抗体製剤はALLに対し有効である（Abstract No. 6507）

Phase IIスタディにおいて難治性または再発性急性リンパ性白血病に対して61%の奏効率が認められた
Phase II study shows 61 percent response rate for patients with resistant or recurrent acute lymphoblastic leukemia
急性リンパ性白血病（ALL）細胞を選択的に破壊する化学療法薬となりうる薬剤と結合した抗体が、46人の患者の61%において疾患を根絶または著明に軽減させたとのPhase IIスタディの結果が2011年ASCOで発表された。CMC-544としても知られるこの薬剤は、90%以上のALL細胞の表面に認められた蛋白CD22を標的とする抗体および細胞毒性薬あるcalicheamicinと結合する。この薬剤がひとたびCD22に結合すると、ALL細胞はこれを内部に引き込み死滅する。今回のトライアルに組み入れられたのは、他の治療に抵抗性であるかまたは再発したALL患者であった。奏効性を評価された46人中9人が完全寛解し、14人は血小板数が完全に回復はしないが完全寛解し、5人は血球数の回復は認めないが骨髄中の芽球が5%未満となった。奏効が得られた患者のうち16人はその後、ドナーによる造血幹細胞移植を受けた。筆者らは、他の化学療法薬との併用に加え3週ごとの投与から毎週投与への移行に関して調査すべきであると提案している。
Full Text

An antibody packaged with a potent chemotherapy drug to selectively destroy acute lymphoblastic leukemia (ALL) cells eradicated or greatly reduced the disease for 61 percent of 46 patients in a phase II study. It was presented at the 47th annual meeting of the American Society of Clinical Oncology.

Patients enrolled in the trial led by investigators at The University of Texas MD Anderson Cancer Center had ALL that resisted other therapies or recurred after treatment.

"A response rate of more than 50 percent in this patient population probably makes inotuzumab ozogamicin the most active single-agent therapy ever for ALL," said Hagop Kantarjian, M.D., professor and chair of MD Anderson's Department of Leukemia and study senior investigator.

The drug, also known as CMC-544, links an antibody that targets CD22, a protein found on the surface of more than 90 percent of ALL cells, and the cytotoxic agent calicheamicin. Once the drug connects to CD22, the ALL cell draws it inside and dies.

Response rate for other second options is 20-30 percent

Kantarjian said second-line chemotherapy combinations used for ALL typically have a complete response rate of 20-30 percent. The monoclonal antibody-based drug developed by Pfizer, Inc., also is the first of its type for ALL.

The drug is safe, said Elias Jabbour, M.D., assistant professor in MD Anderson's Department of Leukemia, presented the study results at ASCO. Almost all side effects were of low grade (1-2) and manageable. Drug-induced fever was the most common side effect, reaching higher grades in nine of 48 patients.

Out of 46 patients evaluable for response, nine had a complete response, 14 had complete response without full recovery of platelets, and 5 had less than 5 percent blasts in their bone marrow without blood count recovery.

Sixteen responders subsequently received a donor blood stem cell transplant, Jabbour noted.

Combining inotuzumab with other chemotherapy might further improve ALL treatment, Jabbour said. MD Anderson has a phase II clinical trial under way following inotuzumab treatment with another monoclonal antibody drug, rituximab, currently used in some types of non-Hodgkin's lymphoma.

Rituximab targets the CD20 surface protein, which occurs in 50 percent of ALL cells.

In addition to combinations, the authors suggest that a shift from dosing every three weeks to weekly should be explored.

The clinical trial was funded by a grant from Pfizer.

Co-investigators with Jabbour and Kantarjian are Susan O'Brien, M.D., Deborah Thomas, M.D., Farhad Ravandi, M.D., Sergernne York, Monica Kwari, Stefan Faderl, M.D., Tapan Kadia, M.D., Guillermo Garcia-Manero, M.D., and Jorge Cortes, M.D., of MD Anderson's Department of Leukemia; Christopher Wilson and Robert Tarnai, of PPD, Inc.; and Anjali S. Advani, M.D., of the Cleveland Clinic Taussig Cancer Institute.