SPOTLIGHT percent of all cases (473). DLBCL often develops from evolution of other types of lymphoma, including follicular lymphoma, that have been undergoing therapy. Different subtypes of DLBCL exist. When a patient does not fit into any of those subtypes, it is classified as DLBCL not otherwise specified. Epcoritamab-bysp was approved by FDA in May 2023 for patients with either DLBCL not otherwise specified or high-grade B-cell lymphoma whose disease did not respond to or relapsed following two or more lines of systemic therapy. The approval was based on results from a phase I/II clinical trial which showed that 61 percent of patients responded to the therapeutic and 38 percent of patients achieved complete responses with no signs or symptoms of cancer following the treatment. The approval of epcoritamabbysp includes a warning that the treatment can cause serious or life-threatening immune-related adverse reactions and should only be administered by qualified health care professionals with appropriate medical support. Glofitamab-gxbm was approved in June 2023 for patients with DLBCL, not otherwise specified or large B-cell lymphoma arising from follicular lymphoma, who relapsed after or did not respond to two or more lines of systemic therapy. The approval was based on data from a phase I/II study in which more than half of all patients responded to the treatment, with approximately 40 percent achieving complete responses, meaning researchers could not detect signs or symptoms of cancer (474). Glofitamab-gxbm has a few unique characteristics that set it apart from the other T-cell engaging bispecific antibodies discussed in this section. First, glofitamab-gxbm is approved to be administered for a fixed duration of about 8.5 months, whereas most other agents are administered until the disease progresses or the therapeutic cannot be tolerated any longer. The fixed-duration approach is used because data indicate that administration until disease progression is not required to achieve a durable remission with glofitamab. The fixed-duration approach is attractive to patients because it provides them with a shorter and potentially less toxic treatment option. Second, glofitamab-gxbm has two arms to latch onto CD20 unlike epcoritamab-bysp and mosunetuzumab-axgb, which only have one, and is therefore expected to be more potent. The approval of glofitamab-gxbm includes a warning that the treatment can cause serious or life-threatening immune-related adverse reactions and should only be administered by qualified health care professionals with appropriate medical support. While ongoing research is needed to identify ways to minimize the adverse effects, T-cell engaging bispecific antibodies are now offering a wide selection of new therapeutics and providing hope to many patients with advanced cancer who are often out of options and urgently need effective treatments for their rapidly progressing disease. Another group of therapeutic antibodies that mark cancer cells for elimination by the immune system uses a natural process called antibody-dependent cellular cytotoxicity. When the immune system detects a pathogen or damaged cells, B cells produce antibodies that flag unwanted cells or organisms, which are then recognized and killed by immune cells such as NK cells (see Sidebar 38, p. 100) (475). Researchers are using this knowledge to develop antibodies that bind to specific targets on cancer cells and invoke antibody-dependent cellular cytotoxicity to kill them. Many therapeutic antibodies that work this way have been approved by FDA and are benefiting numerous patients with different cancer types including solid tumors, hematologic cancers, and pediatric cancers. As one example, dinutuximab (Unituxin), which was approved in 2015 for treating children with highrisk neuroblastoma, works by attaching to a protein, GD2, on neuroblastoma cells and flagging them for destruction by immune More than 130 bispecific antibodies are currently being evaluated globally as anticancer therapeutics. Sixty seven percent of these are being tested in solid tumors, 24 percent in blood cancers, and 9 percent in both (332). IMMUNOTHERAPEUTICS APPROVED BY FDA IN THE PAST FIVE YEARS THAT INVOKE ANTIBODYDEPENDENT CELLULAR CYTOTOXICITY 2018 mogamulizumab-kpkc Targets CCR4 to treat certain type of leukemia 2020 isatuximab-irfc Targets CD38 to treat multiple myeloma tafasitamab-cxix Targets CD19 to treat certain type of lymphoma margetuximab-cmkb Targets HER-2 to treat certain type of breast cancer naxitamab-gqgk Targets GD2 to treat neuroblastoma AACR Cancer Progress Report 2023 Immunotherapy: Pushing the Frontier of Cancer Medicine 124
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