Optimizing maintenance therapy in acute myeloid leukemia: where do we stand in the year 2024?

ABSTRACT

Introduction

Despite the prognosis of patients affected by acute myeloid leukemia (AML) improved in the last decade, most patients relapse. Maintenance therapy after a chemotherapy approach with or without allogeneic stem cell transplantation could be a way to control the undetectable residual burden of leukemic cells. Several studies are being carried out as maintenance therapy in AML. Some critical points need to be defined, how the physician can choose among the various drugs available.

Areas covered

This reviewdiscusses the advances and controversies surrounding maintenance therapy forAML patients.

Expert opinion

Patients withFLT3-positive AML should receive midostaurin or quizartinib in the first-linesetting. For a patient initially receiving midostaurin, consider switching tosorafenib in the post-transplant setting. Because of the improved safetyprofile and potency, many experts will lean toward using a second-generationFLT3 inhibitor such as quizartinib or gilteritinib. Finally, no data indicatewhether maintenance therapy should be prolonged until progression or for adefined period.

KEYWORDS:

• Acute myeloid leukemia
• relapse
• measurable residual disease
• maintenance therapy

Disclaimer

As a service to authors and researchers we are providing this version of an accepted manuscript (AM). Copyediting, typesetting, and review of the resulting proofs will be undertaken on this manuscript before final publication of the Version of Record (VoR). During production and pre-press, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal relate to these versions also.

Article highlights

• Development of maintenance therapy with the use of FLT3 inhibitors post allo-SCT.

• Promising results obtained from the IDH inhibitors ivosidenib and enasidenib.

• Several other approaches are being explored, including novel targeted agents, immunotherapy, and CAR T-cell to improve the outcomes of AML.

• Patients with FLT3-positive AML should receive MIDO or QUIZA in the first-line setting.

• Several maintenance treatment approaches based on HMAs, and targeted small molecules have been explored in AML.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One reviewer has received consulting fees, research fees, or honorarium from Jazz, Abbvie, BMS, and Aptitude health. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

AML, acute myeloid leukemia; Aza, azacitidine; BM, bone marrow; CMML, chronic myelomonocytic leukemia; CR, complete response; CRi, complete response with incomplete blood count recovery; CT, chemotherapy; ECOG, Eastern Cooperative Oncology Group; f/u, follow-up; MDS, myelodysplastic syndromes; OS, overall survival; PS, performance status; RFS, relapse-free survival; tx, treatment.

AE, adverse event; Aza, azacitidine; Gr, grade; TEAE, treatment-emergent adverse event; URTI, upper respiratory tract infection.

AlloHSCT, allogeneic hematopoietic stem cell transplant; AML, acute myeloid leukemia; APL, acute promyelocytic leukemia; CR, complete response; CRc, composite complete response; CT, chemotherapy; DoCR, duration of complete response; ECOG, Eastern Cooperative Oncology Group; EFS, event-free survival; HiDAC, high-dose cytarabine; MRD, measurable residual disease; OS, overall survival; PS, performance status; RFS, relapse-free survival; RT, radiotherapy; WBC, white blood cell.

AML, acute myeloid leukemia; Aza, azacitidine; BM, bone marrow; CMML, chronic myelomonocytic leukemia; CR, complete response; CRi, complete response with incomplete blood count recovery; CT, chemotherapy; ECOG, Eastern Cooperative Oncology Group; f/u, follow-up; MDS, myelodysplastic syndromes; OS, overall survival; PS, performance status; RFS, relapse-free survival; tx, treatment.

AE, adverse event; Aza, azacitidine; Gr, grade; TEAE, treatment-emergent adverse event; URTI, upper respiratory tract infection.

allo-SCT, allogeneic stem cell transplant; AML, acute myeloid leukemia; APL, acute promyelocytic leukemia; CR, complete response; CRc, composite complete response; CT, chemotherapy; DoCR, duration of complete response; ECOG, Eastern Cooperative Oncology Group; EFS, event-free survival; HiDAC, high-dose cytarabine; MRD, measurable residual disease; OS, overall survival; PS, performance status; RFS, relapse-free survival; RT, radiotherapy; WBC, white blood cell.

Additional information

Funding

This paper was not funded.