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. Author manuscript; available in PMC: 2015 Jun 26.
Published in final edited form as: Blood Rev. 2014 Sep 28;29(2):81–91. doi: 10.1016/j.blre.2014.09.011

Table 4.

Future challenges to the application of antibody-based therapies to myeloma.

Challenges Clinical relevance Research objectives to be addressed
Target expression on
M-IC		 Finding curative potential

  1. M-IC characterization & clarification of published discrepencies (M-IC markers may vary patient–patient).

  2. Characterize antigen of interest in (various) population(s) of M-IC.
Ideal drug
combinations		 Finding synergism and avoiding antagonism

  1. Study antigen expression in vitro with proteasome inhibitors, IMiDs and steroids.

  2. In vivo animal model assessment of agent in combination with standard drugs.
Disease setting Utility in relpased, refractory or newly
diagnosed disease

  1. Clinical need in relapsed disease where resistance to current agents has evolved.

  2. Patients with high risk and/or refractory myeloma, such as patients with deletion of 17p and plasma cell luekemia.

  3. Potential for cure (or deeper remission) in standard induction regimens with or without autologous stem cell transplant.
Optimization of ADCs Maximizing efficacy

  1. Selection of ideal antigens for this modality (e.g. internalization kinetics, expression level and pattern).

  2. Companion biomarker development (e.g. immunohistochemistry, flow cytometry).

  3. Incorporation of linker and payload technology improvments.

ADC = antibody–drug conjugate, M-IC = myeloma initiating cells.