Pomalidomide and HDAC Inhibitors in Multiple Myeloma

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Pomalidomide is third in the family of immunomodulatory drugs (IMiDs), says Jeffrey A. Zonder, MD. It is currently used in patients who have relapsed after receiving another IMiD and a proteasome inhibitor. Pomalidomide can be utilized in older patients who may have relapsed on treatment with lenalidomide plus dexamethasone, Shaji Kumar, MD, comments. Additionally, combination strategies are intriguing.

Data have shown that nearly 80% of lenalidomide-refractory patients respond to the combination of pomalidomide, bortezomib, and dexamethasone. Additionally, the combination of pomalidomide with doxorubicin and dexamethasone in lenalidomide-refractory patients has demonstrated promise, James R. Berenson, MD, adds.

Histone deacetylase (HDAC) inhibition represents another promising approach for patients with multiple myeloma. The FDA approved the first HDAC inhibitor, panobinostat, in combination with bortezomib and dexamethasone in late February, based on a prespecified subgroup analysis from the phase III PANORAMA-1 trial. In this 193-patient analysis, the median progression-free survival with panobinostat was 10.6 months versus 5.8 months with placebo (HR = 0.52). Additionally, the tumor shrinkage rate with panobinostat was 59% versus 41% with bortezomib and dexamethasone alone.

Panobinostat was approved with a Boxed Warning and a Risk Evaluation and Mitigation Strategy regarding severe diarrhea and severe and fatal cardiac events, arrhythmias and electrocardiogram (ECG) changes. Although side effects can be a concern, Sagar Lonial, MD, comments that the HDAC drug class is an active and effective class when combined with proteasome inhibitors or IMiDs.