Immunotherapy and Allogeneic HSCT: Unleashing Your Patient's Immune System Safely

“Mary

Mary E. DiLorenzo, MSN, RN-C, NP-C

Our immune system’s successful detection and destruction of abnormal cells is the hallmark of our body’s ability to either stop a malignancy from occurring or halt it once it has begun. However, cancer cells are sometimes able to evade one’s natural defense mechanism, thus allowing proliferation and manifestation of a particular disease to occur. Therefore, it comes as no surprise that cancer therapies are increasingly more focused on immunotherapy and the use of targeted agents to directly “unleash” a patient’s immune system in an attempt to slow down or terminate production of cancer cells in the host.

One immunotherapy approach is to block the ability of certain proteins, called immune checkpoint inhibitors, to limit the strength and duration of the immune reactions. These proteins normally keep immune responses in check by preventing overly intense reactions that might damage or destroy normal cells as well as abnormal cells. However, research has proven that certain tumor cells can take control of these proteins and use them to suppress the body’s natural immune responses.

Blocking the activity of immune checkpoint proteins releases the “brake” on the immune system, increasing its efficacy to destroy malignant cells. One such agent that has been recently FDA-approved in the treatment of classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation brentuximab vedotin is nivolumab (Opdivo).

Nivolumab is a human monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Binding of these ligands to the PD-1 receptor found on T cells, inhibits T cell proliferation and cytokine production. Nivolumab binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, thus preventing the inhibition or “brake” on the immune response, resulting in an antitumor immune response and decreased tumor burden.

Thus, one may be tempted to say that this is the perfect solution to an imperfect scenario; however, when discussed within the context of allogeneic stem cell transplantation, red flags regarding potentially life-threatening complications must be addressed.

Although allogeneic HSCT has revolutionized the manner in which providers view the interplay between hematologic malignancies and their appropriate therapeutic treatment options, one would be remiss to ignore the fact that an all-too-common complication of donor HSCTs, known as graft versus host disease (GVHD), potentially limits the use of certain immune-modulating agents, or at the very least, heightens awareness of their side effect profile.

The pathophysiology behind GVHD can be compared to an overactive or “brake-less” immune response, in which donor-derived T-cells attack the host and produce a multitude of sequelae, ranging from those which are relatively responsive to initial corticosteroid therapy, to ones that are refractory and the driver of possibly life-threatening complications.

Therefore, the decision to use checkpoint inhibitors in the context of allogeneic HSCT must be done while taking into consideration the possible interplay between the known mechanism of action of the drug as well as the potential complication known as GVHD—a net result being a host’s immune system that is “unhinged” and indiscriminately attacks both nonmalignant and malignant cells.

Providers must choose patients wisely, analyzing a patient’s comorbid conditions eg, Crohn’s disease, ulcerative colitis, lupus, pulmonary/liver disease, and drug profile history (specifically any drug that weakens the immune system) eg, antithymocyte globulin, corticosteroids, and calcineurin inhibitors, that would predispose them to developing more severe complications.

Nurses must be diligent in systematically monitoring for adverse events including, but not limited to: hyperacute GVHD, severe acute GVHD, hepatic veno-occlusive disease, pneumonitis, colitis, hepatitis, adrenal insufficiency, encephalitis, as well as other immune-mediated adverse reactions.

As advances in immunotherapy and allogeneic HSCT occur, it is the ethical responsibility of every healthcare provider to educate him or herself on the latest FDA drugs available to treat such aggressive malignant conditions, while at the same time remember that once a host’s natural immune system has been given the “green light,” a necessary and effective “red light” must be ready and available for use in the provider’s arsenal. It is then that patients will have been given the most effective and safe therapy to treat their specific disease.

Mary E. DiLorenzo, MSN, RN-C, NP-C, is an advanced practice nurse in the Blood and Marrow Transplantation Program at John Theurer Cancer Center in Hackensack, New Jersey.