Drugs for Multiple Myeloma, Melanoma Approved in Europe

Nick Mulcahy


May 11, 2016

The European Commission (EC) has approved two new oncology treatments today, one for multiple myeloma and the other for melanoma.

The EC approved elotuzumab (Empliciti, Bristol-Myers Squibb) for the treatment of multiple myeloma and, in a separate decision, approved nivolumab (Opdivo) in combination with ipilimumab (Yervoy) for the treatment of advanced (unresectable or metastatic) melanoma in adults. Both melanoma drugs are from Bristol-Myers Squibb.

Elotuzumab is used in combination with lenalidomide (Revlimid, Celgene) and dexamethasone (multiple brands) in patients who have received at least one previous therapy.

Elotuzumab was approved for the same indication by the US Food and Drug Administration in 2015.

The drug was also recommended for approval in January by European reviewers.

Elotuzumab is the first immune-based therapy to show benefit in the treatment of multiple myeloma. The monoclonal antibody targets the cell-surface protein SLAMF7, which is found on myeloma cells and on natural killer (NK) cells. It offers a two-pronged attack on cancer by targeting myeloma cells directly and by enhancing the ability of NK cells to kill myeloma cells.

"It's a bit of a double whammy," investigator Sagar Lonial, MD, from the Winship Cancer Institute of Emory University in Atlanta, Georgia, said last year, as reported by Medscape Medical News.

As was the case in the United States, the basis for the pending European approval is a trial known as ELOQUENT-2 (NCT01239797), a randomized, open-label clinical study that involved 646 participants with multiple myeloma who had experienced relapse or who had not responded to previous treatment. Results from the trial were published last year (New Engl J Med. 2015;373:621-631).

Coprimary end points were progression-free survival and the overall response rate.

In the published report, the addition of elotuzumab to the combination of lenalidomide plus dexamethasone extended progression-free survival by 4.5 months, compared with treatment with lenalidomide and dexamethasone alone (control group).

Specifically, median progression-free survival in the elotuzumab group was 19.4 months, versus 14.9 months in the control group (hazard ratio [HR] for progression or death in the elotuzumab group, 0.70; P < .001).

After a median follow-up of 24.5 months, the rate of progression-free survival at 1 year in the elotuzumab group was 68% compared with 57% in the control group; at 2 years, the rates were 41% and 27%, respectively.

Additionally, the overall response rate was better in the elotuzumab group than in the control group (78.5% vs 65.5%).

Dr Lonial and his colleagues noted last year that two subgroups of study participants with high-risk features — those with the genetic abnormality del(17p) and those with genetic abnormality t(4;14) — appeared to benefit from elotuzumab as much as average-risk patients. Conventional therapies tend to be less effective in high-risk patients, they explained during a presscast associated with the 2015 annual meeting of the American Society of Clinical Oncology.

The most common adverse events seen with elotuzumab are infusion-related reactions, diarrhea, cough, herpes zoster, nasopharyngitis, pneumonia, upper respiratory tract infection, lymphopenia, and weight loss.

Dr Lonial reported last year that adding elotuzumab to the standard therapy did not significantly increase adverse events. Overall, the drug was well tolerated and did not cause a deterioration of quality of life or exacerbate symptom burden, he added.

In 2012, there were approximately 39,000 people with multiple myeloma in the European Union. With currently available treatment, 5-year survival is less than 50% in these patients.

Immunotherapy Combination for Advanced Melanoma

The EC approved the nivolumab-ipilimumab combination for advanced melanoma after having received a positive recommendation by European reviewers only last month.

The combination was approved in the United States in 2015.

The approval by the EC is based on data from the phase 3 CheckMate-067 trial, according to a company press statement.

The EC noted that an increase in progression-free survival for the combination (compared with nivolumab alone) is established only in patients with low tumor PD-L1 expression.

The double-blind CheckMate-067 trial compared the combination with ipilimumab and nivolumab monotherapies in 945 treatment-naïve patients with advanced melanoma, with or without a BRAF V600 mutation.

After a follow-up period of at least 9 months, median progression-free survival was 2.9 months for ipilimumab alone, 6.9 months for nivolumab alone, and 11.5 months for the combination, according to results first reported at the 2015 annual meeting of the American Society of Clinical Oncology.

The risk for progression or death was 58% lower with the combination than with ipilimumab alone (HR, 0.42; P < .0001), and was 45% lower with nivolumab alone than with ipilimumab alone (HR, 0.55; P < .0001).

The combination and nivolumab alone also demonstrated a higher objective response rate (58% and 44%, respectively; P < .0001) versus ipilimumab alone (19%).

Treatment-related adverse events were much more common in patients treated with the combination than with either monotherapy.

Notably, grade 3/4 adverse events occurred in 55.0% of the combination group, but in only 16.0% of the nivolumab group and 27.3% of the ipilimumab group.

Among the most common serious adverse events in the combination group were grade 3/4 diarrhea, which occurred in 9.3% of the patients, and similarly high-grade colitis, which occurred in 7.7%.

In the combination group, 36% of patients discontinued treatment because of adverse events.

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