In an interview with Pharmacy Times®, Amir Ali, PharmD, BCOP, clinical pharmacist specialist at the University of Southern California, explains highlights from multiple abstracts he worked on that are set to be presented at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego, California. One abstract focuses on the efficacy of shorter durations of venetoclax (Venclexta; AbbVie, Genentech) in patients with acute myeloid leukemia (AML), while another analyzed the response in patients with B-cell acute lymphocytic leukemia (B-ALL) receiving blinatumomab prior to allogenic hematopoietic stem cell transplant (HSCT).
Ali explains how the results of these trials impact the management and treatment of patients with these hematologic malignancies, and highlights key takeaways for pharmacists and treatment providers.
Pharmacy Times: What are the clinical implications of shorter duration venetoclax regimens in treating newly diagnosed AML patients?
Key Takeaways
1. Shorter Venetoclax Regimens: Shorter durations of venetoclax therapy (e.g., 21, 14, or 7 days) can be equally effective as the standard 28-day regimen in treating newly diagnosed AML patients, while reducing side effects and hospital stays.
2. Blinatumomab's Impact on ALL: Blinatumomab, a bispecific antibody, shows promise in improving outcomes for ALL patients, especially in the Hispanic population. Using blinatumomab before bone marrow transplant can lead to better overall survival.
3. Pharmacist's Role in Hematological Malignancies: Pharmacists play a crucial role in the treatment and management of patients with hematological malignancies. Their involvement in areas like treatment duration optimization, managing side effects, and incorporating new therapies like blinatumomab is becoming increasingly important.
Amir Ali: AML is known to be a fairly dismal disease. When you look at overall survival (OS), 5 years for these patients, you'll see around 15-to-30% survival for these patients. Unfortunately, we haven't had many advances of new therapeutics out there. One of our long-standing available options for care for these patients includes a hypomethylating agent. Examples of that include decitabine or azacytidine, in combination with venetoclax, which is a BCL2 inhibitor. We combine these therapies, often used for patients that are elderly or frail and in different fashions. Part of the way that we use this therapy is we use different durations of our venetoclax therapy. One of the focuses on this study was assessing the length of therapy of using venetoclax as part of these this regimen.
Pharmacy Times: How do the results of this study align with current treatment guidelines for AML, and what impact might they have on future treatment recommendations?
Ali: When you look at the package insert of venetoclax, it recommends the duration of therapy be 28 days. Now, there are a plethora of studies looking at lower durations of therapy: 21 days, 14 days, and even 7 days of therapy. All these studies show that you probably don't need the full 28 days. When you look at shortened duration of therapy, patients are often hospitalized for a lower amount of time, you see patients facing fewer financial toxicities, less neutropenia risk with time. What the results of our study included, which was an n of 85 patients, found that lower treatment duration did not necessarily impact the efficacy of the agent long-term. You saw differences in remission and MRD negativity short-term, but when you look at long-term data, we essentially found no difference in OS for these patients. It lends us the opportunity to potentially use a lower duration of therapy.
Pharmacy Times: How do you envision future studies building upon these findings to further optimize treatment for AML patients?
Ali: I'm hoping this study leads us to some uniformity in practice. We know that many institutions vary in their practice and their treatment durations of HMA- and venetoclax-based regimens. The hope is to create a standardized approach, criterions of lengths of therapies for these patients. I'm hoping that this study will help us in that direction.
Pharmacy Times: Given the promising results of pre-transplant blinatumomab in reducing relapse and improving disease-free survival, what are the next steps in clinical research to further validate its efficacy and safety profile in this patient population?
Ali: Blinatumomab is a form of a bispecific antibody that specifically targets CD19 and CD3 to treat ALL. We know a specific population that is heavily impacted in ALL is the Hispanic population, and one of the fastest growing populations in the United States. Our study specifically looked at the impact of blinatumomab in the treatment of Hispanic patients that have received a bone marrow transplant that included the use of blinatumomab prior to the transplantation. There is a lot of data, including newly approved data, that uses blinatumomab prior to transplantation. There's a study that was approved recently, FDA approved, the E1910 study, that allows us to now incorporate blinatumomab as part of our consolidation regimens in the treatment of ALL patients. What our study specifically found, is when you're incorporating blinatumomab prior to bone marrow transplant, these patients do better across the board, regardless of their baseline cytogenetics, regardless of their other comorbidities that they have. This really reinforces the use of blinatumomab as part of our ALL regimen, regardless of the patient, including the Hispanic patient population.
Pharmacy Times: How do you see the integration of blinatumomab into standard-of-care treatment regimens for adult B-ALL patients undergoing allogeneic HSCT, particularly considering the potential for increased costs and complex treatment schedules?
The 66th ASH Annual Meeting and Exposition takes place from Saturday, December 7 to Tuesday, December 10 in San Diego, California. You can follow our continuing coverage here.
Ali: Absolutely. Blinatumomab has historically been approved for patients with relapsed and refractory ALL, including patients who are MRD positive. But there has been a transition in our use of blinatumomab, including the ability to use blinatumomab for patients in the frontline setting, using it in the consolidation regimen. With that new approval and that increase in available options for these patients, comes certain challenges, mainly prolonging the duration of these therapies. When you're adding a new treatment option, including that into your regimen, the length can increase. Blinatumomab also comes with its unique side effect profile, including the risks of cytokine release syndrome and neurotoxicity. Oftentimes, these patients must be admitted in the hospital when you're first starting for observation. Lastly, the financial toxicity these patients should be always included and considered as well when we're using blinatumomab in our treatment regimens.
Pharmacy Times: Is there anything else you would like to add?
Ali: With these updates of therapy, we are truly starting to see the valuable impact that pharmacists have in the treatments of patients with any hematological malignancy. We're seeing more pharmacists involved with these patients, more oncology pharmacists attending ASH than they have ever before. We've just shared a few examples of how pharmacists can play a key role in the treatment and management of patients with hematological malignancies, namely, the duration of therapy on venetoclax, incorporating blinatumomab, and the management of side effects of blinatumomab, and the treatment of our patients with AML. I think our involvement and the power of the pharmacist is continuing to grow each year, and our providers, our institutions are seeing the value of their role as well.
