再発多発性骨髄腫に対する新たな免疫療法の選択肢 (Abstract 8508)

ELOQUENT-2:Elotuzumabを追加することにより再発多発性骨髄腫進行のリスクが有意に低下する
ELOQUENT-2: Adding elotuzumab significantly reduces risk of progression for relapsed multiple myeloma
第51回American Society of Clinical Oncology年次集会で発表された第III相試験の中間結果により、革新的な免疫療法が再発多発性骨髄腫の新たな治療選択肢になる可能性のあることが示唆された。このスタディにおいて、再発多発性骨髄腫の患者646人がレナリドミドとデキサメタゾン(コントロール群)またはレナリドミドとデキサメタゾンに加えelotuzumabを投与する群にランダムに割り付けられた。追跡期間中央値24か月後に、elotuzumabはがん進行および死亡のリスクを30%低下させた。Elotuzumab群患者の疾患無増悪期間(平均19.4か月)はコントロール群(平均14.9か月)よりも有意に長かった。さらに、高リスク所見―del(17p)およびt[4;14]と呼ばれる遺伝子異常―を有する二つのサブグループは、平均リスク患者と同等にelotuzumabの恩恵を被るようであった。これらのハイリスク患者においては従来の治療法は有効性が低い傾向にある。概して、elotuzumabの忍容性は良好で、患者のQOLを低下させたり症状による負荷を増強したりすることはなかった。これは多発性骨髄腫におけるモノクローナル抗体を調査した最大のスタディであり、この疾患の治療として標的免疫療法を用いた際の有益性を示した初めての第III相試験である。
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Interim results of a phase III trial presented at the American Society of Clinical Oncology's 51st Annual Meeting suggest an innovative immune-based therapy may offer a new option for patients with relapsed multiple myeloma. The new monoclonal antibody elotuzumab, added to standard lenalidomide and dexamethasone therapy, extended the duration of remissions by about five months, on average, compared to standard treatment alone.

"It appears that, for patients with relapsed multiple myeloma who would otherwise be offered lenalidomide and dexamethasone, addition of this new targeted drug makes the outcomes even better," said lead study author Sagar Lonial, M.D., Chief Medical Officer of the Winship Cancer Institute of Emory University, and professor and executive vice chair of the Department of Hematology and Medical Oncology of Emory University School of Medicine in Atlanta, Ga. "It was particularly striking that the difference between the elotuzumab and control groups seems to get bigger over time, which really speaks to the power of this immune-based approach."

Elotuzumab attaches to a cell surface protein called SLAMF7, which is found on myeloma cells and on a type of immune cells known as natural killer (NK) cells. Scientists believe that elotuzumab mounts a two-pronged attack on cancer by targeting myeloma cells directly and by enhancing the NK cells' ability to kill myeloma cells.

Currently, there are no monoclonal antibodies approved for treatment of multiple myeloma. This is the largest study of a monoclonal antibody in multiple myeloma and the first phase III trial demonstrating benefit using a targeted immune-based approach to treating the disease.

In the study, 646 patients with recurrent multiple myeloma were randomly assigned to receive lenalidomide and dexamethasone (control group) or lenalidomide and dexamethasone with elotuzumab.

At a median follow-up period of 24 months, elotuzumab reduced the risk of cancer progression and death by 30%. Patients in the elotuzumab group experienced a significantly longer period without disease progression (19.4 months, on average) than those in the control group (14.9 months, on average). In addition, two subgroups of patients with high-risk features ─ genetic abnormalities termed del(17p) and t[4;14] ─ appeared to benefit from elotuzumab as much as patients with average risk. Conventional therapies tend to be less effective in those high-risk patients. 

Overall, elotuzumab was well tolerated and did not deteriorate patient's quality of life or exacerbate symptom burden. Mild infusion reactions occurred after the first few doses in 10% of patients in the elotuzumab arm.

Ongoing clinical trials are exploring the possibility of incorporating elotuzumab into therapies for patients with newly diagnosed multiple myeloma and testing various combinations of elotuzumab and existing treatments.

 "We've made much headway over the past decade in understanding and treating multiple myeloma, the third most common blood cancer," noted ASCO President-Elect Julie M. Vose, M.D., MBA, FASCO. "This study is an innovative approach – one that combines the precision of a targeted, immune-based therapy with traditional myeloma therapy. The results are very encouraging, giving renewed hope to patients who have relapsed."

This study was funded by Bristol-Myers Squibb and AbbVie.