Key detail missing in FDA approval of new acute myeloid leukemia drug: How much longer do people live?


4 Star


FDA approves new combination treatment for acute myeloid leukemia

Our Review Summary

acute myeloid leukemia (AML)

This release from the Food and Drug Administration announces approval of a new drug, Rydapt (midostaurin), for the treatment of specific acute myeloid leukemia patients who possess certain genetic FLT3 mutations that affect the immune system. It points out that when these patients are identified through the use of a specific test — the LeukoStrat CDx FLT3 Mutation Assay — then the new drug can be used along with standard chemotherapy until remission and then as a maintenance drug following that.

The descriptions surrounding the benefits of the drug and the evidence are vague. It would have been good to see both absolute and relative benefits included in the release, and a clarification that only about one-third of AML patients will be candidates for this drug treatment.

While there is no mention of the cost of the drug or the test (which FDA releases seldom include), the release provides clear information on harms and how the drug works.


Why This Matters

Acute myeloid leukemia (AML) is a serious and often fatal form of blood cancer, and treatments against it have been limited in the past. AML involves the cells that fight infection in the body.  Increased understanding of the genetics of this disease has identified a large number of genetic mutations associated with the development of AML. This study examines patients with one type of mutation, FLT3. Though not stated in the release, it is estimated that around 30% of patients with AML will have this mutation. While this represents a sizable number of individuals, it is important to acknowledge that most patients diagnosed with AML will not have this mutation and therefore won’t be treated with midostaurin.

As the release points out, “the National Cancer Institute estimated that approximately 19,930 people would be diagnosed with AML in 2016 and 10,430 were projected to die of the disease.”  The situation is worse for those AML patients who possess the FLT3 mutations so this new approach might give both physicians and patients a new alternative treatment.


Does the news release adequately discuss the costs of the intervention?

Not Applicable

There is no mention of the cost of this new drug, Rydapt (midostaurin), or of the cost of the diagnostic tool, the LeukoStrat CDx FLT3 Mutation Assay, which the FDA approved for use in determining the appropriateness of using this drug. Many patients will need to be tested for this mutation in order to find the individuals who have it and thus may benefit from this new drug.

However, the FDA evaluates drugs without considering costs, which is why they are not discussed in this news release. We rate this one Not Applicable.

Does the news release adequately quantify the benefits of the treatment/test/product/procedure?

Not Satisfactory

Although the release does provide some numerical context, it’s insufficient to give credit here. The release could have provided much more useful information about the quantitative benefits. For example, a summary of the trial upon which the approval was based stated,

“At a median follow-up of 57 months, midostaurin reduced mortality risk by 23% compared with placebo plus chemotherapy. The median OS was 74.7 months for the group receiving midostaurin versus 26 months for the placebo group (P = .007), representing a 23% reduction in the risk for death favoring midostaurin.” The release should have provided both absolute as well as relative benefits, both of which were available from the trials.

What the release does say is that patients who received a combination of standard chemotherapy and Rydapt for treating AML “lived longer than patients who received chemotherapy alone, although a specific median survival rate could not be reliably estimated,” compared to patients receiving chemotherapy plus a placebo.  That’s pretty vague. In addition, it said that “patients who received Rydapt in combination with chemotherapy in the trial went longer (median 8.2 months) without certain complications (failure to achieve complete remission within 60 days of starting treatment, progression of leukemia or death) than patients who received chemotherapy alone (median three months).”

Does the news release adequately explain/quantify the harms of the intervention?


The release effectively reports possible side effects experienced by AML patients receiving Rydapt, including “low levels of white blood cells with fever (febrile neutropenia), nausea, inflammation of the mucous membranes (mucositis), vomiting, headache, spots on the skin due to bleeding (petechiae), musculoskeletal pain, nosebleeds (epistaxis), device-related infection, high blood sugar (hyperglycemia) and upper respiratory tract infection.”  It also warns women who are pregnant or breastfeeding to avoid taking Rydapt.  It also points out that the FDA approved the use of Rydapt for other patients with “certain types of rare blood disorders” and provides a list of possible side effects they might experience.

Does the news release seem to grasp the quality of the evidence?

Not Satisfactory

The release explains that the approval follows the completion of a “randomized trial of 717 patients who had not been treated previously for AML.”  It would have been better if the release would have added how many patients were screened with the diagnostic test to identify the 717 patients studied.

While it appears this treatment prolongs survival, it isn’t clear from the release what the time frame is, meaning people may live longer but still may die in the end of the disease.

And while the release states that there are almost 20,000 patients diagnosed with AML each year in the US, it doesn’t state how many may have this mutation and thus be potentially treated with this new therapy. According to a review article published last year, “Approximately 30% of patients with AML carry the FLT3 mutation, which is associated with aggressive disease, with poor prognosis and a high risk for relapse.” That means that most patients with AML will not be eligible for this treatment but the release could give the general public the impression that it will help most patients with AML.

Does the news release commit disease-mongering?


There is no evidence of disease mongering here. AML is a life-threatening condition and new agents that can prolong life are clearly needed. There’s plenty of context about the disease and how the drug works: “Rydapt is a kinase inhibitor that works by blocking several enzymes that promote cell growth. If the FLT3 mutation is detected in blood or bone marrow samples using the LeukoStrat CDx FLT3 Mutation Assay, the patient may be eligible for treatment with Rydapt in combination with chemotherapy.”

Does the news release identify funding sources & disclose conflicts of interest?

Not Satisfactory

The release doesn’t mention who funded the research leading to the approval, although some readers might be able to guess that Novartis Pharmaceuticals, the manufacturer of Rydapt, and Invivoscribe Technologies, the makers of the LeukoStrat CDx FLT3 Mutation Assay, sponsored the trials since the approval was given to them.

Does the news release compare the new approach with existing alternatives?


The new medication was used in combination with standard chemotherapy. That tells us the alternative was standard chemotherapy alone, an important comparison.

Does the news release establish the availability of the treatment/test/product/procedure?


While the release doesn’t specifically state the availability of the drug, the FDA approval for its use suggests that it should start to become available in a matter of months and not years.

Does the news release establish the true novelty of the approach?


The release makes clear that the use of this drug for AML patients with the FLT3 mutation is a new approach for a situation where previous therapies have been marginally successful.

It also claims that the drug is “the first targeted therapy to treat patients with AML, in combination with chemotherapy,” according to an FDA official.

Total Score: 6 of 9 Satisfactory


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