Since 2015, the US Food and Drug Administration (FDA) has approved 4 new therapies for the treatment of multiple myeloma: panobinostat, daratumumab, ixazomib, and elotuzumab. In a presentation at the 2016 National Comprehensive Cancer Network Hematologic Malignancies Congress (Sept 30—Oct 1; New York, NY), Carol Ann Huff, MD, Sidney Kimmel Comprehensive Cancer Center (Baltimore, MD), discussed how to best incorporate these new therapeutic options into care regimens.
Panobinostat is a histone deacetylase inhibitor tested in combination with bortezomib and dexamethasone in a phase III trial that included 768 patients with relapsed or refractory multiple myeloma. Initially, there was no significant difference in response rates or overall survival, and so the FDA did not approve the drug. However, a subgroup analysis revealed that patients who received at least two prior lines of therapy did respond, and the drug was approved for that population of patients.
Still, using the drug is not simple, Dr Huff explained, as patients receiving it may experience more severe adverse events. Ongoing studies are examining how to combine panobinostat with other drug types to reduce toxicity. One such drug is the oral proteasome inhibitor ixazomib.
In the phase III TOURMALINE-MM1 trial, ixazomib was combined with lenalidomide and dexamethasone and compared to treatment with lenalidomide and dexamethasone plus a placebo in 722 patients with relapsed or refractory MM who had received 1 to 3 prior lines of therapy. Once again, ixazomib was able to significantly improve median progression-free survival (20 months with ixazomib vs 14.7 with placebo), but toxicity—though manageable—was higher with the study drug.
The remaining two drugs, daratumumab and elotuzumab, are both monoclonal antibodies and part of a new line of treatments called immunotherapies. The Phase II SIRUS trial showed that heavily pretreated patients achieved a near 30% response rate (29.2%) with daratumumab. Likewise, combining daratumumab with dexamethasone and bortezomib led to a progression-free survival rate of 60.7% compared with only 26.9% without the newer therapy. Another trial showed that elotuzumab could also be effective when combined with lenalidomide and dexamethasone, where the addition of the drug improved progression-free survival by almost 5 months.
“These four agents have been incorporated into guidelines for previously treated patients,” Huff concluded. “Our treatment landscape has grown significantly, not just with these but with the ability to combine these with other agents.” She noted that a better understanding of treatment sequences and patient selection, especially in the relapsed/refractory setting, is still needed.