Eculizumab Treatment Outcomes in Patients with Allogeneic Hematopoietic Cell Transplant (alloHCT)-Associated Thrombotic Microangiopathy (TA-TMA): A Retrospective Single-Center Experience

• Published in: Transplantation and cellular therapy 2024-02, Vol.30 (2), p.S136-S137
• Main Authors: Samara, Yazeed, Yao, Janny, Tsai, Ni-Chun, Mokhtari, Sally, Aldoss, Ibrahim, Ali, Haris, Sandhu, Karamjeet S., Salhotra, Amandeep, Stein, Anthony S., Arslan, Shukaib, Aribi, Ahmed, Borogovac, Azra, Malki, Monzr M. Al, Blackmon, Amanda, Otoukesh, Salman, Amanam, Idoroenyi, Artz, Andrew S., Curtin, Peter, Pourhassan, Hoda, Koller, Paul, Ball, Brian, Agrawal, Vaibhav, Spielberger, Ricardo, Becker, Pamela S., Stewart, F. Marc, Smith, Eileen, Marcucci, Guido, Forman, Stephen J., Pullarkat, Vinod, Nakamura, Ryotaro
• Format: Article
• Language: English
• ISSN: 2666-6367; 2666-6367
• DOI: 10.1016/j.jtct.2024.01.031

TA-TMA is an increasingly recognized post-HCT complication with no standard diagnosis or treatment criteria, a suspected incidence of 10-40%, and poor prognosis. Currently, there are no FDA-approved therapies for TA-TMA, but with identifying the role of complement as a terminal event in TA-TMA pathophysiology, complement blockade drugs like eculizumab have been used to treat this complication. Outcomes of the largest prospective study of eculizumab to treat TA-TMA in pediatric patients showed a complete response rate of 88% and a 1-year post-HCT survival rate of 66% (Jodele et al.). Limited data is available to guide therapy for adult patients. We identified a case series of 25 consecutive adult patients who received eculizumab for TA-TMA (per Cho et al, criteria) at our center (05/2014 - 07/2022). The median age at HCT was 52 years (range: 18-70). Acute leukemias were the most common (64%) primary diagnosis. Most patients got reduced intensity conditioning (68%), and the rest had TBI-based myeloablative conditioning. All patients got Tacrolimus (Tac) as part of graft-versus-host disease (GvHD) prophylaxis, with 71% receiving Tac/Sirolimus (Siro) -based regimens. The median time from HCT to TA-TMA onset was 5.5 months (range: 0.6-82.0). The median number of diagnostic criteria met was 6 (range: 4-8) with elevated LDH being the most common. Most patients (92%) had kidney dysfunction at diagnosis. Supratherapeutic Tac and Siro levels were seen within 4 weeks of diagnosis in 12/19 and 11/19 patients, respectively. GvHD was common (19/23) with 14 patients having acute GvHD preceding the TA-TMA. The median time to start eculizumab from diagnosis was 7 days (range: 0-548). All patients had Tac and/or Siro withdrawal, and 4 had plasma exchange pre-eculizumab therapy. Median doses of eculizumab were 6 (range: 1-39) at the median duration of 46 days (range: 1-467). Overall response rate (ORR), laboratory marker response, and organ response were achieved in 60% (n=15); 60% (n=15) and 68% (n=17) of patients, respectively; and ∼40% of patients with kidney disfunction responded to eculizumab. Overall survival (OS) and non-relapse mortality at 6 months were 48% (95% CI: 28-66) and 50% (95% CI: 33-76), respectively. The median OS from eculizumab initiation was 5.4 months (95% CI: 1.7-12.3). Development of acute GvHD (grade 2-4) prior to eculizumab was significantly associated with a lower response rate (30% vs. 90%, p=0.02). To our knowledge, our data represents the larg