Faculty Opinions recommendation of High-dose daunorubicin in older patients with acute myeloid leukemia.

Abstract Older patients with acute myeloid leukemia (AML) have limited treatment options and a poor prognosis, thereby warranting novel therapeutic strategies. We evaluated the efficacy of lenalidomide as front-line therapy for older AML patients. In this phase 2 study, patients 60 years of age or older with untreated AML received high-dose (HD) lenalidomide at 50 mg daily for up to 2 28-day cycles. If patients achieved a complete remission (CR)/CR with incomplete blood count recovery (CRi) or did not progress after 2 cycles of HD lenalidomide, they received low-dose lenalidomide (10 mg daily) until disease progression, an unacceptable adverse event, or completion of 12 cycles. Thirty-three AML patients (median age, 71 years) were enrolled with intermediate (55%), unfavorable (39%), or unknown (6%) cytogenetic risk. Overall CR/CRi rate was 30%, and 53% in patients completing HD lenalidomide. The CR/CRi rate was significantly higher in patients presenting with a low (< 1000/μL) circulating blast count (50%, P = .01). The median time to CR/CRi was 30 days, and duration of CR/CRi was 10 months (range, 1- ≥ 17 months). The most common grades ≥ 3 toxicities were thrombocytopenia, anemia, infection, and neutropenia. HD lenalidomide has evidence of clinical activity as initial therapy for older AML patients, and further study of lenalidomide in AML and MDS is warranted. This study is registered at www.clinicaltrials.gov as #NCT00546897.

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Current Therapeutic Results and Treatment Options for Older Patients with Relapsed Acute Myeloid Leukemia

Cancers ◽

10.3390/cancers11020224 ◽

2019 ◽

Vol 11 (2) ◽

pp. 224 ◽

Cited By ~ 14

Author(s):

Felicetto Ferrara ◽

Federica Lessi ◽

Orsola Vitagliano ◽

Erika Birkenghi ◽

Giuseppe Rossi

Keyword(s):

Acute Myeloid Leukemia ◽

Older Patients ◽

Myeloid Leukemia ◽

Randomized Clinical Trials ◽

Clinical Decision Making ◽

New Drugs ◽

Clinical Activity ◽

High Dose ◽

Therapeutic Results ◽

Acute Myeloid

Considerable progress has been made in the treatment of acute myeloid leukemia (AML). However, current therapeutic results are still unsatisfactory in untreated high-risk patients and poorer in those with primary refractory or relapsed disease. In older patients, reluctance by clinicians to treat unfit patients, higher AML cell resistance related to more frequent adverse karyotype and/or precedent myelodysplastic syndrome, and preferential involvement of chemorefractory early hemopoietic precursors in the pathogenesis of the disease further account for poor prognosis, with median survival lower than six months. A general agreement exists concerning the administration of aggressive salvage therapy in young adults followed by allogeneic stem cell transplantation; on the contrary, different therapeutic approaches varying in intensity, from conventional salvage chemotherapy based on intermediate–high-dose cytarabine to best supportive care, are currently considered in the relapsed, older AML patient population. Either patients’ characteristics or physicians’ attitudes count toward the process of clinical decision making. In addition, several new drugs with clinical activity described as “promising” in uncontrolled single-arm studies failed to improve long-term outcomes when tested in larger randomized clinical trials. Recently, new agents have been approved and are expected to consistently improve the clinical outcome for selected genomic subgroups, and research is in progress in other molecular settings. While relapsed AML remains a tremendous challenge to both patients and clinicians, knowledge of the molecular pathogenesis of the disease is fast in progress, potentially leading to personalized therapy in most patients.

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A phase 2 study of high-dose lenalidomide as initial therapy for older patients with acute myeloid leukemia

Yearbook of Oncology ◽

10.1016/j.yonc.2011.08.036 ◽

2011 ◽

Vol 2011 ◽

pp. 125-126

Author(s):

R.J. Arceci

Keyword(s):

Acute Myeloid Leukemia ◽

Older Patients ◽

Myeloid Leukemia ◽

Initial Therapy ◽

High Dose ◽

Phase 2 ◽

Phase 2 Study ◽

Acute Myeloid

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Midostaurin added to chemotherapy and continued single-agent maintenance therapy in acute myeloid leukemia with FLT3-ITD

Blood ◽

10.1182/blood-2018-08-869453 ◽

2019 ◽

Vol 133 (8) ◽

pp. 840-851 ◽

Cited By ~ 69

Author(s):

Richard F. Schlenk ◽

Daniela Weber ◽

Walter Fiedler ◽

Helmut R. Salih ◽

Gerald Wulf ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Maintenance Therapy ◽

Older Patients ◽

Myeloid Leukemia ◽

Hematopoietic Cell Transplantation ◽

Kinase Inhibitor ◽

Single Agent ◽

High Dose ◽

Historical Controls ◽

Acute Myeloid

Abstract Patients with acute myeloid leukemia (AML) and a FLT3 internal tandem duplication (ITD) have poor outcomes to current treatment. A phase 2 hypothesis-generating trial was conducted to determine whether the addition of the multitargeted kinase inhibitor midostaurin to intensive chemotherapy followed by allogeneic hematopoietic cell transplantation (alloHCT) and single-agent maintenance therapy of 12 months is feasible and favorably influences event-free survival (EFS) compared with historical controls. Patients 18 to 70 years of age with newly diagnosed AML and centrally confirmed FLT3-ITD were eligible: 284 patients were treated, including 198 younger (18-60 years) and 86 older (61-70 years) patients. Complete remission (CR) rate, including CR with incomplete hematological recovery (CRi) after induction therapy, was 76.4% (younger, 75.8%; older, 77.9%). The majority of patients in CR/CRi proceeded to alloHCT (72.4%). Maintenance therapy was started in 97 patients (34%): 75 after alloHCT and 22 after consolidation with high-dose cytarabine (HiDAC). Median time receiving maintenance therapy was 9 months after alloHCT and 10.5 months after HiDAC; premature termination was mainly a result of nonrelapse causes (gastrointestinal toxicity and infections). EFS and overall survival at 2 years were 39% (95% confidence interval [CI], 33%-47%) and 34% (95% CI, 24%-47%) and 53% (95% CI, 46%-61%) and 46% (95% CI, 35%-59%) in younger and older patients, respectively. EFS was evaluated in comparison with 415 historical controls treated within 5 prospective trials. Propensity score-weighted analysis revealed a significant improvement of EFS by midostaurin (hazard ratio [HR], 0.58; 95% CI, 0.48-0.70; P < .001) overall and in older patients (HR, 0.42; 95% CI, 0.29-0.61). The study was registered at www.clinicaltrials.gov as #NCT01477606.

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