Potential Need to Update Recommendations for CNS Prophylaxis in ALL

Over the past few decades, research has advanced the therapeutic landscape of acute lymphoblastic leukemia (ALL), especially for adult patients with Philadelphia chromosome (Ph)-positive ALL.¹

With the emergence of tyrosine kinase inhibitors and use of targeted immunotherapies in the front line, outcomes for patients with ALL have significantly improved. However, central nervous system (CNS) management remains important, and questions about CNS involvement and prophylaxis persist.

According to Partow Kebriaei, MD, the standard prophylaxis of CNS disease in ALL is most common with the use of intrathecal chemotherapy. However, with new developments in the field, up-front treatment options for this patient population are changing. This has led experts such as Kebriaei to ask whether recommendations regarding the optimal approach to CNS prophylaxis are the same as they were 2 decades ago. Kebriaei is a professor, Department of Stem Cell Transplantation, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston.

“There has not been, to my knowledge, a recent prospective study looking to see what the optimal extent of prophylaxis should be. Our prophylactic regimens are based on very old studies, mainly in the pediatric space…[and] my talk will be focusing on adults,” Kebriaei told The SOHO Daily News in an interview prior her presentation on 11th Annual Meeting of the Society of Hematologic Oncology (SOHO 2023).

Kebriaei discussed the management of CNS disease and relapse and how more research is needed regarding intrathecal therapy for CNS prophylaxis in adult patients with ALL. The presentation focused on the risk of relapse in the CNS for patients with ALL, specifically adult patients. Kebriaei addressed whether treatments for CNS should be altered, what the optimal approach for CNS prophylaxis is, and whether the same recommendations made a decade ago for CNS prophylaxis should stay the same despite significant changes in the up-front therapy for patients with ALL. “I will review current CNS prophylaxis regimens for adults with ALL,” Kebriaei said.

The management of CNS disease can be a challenge for physicians due to the impermeability of the blood-brain barrier to many systemic therapies.² Emerging therapies are now attempting to minimize toxicity and focus efforts on improving quality of life.3 Although there are published guidelines on mainly intrathecal therapy for CNS prophylaxis in adult patients with ALL, Kebriaei noted that those recommendations were mainly for cytotoxic chemotherapy induction and consolidation treatments.

With the many changes in up-front therapy, institutions are updating treatments and evaluating emerging trends in research for CNS. At the University of Texas MD Anderson Cancer Center, clinicians are using intrathecal chemotherapy given with the induction and consolidation treatment for patients.

“We’ve recently increased the number of intrathecal prophylaxis [therapies] that we give based on changes in the up-front therapy. Generally, when we were giving 8 intrathecal therapies for certain groups of patients, we’ve increased that recommendation to 12,” Kebriaei said.

For example, especially for older patients with Ph-positive ALL, newer regimensinclude much less methotrexate and cytarabine, or omit them altogether, using instead a combination of immunotherapy and tyrosine kinase inhibitor. The number of intrathecal therapies in these patients may need to be increased.

“For those patients who are getting a chemotherapy-free regimen—currently the older patients [with] Ph-positive [disease] who may be getting a regimen [such as] blinatumomab [Blincyto®; Amgen] and dasatinib [Sprycel®; Bristol-Myers Squibb] or blinatumomab and ponatinib [Iclusig®; Takeda Pharmaceuticals]—we should think about giving at least 8 intrathecal therapies. At MD Anderson [Cancer Center], we’re recommending 12.”

According to Kebriaei, there remains an unmet need to study the question of whether recommendations for CNS prophylaxis should be changed. She believes that institutions will soon focus more on immunotherapy-based regimens and chemotherapy-free regimens.

Another important question asked about up-front treatment should include what the optimal CNS prophylaxis should be, because experts do not yet have a definitive answer. “At MD Anderson [Cancer Center], the recommendation now to give 12 intrathecal therapies is reasonable based on the adjustments that we’ve made in the up-front therapy. We may be overtreating a small number of patients. That’s where [findings from] the prospective studies would be helpful to inform that recommendation,” Kebriaei said.

References

1. Wu SY, Short NJ, Nasr L, Dabaja BS, Fang PQ. Central nervous system prophylaxis and treatment in acute leukemias. Curr Treat Options Oncol. 2022;23(12):1829-1844. doi:10.1007/s11864-022-01032-5

2. Paul S, Short NJ. Central nervous system involvement in adults with acute leukemia: diagnosis, prevention, and management. Curr Oncol Rep. 2022;24(4):427-436. doi:10.1007/s11912-022-01220-4

3. Ghione P, Lewis KL, Bobillo S, et al. Central nervous system lymphomas-assessment and treatment and prevention of central nervous system relapse. Hematol Oncol. 2023;10.1002/hon.3197. doi:10.1002/hon.3197