内容紹介
Summary
Ixazomib, an oral proteasome inhibitor, has been demonstrated to significantly improve progression-free survival(PFS)in patients with relapsed and refractory multiple myeloma(RRMM). Ixazomib has recently been approved in Japan, but its effectiveness and safety have not been fully investigated in a clinical setting. We retrospectively analyzed the records of 28 patients with RRMM who were treated with ixazomib in combination with lenalidomide and dexamethasone(IRd)in our institution between June 2017 and June 2018. The median patient age was 75 years at the start of IRd therapy. In total, 46.4% of the patients had previously received more than 3 treatment lines, prior to this study. The overall response rate was 37.0%, and the median PFS was 286 days. Over a median of 5 cycles of IRd, Grade 3 to 4 leukocytopenia, thrombocytopenia, and anemia occurred in 17.9%, 14.3%, and 32.1% of the patients, respectively; these incidences were higher than in previous reports. The severity of diarrhea or rash, however, was comparable with that in other studies. Patients with an estimated glomerular filtration rate of less than 50 mL/min/1.73 m2 received a lower cumulative dose of ixazomib and lenalidomide than those with other rates. PFS did not significantly differ between the 2 groups. Although it is necessary to carefully observe IRd-treated patients for hematological toxicity, IRd therapy is effective in heavily pretreated RRMM patients. It might be reasonable to reduce the dose of ixazomib in patients with renal impairment.
要旨
イキサゾミブは再発または難治性の多発性骨髄腫(RRMM)患者の無増悪生存期間(PFS)を有意に延長する経口プロテアソーム阻害薬として本邦でも承認を得たが,本邦の実臨床での治療成績の報告は限られている。われわれは,2017年6月～2018年6月までに大阪府済生会中津病院でイキサゾミブ,レナリドミド,デキサメタゾン併用療法(IRd療法)を受けた28症例のRRMM患者について有効性と安全性を後方視的に検討した。年齢中央値は75歳で,4レジメン以上の治療歴がある患者は46.4%であった。全奏効率(ORR)は37.0%でPFSの中央値は286日であった。IRd療法は中央値で5コース施行され,Grade 3～4の白血球減少,血小板減少,貧血はそれぞれ17.9%,14.3%,32.1%と既報告より頻度が高かったが,下痢,皮疹の重症度は既報告と同程度であった。推算糸球体濾過量(eGFR)が50 mL/min/1.73 m2未満の群はそれ以上の群と比べてイキサゾミブおよびレナリドミドの平均投与量が低かった。PFSは両群間で有意な差を認めなかった。IRd療法は治療歴が多い多発性骨髄腫患者に対しても有効であるが,血液毒性には注意が必要であると考えられた。また,腎機能が低下している患者においてはイキサゾミブの減量は妥当であると思われた。
目次
Ixazomib, an oral proteasome inhibitor, has been demonstrated to significantly improve progression-free survival(PFS)in patients with relapsed and refractory multiple myeloma(RRMM). Ixazomib has recently been approved in Japan, but its effectiveness and safety have not been fully investigated in a clinical setting. We retrospectively analyzed the records of 28 patients with RRMM who were treated with ixazomib in combination with lenalidomide and dexamethasone(IRd)in our institution between June 2017 and June 2018. The median patient age was 75 years at the start of IRd therapy. In total, 46.4% of the patients had previously received more than 3 treatment lines, prior to this study. The overall response rate was 37.0%, and the median PFS was 286 days. Over a median of 5 cycles of IRd, Grade 3 to 4 leukocytopenia, thrombocytopenia, and anemia occurred in 17.9%, 14.3%, and 32.1% of the patients, respectively; these incidences were higher than in previous reports. The severity of diarrhea or rash, however, was comparable with that in other studies. Patients with an estimated glomerular filtration rate of less than 50 mL/min/1.73 m2 received a lower cumulative dose of ixazomib and lenalidomide than those with other rates. PFS did not significantly differ between the 2 groups. Although it is necessary to carefully observe IRd-treated patients for hematological toxicity, IRd therapy is effective in heavily pretreated RRMM patients. It might be reasonable to reduce the dose of ixazomib in patients with renal impairment.
要旨
イキサゾミブは再発または難治性の多発性骨髄腫(RRMM)患者の無増悪生存期間(PFS)を有意に延長する経口プロテアソーム阻害薬として本邦でも承認を得たが,本邦の実臨床での治療成績の報告は限られている。われわれは,2017年6月～2018年6月までに大阪府済生会中津病院でイキサゾミブ,レナリドミド,デキサメタゾン併用療法(IRd療法)を受けた28症例のRRMM患者について有効性と安全性を後方視的に検討した。年齢中央値は75歳で,4レジメン以上の治療歴がある患者は46.4%であった。全奏効率(ORR)は37.0%でPFSの中央値は286日であった。IRd療法は中央値で5コース施行され,Grade 3～4の白血球減少,血小板減少,貧血はそれぞれ17.9%,14.3%,32.1%と既報告より頻度が高かったが,下痢,皮疹の重症度は既報告と同程度であった。推算糸球体濾過量(eGFR)が50 mL/min/1.73 m2未満の群はそれ以上の群と比べてイキサゾミブおよびレナリドミドの平均投与量が低かった。PFSは両群間で有意な差を認めなかった。IRd療法は治療歴が多い多発性骨髄腫患者に対しても有効であるが,血液毒性には注意が必要であると考えられた。また,腎機能が低下している患者においてはイキサゾミブの減量は妥当であると思われた。