SPOTLIGHT a molecule that is abundant on the surface of most multiple myeloma cells, with the second arm. By attaching to these molecules on different cells, teclistamab-cqyv brings the two cell types together, directing the T cells to home in on the myeloma cells. As a result, T cells are activated and they destroy the adjacent myeloma cells. The FDA approval of teclistamab-cqyv was based on data from a phase I/II clinical trial that evaluated the immunotherapeutic in 110 patients who had stopped responding to at least three classes of drugs prior to receiving teclistamab-cqyv (470). More than 60 percent of participants responded to therapy with teclistamabcqyv (470). Historically, patients with multiple myeloma that has progressed following multiple classes of treatment have been extremely challenging to treat. In fact, with immunotherapeutics such as daratumumab, which is approved for these patients, response is seen only in 30 percent of patients or fewer (471). Therefore, the approval of teclistamab-cqyv brings hope to patients like Cindy Brown, p. 122, by providing them with a new and effective treatment option. It is important to note that some of these immunotherapeutics can have life-threatening side effects if not managed immediately and appropriately by trained medical professionals. For example, FDA approval of teclistamab-cqyv comes with a warning of life-threatening adverse events, such as cytokine release syndrome and neurologic toxicity, which are usually manageable. Because of these risks, teclistamab-cqyv is available only through a restricted program, called the Tecvayli Risk Evaluation and Mitigation Strategy (REMS). The three other T-cell engaging bispecific antibodies approved by FDA during the 12 months covered in this report—mosunetuzumab-axgb (Lunsumio), epcoritamabbysp (Epkinly), and glofitamab-gxbm (Columvi)—all work by attaching to CD3 on T cells and to CD20, a protein that is found in abundance on the surface of cancerous B cells. By bringing the two cell types together, these therapeutics help activate the T cells to destroy cancerous B cells. Mosunetuzumab-axgb was approved by FDA in December 2022 for the treatment of certain patients with relapsed or refractory follicular lymphoma, the second most common form of NHL diagnosed in the United States. Follicular lymphoma is a slow-growing cancer that arises in immune cells called B cells (see Sidebar 38, p. 100) but can eventually progress to become a fatal disease. Most B cells, including follicular lymphoma B cells, have a protein called CD20 on their surface, making CD20-targeted therapeutic antibodies an attractive treatment option for this cancer. CD20-targeting therapeutic antibodies have been approved previously by FDA for the treatment of follicular lymphoma and have a very high response rate. Rituximab (approved in 2006) and obinutuzumab (approved in 2016) are two examples. However, it should be noted that these antibodies work differently from mosunetuzumab-axgb. Mosunetuzumab-axgb is the first T-cell engaging bispecific antibody approved for follicular lymphoma. The FDA approval of mosunetuzumab-axgb was based on results from a phase I/II clinical trial in which the therapeutic was given to 90 patients with follicular lymphoma that had relapsed or stopped responding to other treatments. All patients had received at least two prior treatments, including a CD20-targeting therapeutic antibody. The results from the trial showed that 80 percent of patients whose disease was not responding to prior treatments had partial or complete tumor shrinkage, with 60 percent exhibiting complete shrinkage following treatment with mosunetuzumabaxgb (472). The complete response rate was significantly higher than that observed with current standard treatments. The approval of mosunetuzumab-axgb comes with a warning for cytokine release syndrome, which may occur as a result of the hyperactivation of T cells that are targeting the lymphoma. Both epcoritamab-bysp and glofitamab-gxbm were approved for the treatment of patients with certain types of NHL. Diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma are types of NHL that arise from B cells. DLBCL is the most common form of the disease, accounting for 30 to 40 As of July 31, 2023, FDA has approved six T-cell engaging bispecific antibodies for the treatment of cancer (469). DECEMBER 2014 blinatumomab (Blincyto) for certain type of leukemia JANUARY 2022 tebentafusp-tebn (Kimmtrak) for uveal melanoma DECEMBER 2022 mosunetuzumab-axgb (Lunsumio) for certain types of lymphoma OCTOBER 2022 teclistamab-cqyv (Tecvayli) for multiple myeloma MAY 2023 epcoritamab-bysp (Epkinly) for certain types of lymphoma JUNE 2023 glofitamab-gxbm (Columvi) for certain types of lymphoma continued on page 124 Immunotherapy: Pushing the Frontier of Cancer Medicine AACR Cancer Progress Report 2023 121
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