The past several decades have witnessed a dramatic improvement in the treatment of patients with multiple myeloma (MM), the second most common type of hematologic malignancy. A better understanding of the biology of this disease and the introduction of a wealth of novel drug classes has more than doubled median survival times. In a single month in 2015, the FDA approved 3 new drugs, each with a unique mechanism of action.
Although they are dubbed IMiDs, these drugs have a wide range of cellular effects, many of which were recently tied together by the discovery of their shared mechanism of action. In a noteworthy development, researchers now believe that IMiDs represent the first clinically approved agents in a novel class of drugs, targeting an enzyme involved in the regulation of protein levels in the cell. This understanding opens the door to a unique drug mechanism that could expand the reach of our anticancer armamentarium to targets previously thought to be undruggable.
Table. Experimental IMiD Combination Regimens in Selected Ongoing Clinical Trials
ABC indicates activate B-cell; AML, acute myeloid leukemia; CLL, chronic lymphocytic leukemia; DLBCL, di use large B-cell lymphoma; FL, follicular lymphoma; HCC, hepatocellular carcinoma; IMiD, immunomodulatory drug; MCL, mantle cell lymphoma; MM, multiple myeloma; MZL, marginal zone lymphoma; R-CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone; SLL, small lymphocytic leukemia.
Rewriting a Turbulent History
Thalidomide is infamous for the disastrous teratogenic effects that manifested themselves as severe birth defects in thousands of newborn babies after it was used to ease morning sickness in pregnant women in the 1950s. Although its anticancer properties were noted at the time, it wasn’t until the 1990s that it was reinvented as an IMiD when its anti-inflammatory properties were revealed.
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