Antibody drug conjugates for the treatment of multiple myeloma

• Published in: American journal of hematology 2023-03, Vol.98 (S2), p.S22-S34
• Main Authors: Leong, Sarah, Lam, Ho Pui Jeff, Kirkham, Zoe, Popat, Rakesh
• Format: Article
• Language: English
• Subjects: Antibodies; Clinical trials; Hematology; Humans; Immunoconjugates - adverse effects; Immunotherapy; Multiple myeloma; Multiple Myeloma - drug therapy; Secretase
• ISSN: 0361-8609; 1096-8652
• DOI: 10.1002/ajh.26750

The treatment landscape of multiple myeloma (MM) has evolved substantially, but it remains largely incurable so new treatment options are required. Antibody drug conjugates (ADCs) are an emerging therapeutic class used in Cancer to deliver targeted therapy. ADCs are composed of three components, an antibody, a chemical linker and a payload which must be chosen carefully to be effective and safe. This alternative mechanism of action to standard treatments makes ADCs an attractive class for further development. However, several ADCs have been investigated but many have not moved further than phase 1 trials, highlighting the challenges in designing an effective and tolerable ADC. Belantamab Mafodotin is currently the only ADC licensed for MM although others are currently under evaluation. Belantamab Mafodotin demonstrated efficacy as monotherapy in triple class exposed patients and combinations are under development which maintain safety with encouraging efficacy particularly at earlier lines of therapy. Retaining an acceptable adverse event profile for ADCs remains vital for their success. Strategies to mitigate ocular events for Belantamab Mafodotin involve lower and less frequent dosing as well as the use of gamma secretase inhibitors. The optimal sequencing of ADCs within the treatment pathway including novel immunotherapies is now under evaluation. Antibody drug conjugates (ADCs) are an emerging class of drugs which can deliver targeted therapy to multiple myeloma (MM) cells. They are composed of three main components: an antibody, a chemical linker and a payload. Several ADCs have been developed but not progressed further than phase 1 trials, highlighting the challenges in developing a safe and effective ADC. In this article, we review the development of this class of drugs in MM, including Belantamb Mafodotin, the only licensed ADC for MM which has shown to be effective as a monotherapy and in combination with other agents. We focus on the class specific toxicity of ocular toxicity and its management. We explore the potential issues of ADC resistance and the optimal sequencing of ADCs within the treatment pathway including other novel immunotherapies.