First bite syndrome chemotherapy2/3/2024 To put this into perspective, this response rate is about twice the rate observed with single-agent anti-CD38 therapy. Interestingly, response rates range from 60% to 70% when given at the recommended phase 2 dosing, they generally occur by 1 to 2 months, and they appear durable albeit thus far without long follow-up. These agents have shown a low incidence of severe CRS and neurotoxicity, effects that are generally limited to the initial step-up dosing. Analogous to the lymphoma BiTEs, these medications are given via step-up dosing, initially intravenously, but increasingly via subcutaneous administration. Cevostamab is targeted to FcRH5, a marker specific for B lymphocytes and plasma cells. 16 Talquetamab is directed to GPRC5D, an antigen that is generally highly expressed on myeloma but not on normal plasma cells or other cells. 15-20 Thus far, the target for most of the myeloma BiTEs is B-cell maturation antigen (BCMA), with the notable exceptions of talquetamab (GPRC5D) 15 and cevostamab (formerly BFCR4350A). It seems likely that BiTEs will further advance the goal of a chemotherapy-free strategy in B-cell lymphomas.īiTE therapy is also likely to soon further expand the immunotherapy armamentarium for multiple myeloma ( Table 3). As an example, in a phase 3 trial, epcoritamab (GEN3013) is being tested vs investigator’s choice of therapy for transplant-ineligible patients with relapsed disease, and mosunetuzumab (RG7828) will be offered as initial therapy for patients with indolent follicular and marginal cell lymphomas. ![]() 11,13,14Īs was the case of blinatumomab in ALL, BiTE therapy lymphoma trials are migrating to earlier treatment including in combination with standard therapy or even in-lieu of conventional treatment ( Table 1). In fact, preliminary reports of the BiTE agents presented at the ASH Annual Meeting in 20 describe durable responses after failure of CAR T-cell therapy. 11-14 Thus far, as the BiTE drugs furthest along in development for B-cell lymphoma are directed to CD20 compared with the CD19 target used in the approved CAR T-cell products, sequential therapy with CAR T cells and BiTEs is feasible. There is considerable enthusiasm that BiTEs may have a similar impact in lymphoma as has been observed in ALL and may even compete with CAR T cells ( Table 1). More recently, blinatumomab is being incorporated into frontline therapy for Philadelphia chromosome (Ph)–negative B-cell ALL 9 and as part of a chemotherapy-free strategy for Ph-positive ALL. 7 Subsequently, the agent has been recognized for its remarkable activity in converting minimal residual disease–positive ALL to negative status, 8 possibly decreasing the need for allogeneic transplant. The model for BiTE therapy is the anti-CD19 X anti-CD3 drug, blinatumomab (Blincyto), which was first approved because it outperformed standard therapy in relapsed acute lymphoblastic leukemia (ALL). 4-6 More recently, bispecific T-cell engager (BiTE) therapy is poised to make an impact in the setting of relapsed/refractory B-cell lymphoma for both indolent and aggressive disease, including those who relapse after CAR T-cell therapy.īiTE therapy is an immunotherapy that works by serially killing tumor cells by placing them in proximity to T cells. This progress has come in the form of a new antibody, tafasitamab, 1 2 antibody-drug conjugates 2,3 and most notably, 3 CAR T-cell therapy products that have been shown to result in approximately 40% of patients achieving durable remission and possible cure. ![]() Despite the failure of several strategies to improve the outcomes of patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL), there appears to be substantial and growing progress in the treatment of relapsed disease.
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