Navigating the Complexities of Immunotherapy in ALL

While immunotherapy has shown great promise in treating acute lymphocytic leukemia (ALL), several challenges remain. Mark Litzow, MD, professor of medicine in the Division of Hematology at Mayo Clinic, discusses some of these in an interview with Targeted Oncology^TM, specifically pertaining to the phase 3 E1910 study (NCT02003222) evaluating blinatumumab (Blincyto).

Some of the main challenges include adverse effects and toxicities like cytokine release syndrome (CRS) and immune effector cell-associate neurotoxicity syndrome (ICANS). Infusion reactions can also happen during or shortly after the immunotherapy drug is given intravenously. Further, some immunotherapies can lower blood cell counts or weaken the immune system, increasing the risk of serious infections. 

Leukemia cells can sometimes lose or reduce the expression of the target antigens (like CD19 or CD22) that immunotherapies are designed to attack, allowing them to evade the treatment. Resistant cells might rely on different signaling pathways for survival and growth, making them less susceptible to the effects of the immunotherapy. Additionally, leukemia cells can develop ways to suppress the immune system's response, preventing the immunotherapy from working effectively. This can involve altering the tumor microenvironment. Genetic changes in the target antigen can also lead to altered protein structures that are no longer recognized by the immunotherapy.

There are also issues of accessibility and cost to consider. Some advanced immunotherapies, like CAR T-cell therapy, are complex to manufacture and administer, making them expensive and not readily available in all centers. 

Ongoing research is focused on addressing these challenges by developing new immunotherapeutic approaches, improving the management of side effects, understanding and overcoming resistance mechanisms, and making these therapies more accessible.