Where Do Programmed Death-1 Inhibitors Fit in the Management of Malignant Lymphoma and correlative primer- read that first
This is a BIG ONE so take your time pay attention and learn the beauty of how researchers across the globe are unraveling the mystery as to how we recognize self as self and yet recognize or fail or are tricked into failing to attach an do damage
- The blockade of immune checkpoints in cancer immunotherapy Among the most promising approaches to activating therapeutic antitumour immunity is the blockade of immune checkpoints. Immune checkpoints refer to a plethora of inhibitory pathways hardwired into the immune system that are crucial for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues in order to minimize collateral tissue damage. It is now clear that tumours co-opt certain immune-checkpoint pathways as a major mechanism of immune resistance, particularly against T cells that are specific for tumour antigens. Because many of the immune checkpoints are initiated by ligand–receptor interactions, they can be readily blocked by antibodies or modulated by recombinant forms of ligands or receptors. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibodies were the first of this class of immunotherapeutics to achieve US Food and Drug Administration (FDA) approval. Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses.
- Author Affiliations
1. Mayo Clinic, Rochester, MN
+ Author Notes
- See accompanying commentaries Corresponding author: Stephen M. Ansell, MD, PhD, Division of Hematology, Mayo Clinic, 200 1st St SW, Rochester, MN 55905; e-mail: email@example.com.
SO HERE IS THAT THE MAYO DID
Tumor-specific cytotoxic T cells have the capacity to target and eradicate malignant B cells in patients with Hodgkin and non-Hodgkin lymphoma; however, multiple mechanisms, including regulatory T cells, immunosuppressive ligands, and immune exhaustion, suppress an effective antitumor immune response. One mechanism that is used by malignant cells to inhibit the immune response is overexpression of programmed death ligand 1 or 2 (PD-L1 or PD-L2) on the cancer cell surface. These ligands interact with the programmed death-1 (PD-1) receptor expressed on intratumoral T cells and provide an inhibitory signal, thereby suppressing the antitumor immune response. Monoclonal antibodies that block PD-1 signaling prevent T-cell inhibition and promote a T-cell–mediated antilymphoma response. Blocking antibodies that are directed against PD-1 or PD-L1 are currently being tested in patients with lymphoma and have shown remarkable efficacy, particularly in patients with relapsed Hodgkin lymphoma. On the basis of the promising activity of this approach, PD-1 inhibitors are being used as single-agent therapy in patients with relapsed Hodgkin lymphoma, and these inhibitors are also being tested in combination with standard chemotherapy or targeted agents in ongoing clinical trials.
Clinical Reviews – Commentary: Targeting Programmed Death 1/Programmed Death Ligand 1 in Lymphoma: A Game Changer
Earlier Palliative Care Consultation Associated With Cost Savings
- Palliative care intervention within 6 days was associated with a 14% reduction in total direct cost.
- Intervention within 2 days was associated with a 24% reduction.
In a prospective cohort study reported in the Journal of Clinical Oncology, May et al found that earlier palliative care consultation for inpatients with advanced cancer was associated with lower total direct costs.
The study included 969 patients with advanced cancer admitted to 5 U.S. hospitals between 2007 and 2011, including 256 seen by a palliative care consultation team and 713 receiving usual care. Overall, palliative care patients had slightly higher total direct costs (mean = $11,150 vs $9,550; median = $7,400 vs $7,379) and longer length of stay (mean = 9 vs 8 days; median = 7 vs 6 days). The study protocol–specified palliative care consultation within 48 hours when possible; 77% of patients in the palliative care group had a consultation within this time frame.
Palliative care intervention within 6 days of hospital admission was associated with a mean reduction in total direct cost of $1,312 (14% reduction) compared with no intervention (P = .04), and intervention within 2 days was associated with a mean reduction of $2,280 (24% reduction; P = .002). Secondary analyses indicated that the cost savings were attributable to a combination of reduced length and intensity of hospital stay, with intervention being associated with reduced laboratory costs irrespective of timing and intervention within 2 days being associated with reduced length of stay and intensive care unit and pharmacy costs.
The investigators concluded: “Earlier palliative care consultation during hospital admission is associated with lower cost of hospital stay for patients admitted with an advanced cancer diagnosis. These findings are consistent with a growing body of research on quality and survival, suggesting that early palliative care should be more widely implemented.”
Peter May, MSc, of Centre for Health Policy and Management, Trinity College Dublin, is the corresponding author of the Journal of Clinical Oncology article.
For full disclosures of the study authors, visit jco.ascopubs.org.