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Description:
While the Nobel prize for development of monoclonal antibodies by fusion of multiple myeloma (MM) cells with mouse derived spleen cells was awarded in 1984, there were no therapeutic antibodies for the treatment of myeloma for over 30 years. Since 2015, there has been an explosion in the investigation of immunotherapeutic approaches – both humoral and cellular strategies. In spite of an arsenal of 7 currently available classes of anti-MM therapies, there remain many unmet medical needs (eg patients who are genomically and functionally high risk, multidrug refractory, frail elderly) and it will be exciting to see if immunotherapeutic strategies can help fill these voids.Â
Dr Niels Van de Donk will discuss treatment selection and sequencing, which becomes increasingly complex with the increasing number of therapeutic options. The choice of treatment is dependent on both patient- and tumor-related factors. Treatment-related factors, such as type and response to prior therapy are also critical in terms of the selection of a new treatment regimen. The increasing use of CD38 antibodies in newly diagnosed and early relapsed/refractory MM, raises questions, including subsequent retreatment with CD38 antibodies. With the introduction of new immunotherapies with novel modes of action, sequencing should also take into account the effect of prior therapy on immune function.
Dr Eric Smith will outline B Cell membrane antigen (BCMA) targeted chimeric antigen receptor (CAR)-T cell therapy for MM, which induces frequent and deep responses in heavily pre-treated patients, however relapse is still far too common. After reviewing emerging clinical data, potential mechanisms of resistance will be explored, including T cell intrinsic and tumor cell mediated. Some of these resistance factors will be specific to targeting BCMA, while others are broadly applicable. Potential strategies in late pre-clinical or early clinical development aimed at addressing the underlying biology that leads to sub-optimal responses will also be discussed.Â
Dr Chari will discuss other known MM antigens that may serve as effective therapeutic targets for naked antibodies and several such agents are in development. Some of these cell surface antigens are also internalized, making them ideal candidates for antibody–drug conjugates (ADC) such as belantamab mafodotin, conjugated with auristatin F and targeting BCMA. An entirely novel class of agents are the T cell redirecting agents with the majority being bispecific monoclonal antibodies that simultaneously bind CD3 on T cells and a myeloma antigen. Bispecifics targeting the MM antigens BCMA and GPRC5d have already demonstrated deep and durable responses in heavily pretreated patients. Bispecifics targeting CD38 and FCHR5 as well as trispecifics are under investigation.
Dr Niels Van de Donk will discuss treatment selection and sequencing, which becomes increasingly complex with the increasing number of therapeutic options. The choice of treatment is dependent on both patient- and tumor-related factors. Treatment-related factors, such as type and response to prior therapy are also critical in terms of the selection of a new treatment regimen. The increasing use of CD38 antibodies in newly diagnosed and early relapsed/refractory MM, raises questions, including subsequent retreatment with CD38 antibodies. With the introduction of new immunotherapies with novel modes of action, sequencing should also take into account the effect of prior therapy on immune function.
Dr Eric Smith will outline B Cell membrane antigen (BCMA) targeted chimeric antigen receptor (CAR)-T cell therapy for MM, which induces frequent and deep responses in heavily pre-treated patients, however relapse is still far too common. After reviewing emerging clinical data, potential mechanisms of resistance will be explored, including T cell intrinsic and tumor cell mediated. Some of these resistance factors will be specific to targeting BCMA, while others are broadly applicable. Potential strategies in late pre-clinical or early clinical development aimed at addressing the underlying biology that leads to sub-optimal responses will also be discussed.Â
Dr Chari will discuss other known MM antigens that may serve as effective therapeutic targets for naked antibodies and several such agents are in development. Some of these cell surface antigens are also internalized, making them ideal candidates for antibody–drug conjugates (ADC) such as belantamab mafodotin, conjugated with auristatin F and targeting BCMA. An entirely novel class of agents are the T cell redirecting agents with the majority being bispecific monoclonal antibodies that simultaneously bind CD3 on T cells and a myeloma antigen. Bispecifics targeting the MM antigens BCMA and GPRC5d have already demonstrated deep and durable responses in heavily pretreated patients. Bispecifics targeting CD38 and FCHR5 as well as trispecifics are under investigation.