Venetoclax + Decitabine Improve Senior AML Patients’ Chances of Receiving a Transplant

When preparing acute myeloid leukemia (AML) patients for a stem cell transplant, is there a better option than intensive chemotherapy? 

Insights from an Italian study reveal that the combination of venetoclax and decitabine is more effective than standard intensive chemotherapy when preparing those with AML for an allogeneic stem cell transplant. Learn how this treatment combination helped a higher percentage of patients achieve a complete reduction in AML signs/symptoms and reach the transplant stage. 

What are Venetoclax + Decitabine for AML?  

The treatment combination of venetoclax (Venclexta, AbbVie) and decitabine (Dacogen, Astex) is approved by the FDA as an initial treatment for people with acute myeloid leukemia (AML) who are older or not suitable for intensive chemotherapy. However, it is not yet approved as a preparatory treatment for an allogeneic stem cell transplant (allo-SCT), which typically requires intensive chemotherapy as the standard pre-treatment. 

Venetoclax combined with decitabine has been effective in helping 60-70% of senior AML patients achieve complete remission, meaning a full reduction in cancer signs and symptoms. This raises the question: Could this combination serve as an alternative to intensive chemotherapy to prepare patients for an allo-SCT? Using venetoclax and decitabine might help patients avoid the harsh side effects of intensive chemotherapy and increase their likelihood of successfully reaching an allo-SCT. 

Currently, about 50% of senior AML patients achieve complete remission from traditional intensive chemotherapy that includes anthracycline, and only 15% of patients who are treated can receive an allo-SCT. This low rate is due to treatment-related side effects, worsening of other health conditions, or delays in being referred to a transplant center. 

How Effective are Venetoclax + Decitabine as a Treatment Before Allogeneic Stem Cell Transplant? 

To explore this question further, Professor Domenico Russo, PhD from the University of Brescia in Italy, initiated research to assess whether venetoclax and decitabine could be a more effective first treatment for senior AML patients aiming for an allo-SCT. 

Who were the patients in the study? 

Professor Russo's research centered on 93 senior AML patients. Of these, 47% had intermediate-risk AML, while 53% had high-risk AML. 

How venetoclax + decitabine were administered in the study 

The patients received venetoclax taken by mouth daily for about two months (also called cycles). Decitabine was given intravenously (IV) from days one to five of each cycle. At first, patients were hospitalized for at least 24 hours, but following treatments were given on an outpatient basis. This means that patients did not need to remain in the hospital overnight to receive treatment.  

After two cycles, the doctors checked to see if the patients’ AML signs and symptoms were decreasing via minimal residual disease (MRD) testing. If patients had a full reduction in AML signs/symptoms (referred to as a complete response), they were scheduled for an allo-SCT, ideally within two months.

Additional treatment cycles with venetoclax and decitabine were given if the patients had not yet achieved complete remission. Treatment was only discontinued if the person experienced severe side effects, was non-compliant with study rules, or decided to withdraw from the study. The most common side effects from treatment were infections and low blood counts. 

Percentage of patients who achieved complete remission and made it to transplant  

74% of patients achieved complete remission after two treatment cycles. Even more encouraging is that 57% of all patients treated and 83% of those who reached complete remission were able to proceed to allo-SCT. 

This is a significant improvement over previous studies, which reported that only about 15% of older AML patients proceeded to allo-SCT after intensive chemotherapy pre-treatment. 

Low relapse rates despite transplant scheduling delays 

After finishing the two-month treatment, it took most patients more time than the planned two-month waiting period following treatment to receive their stem cell transplant. 

This was due to logistical delays like scheduling conflicts and finding a donor match. Despite the added time to get to their transplant, the majority of patients did not relapse before the allo-SCT—only 8% of patients who had achieved remission relapsed before receiving their transplant. 

Key Takeaways

In summary, venetoclax and decitabine are effective for the majority of senior AML patients eligible for an allogeneic stem cell transplant. Most patients achieve complete remission with this treatment and stay healthy enough to proceed with the transplant. The study also found that it is safe to administer this treatment in an outpatient setting, which removes the necessity for prolonged hospital stays. 

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Sources: 

• Venetoclax plus decitabine as a bridge to allogeneic haematopoietic stem-cell transplantation in older patients with acute myeloid leukaemia (VEN-DEC GITMO): final report of a multicentre, single-arm, phase 2 trial

• Transplantation and long-term overall survival in acute myeloid leukaemia  

• Venclexta