Checkpoint Inhibition in Non-Hodgkin's Lymphoma

Abstract

As patients continue to die from malignant lymphoma, novel treatment options continue to be warranted. To successfully grow and spread, tumor cells need to escape the immune system; therefore, the augmentation or restoration of immune effectors against the malignant cell could be of great value, as shown, e.g., for allogeneic transplantation. A deepened understanding of the regulation of activation and inhibition of the T cell-based effector mechanisms has led to the development of drugs that are able to modify specific checkpoints of this system and thereby raise an immune response against tumor cells. With dramatic responses observed in Hodgkin's disease (HD), interest has risen to explore these drugs in non-Hodgkin's lymphoma (NHL). Available data underline the potential of checkpoint inhibitors in a variety of lymphoma entities, such as primary mediastinal B cell lymphoma (PMBCL) or central nervous system (CNS) lymphoma, and there is hope that a significant proportion of patients will finally benefit. However, intensive efforts are needed to develop optimal screening tools, combinations, and sequences to explore the full potential of these new classes of therapeutic agents.

Immune checkpoints in hematologic malignancies: What made the immune cells and clinicians exhausted!

“…These studies indicate that HTLV1-specific CTLs play an important role in suppressing the proliferation of HTLV1-infected and transformed T cells and thereby preventing ATLL development (Arnulf et al, 2004;Kannagi et al, 2005). Intriguingly, in individuals carrying all three HTLV1, CMV, and EBV viruses, HTLV1-specific T cells showed greater exhaustion than those specific for either CMV or EBV, confirming the broad immunosuppression seen in patients with ATLL (Heß, 2017). PD1/PDL1 pathway blockade in these studies increased T-cell responses and reversed their dysfunctional state (Kozako et al, 2009;Shimauchi et al, 2007).…”

“…Moreover, because of the high potential of hematologic malignancies to become drug-resistant (Heß, 2017), early initiation of treatment with checkpoint blockers should be rapidly considered in these patients.…”

“…Studies should also compare these treatments with current and standard therapies to better judgment of their efficacy. Moreover, because of the high potential of hematologic malignancies to become drug‐resistant (Heß, 2017), early initiation of treatment with checkpoint blockers should be rapidly considered in these patients.…”

How I manage autoimmune cytopenias in patients with lymphoid cancer

“…Immune-checkpoint inhibitors have hematologic as well as non-hematologic autoimmune side effects. [82][83][84] Finally, novel cellular therapies like CAR-T cell treatment against CD19 can cause prolonged cytopenias not attributable to late effects of chmotherapy or lymphodepletion. This should be differentiated from late myelodysplastic syndrome.…”

“…Immune checkpoint inhibitors have hematologic and nonhematologic autoimmune side effects. 80 , 81 , 82 …”