German Agency Questions Benefit of Empliciti Reported in Multiple Myeloma Study

Empliciti (elotuzumab), a monoclonal antibody, is approved in both the U.S. and Europe as a treatment, in combination with Revlimid (lenalidomide) and Decatron (dexamethasone), for multiple myeloma patients who have received at least one prior treatment. But the German Institute for Quality and Efficiency in Health and Care (IQWiG) announced  that an early benefit assessment was unable to prove an added benefit for the triple combination therapy known as ERD, in comparison to Revlimid plus Decatron (RD) as treatment.

The IQWiG decided that data from Phase 3 study, ELOQUENT-2, “was unsuitable for answering this research question [added benefit],” according to a report in Science Daily. The IQWiG said that the dosage used for Decatron as a comparator drug was too low, and the recommended dosing schedule was not followed in the trial’s RD arm, which may have influenced study results.

The ongoing clinical trial (NCT01239797) is a randomized, open-label study designed to assess the safety and efficacy of Revlimid plus Decatron with or without Empliciti in treating patients with relapsed or refractory multiple myeloma. In December 2015, researchers presented two-year follow-up data of ELOQUENT-2 at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, showing significant improvements in progression-free survival and response rates.

Bristol-Myers Squibb and AbbVie  also submitted data from ELOQUENT-2 to the Federal Joint Committee (G-BA), in Germany. In addition to Revlimid in combination with Decatron as an appropriate comparator therapy for the study, the G-BA also considered Velcade (bortezomib) monotherapy, or two Velcade combinations, to be appropriate.

But in the case of the Revlimid and Decatron combination, the dosing scheme of Decatron depended on the respective combination:

• when in combination with Empliciti and Revlimid, a lower dose of Decatron should be used than in combination with Revlimid alone
• pulsed administration of Decatron (four days of Decatron alternate with four days without the drug in the first four cycles) is only required in combination with Revlimid, but not in the triple combination

However, the dosing scheme in the control arm deviated from such recommendations, with the participants receiving only one-third of the required dose of Decatron, and without pulsed administration, IQWiG said.

The German agency therefore believes that the dose of Decatron was so low that AbbVie was essentially comparing Emplicity with placebo, in combination with basic therapy. Since the specifications of the appropriate comparator therapy were not followed, the added benefit of Emplicity in combination with Revlimid and Decatron, in comparison with the dual combination, cannot be proven.

“It is not possible to estimate whether and in which direction this deviation from the approval-compliant dosing scheme influenced the study results,” they wrote in their executive summary.