Paul Richardson, MD
In the past 20 years, we’ve been very fortunate in the development of effective myeloma therapies and have seen remarkable progress for our patients. Median survivals have improved from 2 to 3 years—at best—to 3 to 5 years with transplant for younger patients, and now we’re seeing median survivals in excess of 10 years, with long-term, durable remissions in an increasing proportion of patients. This speaks volumes to the progress made against a hitherto incurable and otherwise deadly disease. While this expansion of therapeutic opportunity has been incremental in some ways, it’s been continuous and, when seen in aggregate, the impact is considerable.
For example, in the past several years there have been numerous advances specifically in relapsed and refractory multiple myeloma. Perhaps the most important has been the introduction of monoclonal antibodies—in particular, the first-in-class monoclonal antibody daratumumab (Darzalex), which targets CD38, isatuximab in the same class, and elotuzumab (Empliciti), particularly when combined with immunomodulators. Elotuzumab is involved in the activation of natural killer cells and the engagement of a receptor, SLAMF7, that is uniquely expressed in myeloma, and distinct from CD38. In terms of the pipeline, the CD38 space continues to be promising given the current successes with isatuximab. In the same context, we have very exciting new constructs such as antibody–drug conjugates, including GSK’916 (GSK2857916), a particularly active agent under development targeting BCMA that has shown evidence of efficacy as both a single agent and in combination.
Beyond the monoclonal antibodies, we have continued significant progress with already approved next-generation immunomodulatory therapy in the form of pomalidomide (Pomalyst) and next-generation proteasome inhibition in the form of both carfilzomib (Kyprolis) and ixazomib (Ninlaro). Highly potent immunomodulatory agents called Cell-Mods are showing impressive activity and tolerability in early studies even after pomalidomide and monoclonal antibody treatment failure (specifically, the oral agents CC9220 and CC9480).
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