FDA Weighs in On Immune Therapies

  • November 08, 2018

    FDA Weighs in On Immune Therapies

    WRITTEN BY: Miko Santos
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On Wednesday, November 7, the U.S. Food and Drug Administration (FDA) announced the approval of elotuzumab (Empliciti®) by intravenous injection in combination with pomalidomide and dexamethasone (EPd) for treatment of relapsed or refractory myeloma in patients who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor. This is obviously excellent news for patients!

Combination yields excellent results

Patients given the EPd combination in the ELOQUENT-3 randomized trial, which compared EPd with Pd alone, experienced excellent benefits and no unexpected safety signals. In the study of 117 patients with relapsed or refractory myeloma, the progression-free survival (PFS: remission length) was 10.3 months with EPd versus 4.7 months with Pd alone.  The overall response rate (ORR: >50% reduction in myeloma protein level) was also improved (53.3% versus 26.3%). The number of patients achieving very good partial response (VGPR: 90% or greater reduction in myeloma protein level) was 20% versus 8.8%. No new safety signals emerged, and the occurrence of infusion reactions was minimal.

In summary, this new EPd regimen is an important option for patients with relapsed or refractory myeloma. In addition, the tolerance and safety are particularly encouraging.

The results of ELOQUENT-3 were published in The New England Journal of Medicine (NEJM) simultaneously with the FDA approval.  In the same issue of NEJM, another article warns of the unanticipated toxicities that can occur in myeloma patients when immunotherapies are combined. Drs. Nicole Gormley and Richard Pazdur of the FDA discuss uncertainties about new immunotherapies in myeloma related primarily to the use of pembrolizumab (brand name Keytruda®), a PD-1 inhibitor (programmed cell-death inhibitor).  In “Immunotherapy Combinations in Multiple Myeloma—Known Unknowns,” the authors stress that in this new era, careful scrutiny of new immunotherapy combinations is required.

FDA cautions about new immunotherapy combinations

Fortunately, EPd is an effective and safe combination. However, unexpected toxicities with the pembrolizumab Pd combination raised a red flag about potential new risks with novel combinations. In their article, Drs. Gormley and Pazdur discuss in detail what happened with pembrolizumab, including the safety alert and the hold placed on all myeloma clinical trials in which pembrolizumab was combined with a thalidomide analogue (Revlimid® or Pomalyst®) because of serious heart, lung, and other toxicities. They note that more elderly and/or frail myeloma patients may be at a greater risk of complications. Also, since myeloma itself is associated with significant immune dysfunction, greater caution is required to assess the impact of powerful new combinations in both the shorter and longer term. Specific guidance is given for future early trials to avoid potential problems in larger randomized studies.

Bottom line

Great news about the EPd combination—but experts caution that careful evaluation of each new combination is required to avoid expected toxicities.


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