According to several publications, the chemotherapy agent Vidaza® (azacitadine) provides an effective treatment alternative for elderly patients diagnosed with acute myeloid leukemia (AML) who cannot tolerate standard intensive therapy. Vidaza has demonstrated promising activity in the treatment of myelodysplastic syndromes and AML.1,2
Acute myeloid leukemia (AML) is a cancer of the bone marrow and blood that is characterized by the rapid, uncontrolled growth of immature white blood cells known as myelocytes. The disease is more common in adults than in children; average age at diagnosis is more than 65 years.
Treatment of AML often begins with induction therapy that includes chemotherapy to produce a complete remission (defined as the disappearance of leukemia cells in the bone marrow and normalization of the white blood cell, red blood cell, and platelet levels). After induction therapy, patients generally receive additional treatment (consolidation therapy) to reduce the likelihood of leukemia recurrence.
There have been relatively large improvements in survival of younger patients with AML over the past few decades due to increased dose-intensity of therapy; this includes stem cell transplants. However, there has been little if any improvement in the treatment of elderly patients with AML, often because elderly patients are not able to tolerate the more aggressive treatments used for younger patients.
Patients with AML unable to undergo stem cell transplant who received maintenance therapy with oral Vidaza experienced longer overall survival and decreased leukemia recurrences, according to research published in The Jan, 2021 New England Journal of Medicine.
The current clinical trial directly compared oral vidaza to placebo in 472 patients with AML in first remission after intensive chemotherapy. All patients were older than age 55 years in complete remission, and were not candidates for hematopoietic stem cell transplantation.
Overall survival duration for patients receiving oral vidaz was significantly longer than those receiving placebo; 24.7 months vs 14.8 months. The median follow-up time was 41.2 months. Relapse-free survival at 1 year was also higher (44.9% vs 27.4% with placebo).
Vidaza Combinations
Currently Vidaza combined with Venclexta is the standard treatment for individuals with AML ineligible for stem cell transplant. Clinical trials are ongoing that are evaluating new drug combinations designed to target specific leukemia causing mutations.
VIALE-A Clinical Trial
VIALE-A compared Venclexta plus Vidaza to Vidaza alone in 431 people with previously untreated acute AML ineligible for intensive chemotherapy. The combination of Venclexta® and Vidaza showed a statistically significant improvement in overall survival.1,2
Vidaza + Revlimid
The sequential combination of Vidaza® and Revlimid® (lenalidomide) shows evidence of clinical activity as initial therapy for older patients with acute myeloid leukemia.3
Vidaza works by targeting aspects of DNA expression, ultimately killing cancer cells. It is used in the treatment of AML and myelodysplastic syndromes (MDS). Revlimid is an oral targeted agent that can stop or slow the growth of cancerous cells within the bone marrow. It is approved in combination with dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. Previous studies have shown that both Vidaza and Revlimid have single-agent activity in patients over age 60 with untreated AML.
Researchers conducted a phase II study of 41 patients age 60 or older (median age 74) with untreated AML. Patients received Vidaza for 7 days followed by escalating doses of Revlimid daily for 21 days on 42-day cycles. Treatment was continued until disease progression, unacceptable adverse event or completion of 12 cycles.
The results indicated that the overall response rate was 41%, with 29% of patients achieving a complete response (CR/CRi). The median time to CR and CRi was 12 weeks and the median duration of response (CR/CRi/PR) was 28 weeks. Median overall survival was 20 weeks for all patients and 69 weeks for patients who responded to therapy. Patients who experienced a response had an improved overall survival compared to non-responders (69 weeks vs. 15 weeks). Baseline characteristics, such as age at diagnosis, baseline white blood cell count, bone marrow blast percentage, were not predictive of responses. Grade 3 or higher adverse events were uncommon. Most adverse events were gastrointestinal, fatigue, and myelosupression.
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Reference:
- Sudan N, Rossetti J, Shadduck R, et al. Treatment of Acute Myelogenous Leukemia with Outpatient Azacitadine. Cancer. Early online publication. September 11, 2006. DOI: 10.1002/cncr.22204.
- Wei AH, Döhner H, Pocock C, et al. Oral azacitidine maintenance therapy for acute myeloid leukemia in first remission. N Engl J Med. 2020;383(26):2526-2537. doi:10.1056/NEJMoa2004444
- Pollyea DA, Zehnder JL, Coutre S, et al. Azacitidine plus lenalidomide for untreated AML patients ineligible for conventional chemotherapy. Blood (ASH Annual Meeting Abstracts) 2012 120: Abstract 3575.
