Leukemia treatment has taken a significant step forward as the National Institute for Health and Care Excellence (NICE) has issued evidence-based recommendations for the use of ivosidenib (Tibsovo) in combination with azacitidine for treating untreated acute myeloid leukemia (AML) with an IDH1 R132 mutation in adults who cannot undergo standard intensive induction chemotherapy. This combination therapy is recommended within its marketing authorization and is only suggested if provided under the company’s commercial arrangement.
The standard treatment for newly diagnosed AML with an IDH1 R132 mutation in adults who cannot undergo standard intensive induction chemotherapy is venetoclax plus azacitidine. Although ivosidenib plus azacitidine has not been directly compared with venetoclax plus azacitidine in clinical trials, an indirect comparison suggests that ivosidenib plus azacitidine may increase both overall survival and the time before the condition worsens compared to venetoclax plus azacitidine.
The most likely cost-effectiveness estimates for ivosidenib plus azacitidine fall within the range that NICE considers acceptable for NHS resource utilization. Consequently, this combination therapy is recommended. Ivosidenib, in combination with azacitidine, is indicated for treating adult patients with newly diagnosed acute myeloid leukemia with an IDH1 R132 mutation who are ineligible for standard induction chemotherapy. Ivosidenib is available to the NHS at a discounted price under a commercial arrangement.
New Hope for Acute Myeloid Leukemia Patients with Ivosidenib-Azacitidine Therapy
A patient expert highlighted that existing treatments for AML mainly involve chemotherapy and stem cell transplants, which are not suitable for all patients. Intensive induction chemotherapy is particularly challenging, both physically and psychologically, even for physically fit individuals. Before the approval of venetoclax plus azacitidine, survival rates for AML were poor for those unable to undergo intensive induction chemotherapy.
The clinical expert emphasized the need for alternative treatments, noting that ivosidenib plus azacitidine could be a preferable option due to lower hematological toxicity compared to venetoclax plus azacitidine. Approximately 6% to 10% of acute myeloid leukemia patients have an IDH1 R132 mutation and would benefit from this new treatment option. Ivosidenib, being an oral treatment, is preferable to intravenous treatments for many patients.
The primary treatment for AML involves intensive induction chemotherapy to induce remission, followed by consolidation chemotherapy, maintenance therapy, and potentially a stem cell transplant. However, more than 50% of acute myeloid leukemia patients cannot undergo intensive induction chemotherapy or stem cell transplants due to age or comorbidities. Standard care for these patients has been venetoclax plus azacitidine. Other treatment options include low-dose cytarabine, azacitidine (for AML with 20% to 30% bone marrow blasts), and venetoclax plus low-dose cytarabine (for acute myeloid leukemia with more than 30% bone marrow blasts).
NICE Recommends Ivosidenib-Azacitidine for Acute Myeloid Leukemia
Venetoclax plus azacitidine is considered the most relevant comparator for ivosidenib plus azacitidine. Although other treatments are available, they are typically considered in exceptional cases due to poorer outcomes. The AGILE trial provided direct comparative clinical-effectiveness evidence for ivosidenib plus azacitidine, showing significant improvements in event-free and overall survival compared to azacitidine plus placebo. Due to the lack of direct comparative evidence, an indirect comparison using network meta-analysis (NMA) was conducted, suggesting that ivosidenib plus azacitidine may improve survival outcomes compared to venetoclax plus azacitidine. However, there were uncertainties due to the small sample size and heterogeneity across studies.
The company submitted a partitioned survival model with Markov components, using endpoints from the AGILE trial to inform health states. The model assumptions included a cure assumption at 3 years with a standardized mortality ratio (SMR) of 1.2, and a Weibull distribution for long-term survival estimates. The cost-effectiveness estimates resulted in a deterministic incremental cost-effectiveness ratio (ICER) under £30,000 per quality-adjusted life year (QALY) gained, which is considered acceptable by NICE. Ivosidenib plus azacitidine was recognized as an innovative treatment, offering the first targeted therapy for acute myeloid leukemia with an IDH1 mutation.
The committee concluded that ivosidenib plus azacitidine is a cost-effective use of NHS resources and recommended it for routine use in the NHS for treating newly diagnosed AML with an IDH1 R132 mutation in adults who cannot have standard intensive induction chemotherapy. This recommendation will be implemented within three months of publication, ensuring that patients have timely access to this new treatment option.
Resource: The National Institute for Health and Care Excellence , June 05, 2024
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