2018년08월17일fri
로그인 | 회원가입
OFF
트위터로 보내기 싸이월드 공감
기사글확대 기사글축소 기사스크랩 이메일문의 프린트하기
OS in Relapsed/Refractory B-cell acute Lymphoblastic leukemia patients receiving Inotuzumab-ozogamicin VS Standard care in Phase3 Study
Hagop M Kantarjian, Daniel J DeAngelo, Anjali S Advani, Michaela Liedtke, Wendy Stock, Nicola Goekbuget, Susan O'Brien, Giovanni Martinelli, Kongming Wang, Tao Wang, M Luisa Paccagnella, Barbara Sleight, Erik Vandendries, Matthias Stelljes
[ 2016년 06월 14일 10시 54분 ]

Background


CD22 is expressed in most (>90%) cases of B-cell acute lymphoblastic leukemia (ALL) and is an attractive target for the treatment of B-cell malignancies. Inotuzumab ozogamicin (InO), a humanized anti-CD22 antibody conjugated to calicheamicin, has demonstrated significantly superior response vs standard care (SC) in the first 218 randomized patients with relapsed/refractory (R/R) ALL in the phase 3 INO-VATE trial.


Aims


To assess overall survival (OS) and progression free survival (PFS) of adults with R/R ALL receiving InO vs SC.


Methods


In this ongoing global, 2-arm, randomized phase 3 trial (NCT01564784), patients with R/R ALL (including ~15% of patients in each arm with Philadelphia-positive ALL) due to receive salvage (S) 1 or 2 therapy were randomized to InO (starting dose 1.8 mg/m2/cycle [0.8 mg/m2 on day 1; 0.5 mg/m2 on days 8 and 15 of a 21–28 day cycle (≤6 cycles)]) or SC (either fludarabine/cytarabine [ara-C]/granulocyte colony-stimulating factor [FLAG], ara-C plus mitoxantrone, or high-dose ara-C). Study was designed with two primary endpoints: 1) OS and 2) complete remission (CR)/CR with incomplete hematologic recovery (CRi) assessed in first 218 patients randomized (results previously presented). Overall study-wise type-I error was controlled by splitting 1-sided α to 0.0125 for each endpoint. Safety was assessed in all patients who received ≥1 dose of study drug. Per protocol, the final OS analysis was to occur upon observing ~248 events; 252 events (122 with InO and 130 with SC) were observed on March 8, 2016; data as of this date are presented.


Results


The ITT analysis population included 326 patients with both arms being well balanced for baseline stratification factors. The OS hazard ratio (HR) between InO and SC was 0.77 (97.5% CI, 0.58‒1.03) with 1-sided P=0.0203 and median OS 7.7 [95% CI, 6.0‒9.2] vs 6.7 [95% CI, 4.9‒8.3] months. The second primary objective of demonstrating a statistically significant improvement in final OS with InO vs SC was not met at prespecified significance level of 0.0104. The 2-year OS rate for InO vs SC was 23% (95% CI, 16‒30%) vs 10% (95% CI, 5‒16%). It was noted, however, that the OS departed from the proportional hazards assumption. Given this, a restricted mean survival time (RMST) analysis was applied and showed: mean OS was 13.9 months for InO vs 9.9 months for SC, a difference that met statistical significance. PFS was significantly longer with InO vs SC (HR, 0.45 [97.5% CI, 0.34‒0.61]; 1-sided P<0.0001), with median PFS 5.0 [95% CI, 3.7‒5.6] vs 1.8 [95% CI, 1.5‒2.2] months. Follow-up of previously reported endpoints, including objective response, MRD-negativity, and SCT rates were all superior in the InO arm compared to the SC arm by protocol-specified criteria. Updated safety results demonstrate a tolerability and toxicity profile consistent with that reported previously.


Conclusion

Compared with SC, InO provided evidence of longer OS and significantly prolonged PFS in adult patients with R/R ALL.

대기뉴스이거나 송고가 되지 않도록 설정됨
데일리메디 dailymedi@dailymedi.com
이기자의 다른뉴스보기
무통장입금 정보입력 입금자명 입금예정일자
(입금하실 입금자명 + 입금예정일자를 입력하세요)
[관련뉴스]
- 관련뉴스가 없습니다.
트위터로 보내기 싸이월드 공감
기사글확대 기사글축소 기사스크랩 이메일문의 프린트하기
한국애브비 면역학사업부 총괄 박영신 전무
한승석 서울대병원 교수, ‘젊은 연구자상’
서울시의사회 의학상, 저술상 김은경 교수(연세의대)-개원의학술상 윤창연·변건영·박용지 원장外
메드에듀센터, 충북대병원 발전기금 100만원
의정부성모 신생아 집중치료 지역센터 전담전문의 초빙
전영수 교수(강동경희대병원 정형외과), 대한고관절학회 최우수 포스터상
인제대 의약부총장 겸 백중앙의료원장 이병두 교수·상계백병원 조용균 원장 연임
유혜영 前 대한의사협회 감사(강남구의사회) 장남
임원호 원장(서울이비인후과의원) 장남
을지대병원 유혜민 교수(내분비내과), 마르퀴즈 평생공로상
고상배 교수(서울대병원 신경과), 美신경중환자학회 이사
김주은 서울의원 원장(강북구의사회) 장녀
주영식 원장(주영식이비인후과의원 ) 모친상
가천대 길병원 1진료부원장 김동영·2진료부원장양혁준·홍보실장 심재앙外