2019년06월16일sun
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.

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
양금열 광주희망병원장, 조선대병원에 필립스 초음파기기
건양대병원, 산과 명의 김태윤 前 강서미즈메디병원장 영입
전병우 교수(삼성서울병원 호흡기내과), 미국흉부외과학회 우수 초록상
서울 관악구의사회, 의협회관 신축기금 500만원
전북대병원 치과위생사회, 병원발전후원금 500만원
이동희 식품의약품안전평가원장·김진석 식약처 기획조정관
복지부 김주영 한의약산업과장·김영호 보건산업진흥과장
장문영 교수(중앙대병원 이비인후과), 대한평형의학회 젊은 연구자상
건보공단 건강장기요양업무협력단 한성옥·통합징수실 권관중 外
양혜란 분당서울대병원 교수, 유럽소아소화기영양학회 '젊은 연구자상'
문영재 전임의(전북대병원 정형외과), 대한골대사학회 최우수 논문구연상
김태영 건국대병원 정형외과 교수, 대한골절학회 학술대회 학술상
보라매병원 이재협 진료부원장·김덕겸 기획조정실장 外
유항종 과장(원자력병원 외과) 모친상