PB1322 - Post hoc analysis of ADAMTS13 activity and inhibitors in a phase 2/3 study in Japanese patients with iTTP treated with caplacizumab

Tuesday, June 25, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

Kazunori Imada, MD, PhD

Director
Department of Hematology, Japanese Red Cross Osaka Hospital, Osaka, Japan
Osaka, Osaka, Japan

Co-Author(s)

YM

Yoshitaka Miyakawa

Professor
Department of Hematology, Saitama Medical University Hospital, Saitama, Japan
Saitama, Saitama, Japan
SI

Satoshi Ichikawa

Assistant Professor
Department of Hematology, Tohoku University Hospital, Sendai, Japan
Sendai, Miyagi, Japan
HU

Hitoj Uchiyama

Director
Department of Hematology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan
Kyoto, Kyoto, Japan
YU

Yasunori Ueda

Director
Department of Hematology/Oncology, Kurashiki Central Hospital, Kurashiki, Japan
Kurashiki, Okayama, Japan
YH

Yasuhiro Hashimoto

Statistician
Sanofi K.K, Tokyo, Japan
Tokyo, Tokyo, Japan
MN

Masashi Nishimi

Clinical Lead
Sanofi K.K, Tokyo, Japan
Tokyo, Tokyo, Japan
MT

Masako Tsukamoto

Medical Manager
Sanofi K.K, Tokyo, Japan
Tokyo, Tokyo, Japan
MM

Masanori Matsumoto

Professor
Department of Hematology and Blood Transfusion Medicine, Nara Medical University Hospital, Kashihara, Japan
Kashihara, Nara, Japan

Background: Caplacizumab is a von Willebrand factor–directed antibody fragment indicated to treat immune-mediated thrombotic thrombocytopenic purpura (iTTP) in conjunction with therapeutic plasma exchange (TPE) and immunosuppressive therapy. Caplacizumab was approved in Japan in 2022.

Aims: Assess ADAMTS13 activity/inhibitor level changes during caplacizumab treatment in patients with iTTP.

Methods: In the Phase 2/3 study (NCT04074187), Japanese adult patients with iTTP and ≤1 prior TPE received caplacizumab with TPE for ≥30 days post-TPE and immunosuppression and were followed for 4 weeks after treatment end. All patients provided informed consent and ethics committee approval was received. Post hoc analyses included time to sustained ADAMTS13 activity, days of TPE, and rituximab use by ADAMTS13 inhibitor boosting presence (inhibitor levels decreasing but then re-elevating regardless of degree of decrease).

Results: Nineteen patients with confirmed iTTP were included (inhibitor boosting, n=9; without inhibitor boosting, n=10). Median (95% confidence interval [CI]) time to recovery of ADAMTS13 activity to ≥10%, ≥20%, and ≥60% was 14.6 (5.9–24.8), 18.5 (5.9–31.8), and 47.5 (18.5–60.9) days (Table 1). Median (range) ADAMTS13 activity level at caplacizumab treatment end was 62.0% (29.0%–101.0%). Rituximab usage, baseline ADAMTS13 inhibitor levels ≥2 BU/mL, inhibitor boosting, and initial TTP episode were associated with delayed recovery of ADAMTS13 activity. Median (range) number of TPE days was 5.0 (3–11) and 6.5 (5–20) in patients with/without inhibitor boosting. Rituximab was used in 8/9 patients with inhibitor boosting (7/8 [87.5%] after TPE completion) and 5/10 patients without inhibitor boosting (4/5 [80.0%] before TPE completion; Table 2). One patient with inhibitor boosting experienced a recurrence 2 days after discontinuing caplacizumab due to an adverse event.

Conclusion(s): Early administration of rituximab and caplacizumab in addition to TPE and immunosuppression may reduce the risk of iTTP recurrence with inhibitor boosting in patients with iTTP.
Funded by Sanofi.