Does AML need maintenance treatment?

Maintenance therapy is part of the standard treatment for a variety of hematological tumors, including acute lymphoblastic leukemia [ALL], acute promyelocytic leukemia [APL], and multiple myeloma [MM]
.

Maintenance therapy is not clearly defined.
It is usually given a low-intensity maintenance treatment program after induction chemotherapy and consolidation therapy
.

In acute myeloid leukemia (AML), except for APL, maintenance therapy is not a common strategy.
This may be due to the lack of relatively non-toxic and convenient options that can be used as maintenance therapy for patients with complete remission
.

Previous studies have tried to continue the standard chemotherapy regimen or use low-dose cytarabine (LDAC) as maintenance therapy to reduce the risk of disease recurrence.
Although these studies have extended the recurrence-free survival (RFS), they did not improve the overall survival (OS).
Part of the reason is because the maintenance regimen increases the toxicity of the treatment
.

At the same time, other studies have been carried out, such as a study to evaluate whether interleukin-2 (IL-2) regulates immune function can improve the potential of patients' prognosis, but it was unsuccessful due to poor tolerance
.

In another randomized trial, the combination of histamine dihydrochloride and low-dose IL-2 improved the leukemia-free survival (LFS) of patients in remission.
This study helped the combination to be approved in Europe
.

In the past ten years, with the widespread use of demethylating drugs decitabine and azacitidine, researchers have carried out a number of clinical trials for the maintenance treatment of AML
.

In a small randomized phase 2 study exploring decitabine versus traditional conventional treatment (LDAC, continued chemotherapy or supportive care), no advantage of decitabine was observed
.

Burnett et al.
also failed to prove that azacitidine maintenance treatment can improve OS relative to the control group (although azacitidine maintenance treatment does prolong RFS)
.

A CALGB study showed that decitabine maintenance treatment is feasible, but it did not improve treatment outcomes compared with historical controls
.

Recently, the HOVON team randomly assigned 116 elderly AML patients who had received 2 cycles of chemotherapy to the experimental group who received azacitidine for 1 year or the control group who did not receive any further treatment, and found that azacitidine maintenance treatment can be extended Disease-free survival (DFS), but it has no significant advantage in improving OS
.

In the QUAZAR AML-001 study, 472 patients with primary or secondary AML ≥55 years old (receiving standard induction chemotherapy with cytarabine combined with anthracyclines, with or without consolidation therapy, and unsuitable after the first remission Allogeneic hematopoietic stem cell transplantation) randomized to receive CC-486 (oral preparation of azacitidine) or placebo for 2 weeks a month
.

Most patients (approximately 80% in both groups) received at least one cycle of consolidation therapy
.

The OS of patients receiving CC486 maintenance treatment was significantly improved (median OS: 24.
7 months vs 14.
8 months, p = 0.
0009, HR 0.
69)
.

Similar advantages have been reported for RFS
.

The oral medications were well tolerated, and expected side effects included bone marrow suppression and nausea, but the health-related quality of life scores were comparable in the two groups
.

Therefore, CC486 became the first drug approved by the U.
S.
Food and Drug Administration (FDA) for the maintenance treatment of AML
.

Other drugs explored in the field of maintenance therapy for AML include FLT3 kinase inhibitors, including midoturine and sorafenib.
Sorafenib has been shown to improve the prognosis of patients with FLT3 mutations after AML transplantation.

.

With the development of many oral administration and molecular targeted drugs, maintenance therapy is likely to make great progress in the diagnosis and treatment of AML
.

Reference source: Farhad Ravandi.
2021 SOHO.
EXABS-180-AML.
Stamp "read the original text", we make progress together