Case expert evaluation Professor Liu Qiqi: Breaking through the clouds, girutinib helps patients with relapsed FLT3 mutation AML transplantation to benefit, and the whole process of FLT3 mutation AML is managed like a tiger

AML is the most common type of adult leukemia and is a rapidly progressive and heterogeneous hematologic malignancy
.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potential treatment to cure most intermediate- and high-risk AMLs
.
However, even with allo-HSCT, there is a high rate of recurrence after transplantation and is associated with a very poor prognosis1
.
In particular, relapse is a leading cause of death 100 days after allogeneic hematopoietic stem cell ^{transplantation1}
.
Treatment is very limited
for patients with AML who have relapsed after transplantation, especially those who are using the FLT3 mutation of sorafenib before and after transplantation.

In recent years, the emergence of the FLT3 inhibitor gemitinib has shaken the choice of
FLT3 mutant R/R AML regimen.
The effectiveness of geratinib in patients with R/R AML with FLT3 MUTATIONS has been demonstrated in both ADMIRAL and COMMODORE ^studies2-3 The phase III ADMIRAL study showed that the treatment of FLT3 mutant R/R AML with geratinib significantly prolonged median overall survival (OS, 9.
3 vs.
5.
6 months; HR: 0.
64; 95% CI: 0.
49, 0.
83; P<0.
001); NEW RESULTS FROM THE MULTICENTER PHASE III COMMODORE STUDY IN CHINA AND OTHER ASIAN COUNTRIES ALSO SHOWED THAT GERATINIB NEARLY DOUBLED THE MEDIAN OS IN R/R AML PATIENTS WITH FLT3 MUTATIONS (9.
0 vs.
4.
7 months; HR: 0.
549；95% CI: 0.
379, 0.
795；P=0.
00126）<b21>。 Furthermore, a retrospective study including the CHRYSALIS study and the ADMIRAL study showed that geratinib still had up to 52% efficacy against FLT3-mutant R/R AML patients who had previously received FLT3 inhibitors such as sorafenib (42%, CHRYSALIS study; 52%, ADMIRAL study) ⁴
.
As for the efficacy of R/R AML maintenance therapy with FLT3 mutations, GOSSAMER ^STUDY5 ALSO SHOWED THAT THE MEDIAN RECURRENCE-FREE SURVIVAL (RFS) IMPROVEMENT IN GERATINIB MAINTENANCE THERAPY FOR FLT3-ITD MUTANT R/R AML was better than that in the placebo group (24.
02 vs.
15.
84 months; HR: 0.
738；95% CI: 0.
407, 1.
336；P=0.
163）； ADMIRAL phase III follow-up ^data6 showed that the 2-year recurrence rate of r/R AML patients after transplantation of giretinib maintenance therapy was only 19%; Another ^study7 demonstrated that patients treated with giratinib maintenance after transplantation had significantly longer median OS than those not treated with giratinib maintenance (16.
2 vs.
8.
4 months; HR: 0.
387；95% CI: 0.
164, 0.
915）
。 In addition, the frequency of grade 3 and above adverse events was low (19.
34 versus 42.
44 times/year), and the most common grade 3 or higher adverse events were febrile neutropenia (45.
9%), anemia (40.
7%), and thrombocytopenia (22.
8%), with a good safety ^profile2-7
.

The patient in this case was AML with FLT3-ITD mutation, and the MRD was negative after chemotherapy combined with sorafenib treatment before transplantation, and the intermittent sorafenib maintenance therapy after transplantation still had post-transplant recurrence, and was induced and consolidated by giretinib combined with chemotherapy, and hiratinib survived without disease after maintenance therapy
.
This is a successful case
of a geratinib-containing regimen for the treatment of relapsed FLT3-ITD mutant AML after transplantation.
One course of regimen containing geratinib can clear FLT3-ITD mutations, and persistent MRD negative after consolidation and maintenance therapy, which shows that geratinib has great potential
in induction, consolidation, and maintenance therapy.
An international multicenter, randomized, double-blind phase III morpho study of 356 patients on post-transplant maintenance therapy with R/R AML with FLT3 mutations has also been conducted to compare the efficacy and safety
of generatinib versus placebo after receiving allo-HSCT.
It is believed that in the future, girutinib will be able to help more and more patients obtain better survival benefits in the whole process of FLT3 mutation R/R AML management!

Professor Liu Qiqi

• Dean of the Institute of Hematology and Director of the Institute of Hematology, Southern Medical University

• Director of the Department of Hematology, Professor, Chief Physician and Doctoral Supervisor of Nanfang Hospital

• Member of the Asia-Pacific Society of Hematology

• Vice Chairman of the Hematology Branch of the Chinese Medical Association

• Head of the Infectious Disease Group of the Hematology Branch of the Chinese Medical Association

• Vice President of Hematology Branch of Chinese Geriatrics Association

• Vice Chairman of the Cell Research and Therapy Branch of the Chinese Research Hospital Association

• Member of the Standing Committee of Hematologist Branch of Chinese Medical Doctor Association

• Chairman of the Hematology Branch of Guangdong Medical Association and Vice Chairman of the Society of Cell Therapy

• Chief expert of hematological oncology in Guangdong Province

References:

1.
Wang D, Sun Z, Zhu X, et al.
Blood.
2022 Aug 18:blood.
2022015474.

2.
Perl AE, Martinelli G, Cortes JE, et al.
N Engl J Med.
2019 Oct 31; 381(18):1728-1740.
.

3.
Wang JX, Jiang B, Li J, et al.
Poster on EHA 2022 (P554).

4.
Perl AE, Hosono N, Montesinos P, et al.
Blood Cancer J.
2022 May 30; 12(5):84.

5.
Mark D.
Minden, Jacob M.
et, al.
Cancer Res 15 June 2022; 82 (12_Supplement): CT537.

6.
Perl AE, Larson RA, Podoltsev NA, et al.
EHA Library.
J.
Levis M.
06/09/21; 325192; EP438.

7.
Maeda Y, Hosono N, Yokoyama H, et al.
EHA Library.
E Perl A.
06/09/21; 325195; EP441.

Edit: May