib, |
Non-sorafenib, |
P value |
---|---|---|---|---|
Median age at transplant, years, (range) |
36 (14—59) |
37 (15—59) |
35 (14—57) |
0.758 |
Gender |
|
|
|
0.834 |
Male |
43 (51.8%) |
27 (50.9%) |
16 (53.3%) |
|
Female |
40 (48.2%) |
26 (49.1%) |
14 (46.7%) |
|
Disease status at transplant |
|
|
|
0.677 |
CR |
58 (69.9%) |
38 (71.7%) |
20 (66.7%) |
|
PR |
7 (8.4%) |
5 (9.4%) |
2 (6.7%) |
|
NR |
18 (21.7%) |
10 (18.9%) |
8 (26.7%) |
|
Donor type |
|
|
|
0.685 |
HLA-matched sibling |
31 (37.3%) |
18 (34.0%) |
13 (43.3%) |
|
HLA-matched unrelated |
10 (12%) |
7 (13.2%) |
3 (10.0%) |
|
HLA-Haploidentical related |
45 (50.6%) |
28 (52.8%) |
14 (46.7%) |
|
Sorafenib use before relapse |
|
|
|
0.627 |
Use |
33 (54.1%) |
18 (51.4%) |
15 (57.7%) |
|
No use |
28 (45.9%) |
17 (48.6%) |
11 (42.3%) |
|
aGvHD before relapse |
|
|
|
0.588 |
No aGvHD |
55 (66.3%) |
34 (64.2%) |
21 (70.0%) |
|
Table 2: Patient characteristic, donor lymphocyte infusion (DLI) groups, on the basis of DLI inclusion in salvage therapy
|
DLI group |
Non-DLI group |
P value |
---|---|---|---|
Median age at transplant, years, (median) |
37 (14—57) |
35 (17—59) |
0.506 |
Gender |
|
|
0.982 |
Male |
30 (51.7%) |
13 (52.0%) |
|
Female |
28 (48.3%) |
12 (48.0%) |
|
Disease status at transplant |
|
|
0.091 |
CR |
41 (70.7%) |
17 (68.0%) |
|
PR |
7 (12.1%) |
0 (0.0%) |
|
NR |
10 (17.2%) |
8 (32.0%) |
|
Donor type |
|
|
0.481 |
HLA-matched sibling |
24 (41.1%) |
7 (28.0%) |
|
HLA-matched unrelated |
7 (12.1%) |
3 (12.0%) |
|
HLA-Haploidentical related |
27 (46.5%) |
15 (60.0%) |
|
Sorafenib use before relapse |
|
|
0.814 |
Use |
21 (55.3%) |
12 (52.2%) |
|
No use |
17 (44.7%) |
11 (47.8%) |
|
aGvHd before relapse |
|
|
*0.001 |
No aGvHD |
45 (77.6%) |
10 (40.0%) |
|
Table 3: Outcomes after salvage therapy
OS = overall survival, PFS = progression-free survival, GRFS = GvHD-free/relapse-free survival, NRM = non-relapse mortality. *P<0.05 |
||||||
|
Entire sample, |
Group A |
Group B |
Group C |
Group D |
P value |
---|---|---|---|---|---|---|
CR |
44 (53.0%) |
29 (70.7%) |
6 (50.0%) |
6 (35.3%) |
3 (23.1%) |
*0.007 |
OR |
59 (71.1%) |
36 (87.8%) |
8 (66.7%) |
10 (58.8%) |
5 (38.5%) |
*0.003 |
1-year incidence of aGvHD after salvage therapy |
32.0% (CI 22.1%—42.4%) |
39.5% (CI 24.4%—54.3%) |
29.4% (CI 9.4%—51.9% |
34.7% (CI 10.2%—62.4%) |
7.7% (CI 0.4%—30.4% |
0.242 |
1-year incidence of cGvHD after salvage therapy |
28.1% (CI 17.8%—38.3%) |
32.8% (CI 18.2%—48.3) |
27.1% (CI 5.6%—55.4%) |
35.8% (CI 8.9%—64.6%) |
0.0% |
0.276 |
1-year mortality of GvHD after salvage therapy |
3.6% (CI 1.0%—9.4%) |
2.4% (CI 0.2%—11.2%) |
8.3% (CI 0.3%—33.7%) |
5.9% (CI 0.3%—25.1%) |
0.0% |
0.662 |
1-year OS |
37.2% (CI 26.8%—47.5%) |
53.2% (CI 36.9%—67.1%) |
25.0% (CI 6.0%—50.5%) |
23.5% (CI 7.3%—44.9%) |
15.4% (CI 2.5%—38.8%) |
*0.003 |
1-year PFS |
34.7% (CI 24.7%—45.0%) |
50.8% (CI 34.6%—64.9%) |
25.0% (CI 6.0%—50.5%) |
23.5% (CI 7.3%—44.9%) |
7.7% (CI 0.5%—29.2%) |
*<0.001 |
1-year GRFS |
30.2% (CI 20.6%—40.4%) |
41.8% (26.3%—56.6%) |
25.0% (6.0%—50.5%) |
23.5% (7.3%—44.9%)
|
7.7% (0.5%—29.2%) |
*0.018 |
1-year NRM |
15.7% (CI 8.8%—24.3%) |
12.4% (CI 4.4%—24.7%) |
25.0% (CI 5.0%—52.6%) |
23.5% (CI 6.7%—46.1%) |
15.4% (CI 2.1%—40.5%) |
0.763 |
The study found that salvage therapy containing sorafenib was superior with regards to OS, PFS, and GRFS for patients with FLT3-ITD AML. Results showed that salvage therapy with sorafenib combined with chemotherapy followed by DLI improved OS and PFS, over chemotherapy alone, chemotherapy followed by DLI and chemotherapy combined with sorafenib. The results indicate that the induction of graft-versus-leukemia effect through allogenic immune cells can be enhanced by sorafenib.
The number of patients in the study was relatively small, and as the data was assessed retrospectively, well-designed clinical trials are necessary to establish whether sorafenib therapy, combined with chemotherapy and followed by DLI, would result in optimal outcomes for patients.
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