Phase Ib trial of lenalidomide as post-remission therapy for older adults with acute myeloid leukemia: Safety and longitudinal assessment of geriatric functional domains

2021 ◽  
Author(s):  
Justin D. Woods ◽  
Joshua F. Zeidner ◽  
Hendrik W. Van Deventer ◽  
Katarzyna Jamieson ◽  
Melissa Matson ◽  
...  
Keyword(s):  
Older Adults ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Functional Domains ◽  
Longitudinal Assessment ◽  
Phase Ib ◽  
Acute Myeloid

scholarly journals Venetoclax Combined With Low-Dose Cytarabine for Previously Untreated Patients With Acute Myeloid Leukemia: Results From a Phase Ib/II Study

2019 ◽  
Vol 37 (15) ◽  
pp. 1277-1284 ◽  
Author(s):  
Andrew H. Wei ◽  
Stephen A. Strickland ◽  
Jing-Zhou Hou ◽  
Walter Fiedler ◽  
Tara L. Lin ◽  
...  
Keyword(s):  
Older Adults ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Blood Count ◽  
Low Dose ◽  
Intensive Chemotherapy ◽  
Phase Ib ◽  
Low Dose Cytarabine ◽  
Acute Myeloid ◽  
Count Recovery

PURPOSE Effective treatment options are limited for patients with acute myeloid leukemia (AML) who cannot tolerate intensive chemotherapy. An international phase Ib/II study evaluated the safety and preliminary efficacy of venetoclax, a selective B-cell leukemia/lymphoma-2 inhibitor, together with low-dose cytarabine (LDAC) in older adults with AML. PATIENTS AND METHODS Adults 60 years or older with previously untreated AML ineligible for intensive chemotherapy were enrolled. Prior treatment of myelodysplastic syndrome, including hypomethylating agents (HMA), was permitted. Eighty-two patients were treated at the recommended phase II dose: venetoclax 600 mg per day orally in 28-day cycles, with LDAC (20 mg/m2 per day) administered subcutaneously on days 1 to 10. Key end points were tolerability, safety, response rates, duration of response (DOR), and overall survival (OS). RESULTS Median age was 74 years (range, 63 to 90 years), 49% had secondary AML, 29% had prior HMA treatment, and 32% had poor-risk cytogenetic features. Common grade 3 or greater adverse events were febrile neutropenia (42%), thrombocytopenia (38%), and WBC count decreased (34%). Early (30-day) mortality was 6%. Fifty-four percent achieved complete remission (CR)/CR with incomplete blood count recovery (median time to first response, 1.4 months). The median OS was 10.1 months (95% CI, 5.7 to 14.2), and median DOR was 8.1 months (95% CI, 5.3 to 14.9 months). Among patients without prior HMA exposure, CR/CR with incomplete blood count recovery was achieved in 62%, median DOR was 14.8 months (95% CI, 5.5 months to not reached), and median OS was 13.5 months (95% CI, 7.0 to 18.4 months). CONCLUSION Venetoclax plus LDAC has a manageable safety profile, producing rapid and durable remissions in older adults with AML ineligible for intensive chemotherapy. High remission rate and low early mortality combined with rapid and durable remission make venetoclax and LDAC an attractive and novel treatment for older adults not suitable for intensive chemotherapy.

New Strategies for the Treatment of Acute Myeloid Leukemia Including Antibodies and Other Novel Agents

Hematology ◽  
2005 ◽  
Vol 2005 (1) ◽  
pp. 143-150 ◽  
Author(s):  
Martin S. Tallman
Keyword(s):  
Older Adults ◽  
Acute Myeloid Leukemia ◽  
Multidrug Resistance ◽  
Myeloid Leukemia ◽  
Cytotoxic Agents ◽  
High Dose ◽  
Farnesyltransferase Inhibitors ◽  
Younger Adults ◽  
The Impact ◽  
Acute Myeloid

Abstract The prognosis for younger adults (≤ 55–60 years) with acute myeloid leukemia (AML) has improved during the last four decades. However, there has been little progress in the treatment of older adults. This disappointing observation is important because the median age of patients with AML is about 70 years. Approximately 60%–80% of younger adults with AML achieve complete remission (CR) with the cytotoxic agents cytarabine and an anthracycline such as daunorubicin or idarubicin or the anthracenedione mitoxantrone. However, only 30%–40% of such patients are alive and disease-free at 5 years. Among older adults, CR is achieved in 40%–55%, but there are very few long-term survivors. Many studies have evaluated the impact of alternative doses and schedules, as well as additional cytotoxic drugs, on the prognosis for this group of patients. The outcome has not improved substantially beyond that achieved with conventional doses of an anthracycline and cytarabine followed by high-dose cytarabine consolidation. Several factors identified at diagnosis can predict outcome. The most important of these is the karyotype of the leukemic cells. Another critical factor is the presence of transmembrane transporter proteins, which confer multidrug resistance and mutations in or overexpression of specific genes such as WT1, C/EBPα, BAX, and BCL-2/BAX ratio, BAALC, EVI1, KIT and FLT3. The development of specific agents directed at gene mutations, signal transduction pathways and unique cell surface antigens provide the foundation for new therapeutic strategies. Such agents include the immunoconjugate gemtuzumab ozogamicin, multidrug resistance inhibitors, farnesyltransferase inhibitors, histone deacetylase and proteosome inhibitors, antiangiogenesis agents, FLT3 inhibitors, apoptosis inhibitors, and nucleoside analogs. All of these agents can potentially address the heterogeneous abnormalities in AML and significantly improve the outcome for patients.

scholarly journals Decitabine as a First-Line Treatment for Older Adults Newly Diagnosed with Acute Myeloid Leukemia

2017 ◽  
Vol 58 (1) ◽  
pp. 35 ◽  
Author(s):  
Hyunsung Park ◽  
Haerim Chung ◽  
Jungyeon Lee ◽  
Jieun Jang ◽  
Yundeok Kim ◽  
...  
Keyword(s):  
Older Adults ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Line Treatment ◽  
Newly Diagnosed ◽  
First Line ◽  
First Line Treatment ◽  
Acute Myeloid

scholarly journals Whom should we treat with novel agents? Specific indications for specific and challenging populations

Hematology ◽  
2021 ◽  
Vol 2021 (1) ◽  
pp. 24-29
Author(s):  
Lindsay Wilde ◽  
Margaret Kasner
Keyword(s):  
Older Adults ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
New Therapies ◽  
Novel Treatments ◽  
Relapsed Disease ◽  
Disease Understanding ◽  
Rapid Shift ◽  
Special Patient ◽  
Acute Myeloid

Abstract A relative wealth of new therapies for acute myeloid leukemia (AML) have led to a rapid shift in treatment paradigms for this disease. Understanding whom, when, and how to treat is more complex than ever before. Here we explore whom to treat with these available new therapies, focusing on special patient populations that include older adults, those with relapsed disease, and those with TP53-mutated AML. These high-risk subgroups are some of the most challenging to care for, but novel treatments are providing them with new hope.

scholarly journals A Phase Ib Study of Onvansertib, a Novel Oral PLK1 Inhibitor, in Combination Therapy for Patients with Relapsed or Refractory Acute Myeloid Leukemia

2020 ◽  
Vol 26 (23) ◽  
pp. 6132-6140
Author(s):  
Amer M. Zeidan ◽  
Maya Ridinger ◽  
Tara L. Lin ◽  
Pamela S. Becker ◽  
Gary J. Schiller ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Combination Therapy ◽  
Myeloid Leukemia ◽  
Phase Ib ◽  
Refractory Acute Myeloid Leukemia ◽  
Acute Myeloid
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