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Author: Admin | 2025-04-28
2017).Anti-PD1 and anti-PDL1 antibody drugs The immune system plays an important role in tumor eradication. Cells within the immune system express receptors (called immune checkpoint receptors) that balance the stimulatory and inhibitory immune responses. In many cancers, the tumor cells express molecules that preferentially activate the inhibitory receptors on immune cells, resulting in a suppressed immune response. The checkpoint inhibitor drugs, anti-PD1 and anti-PDL1 MAbs have been designed to block the tumors from inhibiting the immune system. It essentially “takes the brake off” the immune system. Two anti-PD1 MAbs (Keytruda and Opdivo) and 3 anti-PDL1 MAbs (Tecentriq, Bavencio and Imfinzi) have been approved for several solid cancers such as skin cancers, lung cancers and urothelial cancers. Given the robust activity of these drugs in other cancers, these MAbs are being studied in combination with standard therapy in multiple myeloma (www.clinicaltrials.gov).Venetoclax (ABT-199) Normal cells have a balance of proteins which promote cell survival and proteins which promote cell death. Myeloma has an imbalance of these proteins resulting in cancer cell survival. Anti-death proteins such as BCL2 support the survival of myeloma cells. Venetoclax inhibits BCL2. This drug is currently approved for a different cancer, chronic lymphocytic leukemia. Early studies of venetoclax in myeloma especially myeloma cells which harbor the genetic change, translocation 11;14. This drug is currently being tested in a Phase 3 clinical trial in combination with bortezomib and dexamethasone for myeloma patients (www.clinicaltrials.gov).Newer proteasome inhibitors Marizomib, a second generation irreversible pan-proteasome inhibitor, showed some activity in an early phase clinical trial (Richardson et al. 2016, 2693-2700) and is now being studied in combination with pomalidomide and dexamathasone for patients who were resistant to lenalidomide and bortezomib (www.clinicaltrials.gov). Another proteasome inhibitor in development, oprozomib is an oral drug related to carfilzomib. Efficacy was seen and now it is being studied in combination with pomalidomide and dexamethasone in patients with refractory myeloma (www.clinicaltrials.gov).Selinexor Selinexor is a selective inhibitor of nuclear export (SINE) compound which functions by inhibiting XPO1, a nuclear export protein. Tumor suppressor proteins become trapped in the cell nucleus, which leads to myeloma cell death. This drug has shown activity in combination with carfilzomib and dexamethasone in an early phase study. Currently selinexor is being studied in combination with dexamethasone for the treatment of myeloma patients. Another clinical study to evaluate the combination of selinexor, carfilzomib and dexamethasone versus carfilzomib and dexamethasone in patients with myeloma is currently also
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