June 30, 2022

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New progress in the treatment of acute myeloid leukemia

New progress in the treatment of acute myeloid leukemia



 

New progress in the treatment of acute myeloid leukemia.

Acute myeloid leukemia is the most common type of leukemia, mostly in people over 65 years of age.

 

Acute myeloid leukemia (AML) is one of the most common leukemias. It mostly occurs in middle-aged and elderly people over 65.

The disease progresses rapidly. It is one of the most aggressive and difficult to treat blood cancers.

If they are not treated in time, they usually die within a few weeks or months, and the survival rate is extremely low.

 

AML can be divided into many types. Different cases have different chromosomal changes, gene mutations and epigenetic modifications.

It is difficult to find new therapies that are suitable for most patients.

Although great progress has been made in the treatment of AML in recent years, the five-year survival rate is still less than 30%.

 

Now, Good Doctor will show you what new developments are in the AML field?

 

 

 

▌Oral maintenance therapy with azacitidine significantly improves survival rate

 New progress in the treatment of acute myeloid leukemia 

 

A few days ago, a research team from Monash University in Australia reported that after the first remission of elderly patients with acute myeloid leukemia (AML), oral azacitidine maintenance therapy can improve the 10-month survival rate.

 

In September last year, the therapy was approved by the FDA. This approval is based on a phase III controlled trial QUAZAR AML-001.

 

The trial enrolled 472 patients with AML over 55 years old (first remission after standard induction therapy and not eligible for stem cell transplantation).

The median OS of patients in the azacitidine maintenance group was 24.7 months, compared with 14.8 months in the placebo group.

 

 

 

 

▌Combination therapy improves survival rate

A study (VIALE-A) reported by the research team of MD Anderson Cancer Center at the Virtual Annual Meeting of the European Society of Hematology showed:

In 431 new-onset AML patients (median age 76 years, randomized at a ratio of 2:1), the combination of Bcl-2 inhibitor Venetoclax and standard AML therapy can significantly improve overall survival (OS), median OS was extended from 9.6 months in the standard azacitidine group to 14.7 months in the combined treatment group.

The complete remission rates were 28.3% and 66.4%, and the median remission time was 13.4 months and 17.5 months, respectively; and no need The blood transfusion rate is significantly improved.

Among them, 35% and 60% of patients do not need red blood cell transfusion, 50% and 69% of patients do not need platelet transfusion, and 34% and 58% of patients do not require transfusion of both blood components. 

 

New progress in the treatment of acute myeloid leukemia

 

 

Moreover, the combination therapy has a rapid remission, usually within one cycle, and can be seen in all cytogenetic risk groups and molecular mutation subgroups.

 

In addition, “Nature Communications” recently published a study jointly conducted by the Sanford Burnham Prebys Institute of Medicine and the University of Glasgow, which identified DM2 inhibitors and BET The combination of the two drugs of inhibitor is effective for acute myeloid leukemia (AML) (the effect of the two drugs is not good when treated as a single agent).

This new study provides a scientific basis for advancing the clinical research of combination medication for patients with acute myeloid leukemia.

 

MDM2 inhibitors can activate p53, and BET inhibitors can inhibit leukemia-related genes (BRD4 protein), but not p53. When these two drugs are used in combination, they will produce a synergistic lethal effect and fully release the anti-cancer activity of p53.

 

 

 

▌Liposome drugs are better than standard therapies

A clinical trial involving 309 patients with new-onset high-risk secondary AML (246 patients meet the WHO AML-MRC criteria and were randomly assigned to liposomal cytarabine-daunorubicin (CPX- 351) group or 7+3 regimen group (2020 TCTM), the primary end point is complete remission (CR)) The results showed: Compared with the conventional 7+3 regimen induction, CPX-351 treatment of AML and myelodysplasia related changes (AML- The median OS of MRC patients was prolonged by nearly 8 months, 19.15 months and 11.58 months, respectively, and the CR/CRi rates were 48% and 33%, respectively.

 

In patients with CR or CRi, CPX-351 reduced the survival risk by 42%, and the 1-year OS rate (64% vs 43%) and 2-year OS rate (48% vs 31%) were significantly improved. There are similar improvements in abnormal syndrome (MDS) karyotype or previous MDS patients.

 

 

 

▌New guidelines emphasize personalized treatment

The new guidelines of the American Society of Hematology (ASH) recommend that newly diagnosed AML patients who are suitable for anti-leukemia treatment should receive anti-leukemia treatment rather than supportive treatment; for patients where conditions permit, intensive treatment rather than reduced intensity treatment should be used.

 

For patients in end-stage or hospice care, palliative red blood cell infusion should be given, which is beneficial to patients who have not received anti-leukemia treatment.

 

According to the ASH guidelines, no matter what treatment strategy is adopted, clinicians and patients should communicate carefully and carefully before making clinical decisions.

 

For patients in remission, other recommendations support post-remission treatment, rather than no additional treatment; for patients who are not suitable for intensive treatment, demethylation drugs or low-dose cytarabine are recommended; low-intensity treatment is effective and has no side effects Patients can continue treatment.

 

 

 

 

 

▌New antibody drugs are expected to increase transplantation rates

A randomized trial conducted by the research team at Memorial Sloan Kettering Cancer Center showed that the use of radiolabeled anti-CD45 monoclonal antibody 131I apamistamab (Iomab-B) compared to standard regimen treatment can make patients eligible for allogeneic stem cell transplantation (SCT) The number of patients has increased fourfold.

 

New progress in the treatment of acute myeloid leukemia

 

 

The interim analysis of this phase III randomized study SIERRA included patients with relapsed/refractory AML and assigned Iomab-B or standard therapy.

The primary endpoint is persistent CR, defined as CR lasting at least 6 months.

 

The results showed that 37 and 38 patients were enrolled in the Iomab-B group and the standard therapy group, respectively, and 31 and 7 patients received SCT after treatment.

Twenty patients in the standard therapy group who did not meet the requirements for transplantation were crossed over to the Iomab-B group and all received transplantation treatment.

 

Iomab-B treatment followed by SCT, the neutrophil and platelet transplantation rate was 100%, and there was no failure. Iomab-B-related non-recurring mortality is low and has good non-hematological toxicity.

 

 

 

 

▌ MRD as the end point or better

The meta-analysis of 80 studies (11,000 cases) included by the MD Anderson Cancer Center research team in the United States showed that MRD negative conversion therapy in AML clinical trials can significantly improve survival (JAMA Oncology).

 

In the MRD-negative group, the risk of disease-free survival was reduced by 63%, and the risk of OS was reduced by 64%.

The 5-year DFS rate in the MRD-negative group is estimated to be 64%, while the MRD-positive group is 25%, and the estimated 5-year OS rate is 68% and 34%, respectively.

 

The relationship between MRD negative and survival can be seen in age, disease subtype, evaluation time, specimen source and most MRD detection methods.

 

Researchers believe that using MRD status as the eligibility criteria and/or the endpoint of clinical trial design is expected to be more effective in evaluating the efficacy of new drugs and combination therapies.

 

 

 

 

New progress in the treatment of acute myeloid leukemia

(source:internet, reference only)


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