Participants with a History of Stroke in Lovotibeglogene Autotemcel (Lovo-cel) Clinical Trials

• Published in: Blood 2024-11, Vol.144, p.3576-3576
• Main Authors: Jaroscak, Jennifer J., Kanter, Julie, Liem, Robert I., Chawla, Anjulika, Kinney, Melissa A., Lodaya, Ankit, Pan, Lin, Sheldon-Waniga, Emily, Pierciey, Francis J., Thompson, Alexis
• Format: Article
• Language: English
• ISSN: 0006-4971
• DOI: 10.1182/blood-2024-199642

Introduction: Overt ischemic stroke is a devastating complication for patients with sickle cell disease (SCD) and is considered an indication for allogeneic transplantation. Lovo-cel is a one-time gene addition therapy for patients ≥12 y with SCD and a history of vaso-occlusive events (VOEs). Lovo-cel uses autologous transplantation of hematopoietic stem and progenitor cells transduced with a functional β-globin gene. Here, we provide a post hoc analysis of participants with histories of overt or silent stroke enrolled in the phase 1/2 HGB-206 (NCT02140554) and phase 3 HGB-210 (NCT04293185) clinical trials of lovo-cel in SCD. Methods: Study designs have been previously described (Kanter, et al. Am J Hematol. 2023;98:11-22; Kanter, et al. N Engl J Med. 2022;386:617-628). This analysis included participants from HGB-206 (Groups A, B, or C) and HGB-210 with a history of overt or silent stroke. Prior to Jul 30, 2018, HGB-206 protocols allowed enrollment of participants with history of overt stroke (without moyamoya); HGB-210 excluded such participants. Overt stroke was defined as a sudden neurological change lasting >24 hr accompanied by cerebral MRI changes. Silent stroke was defined as abnormal brain MRI in the setting of normal neurologic examination without history of findings associated with overt stroke. For participants with history of overt stroke, the following were evaluated: globin response, VOEs (evaluated 6-18 mo post lovo-cel infusion), stroke recurrence, and transfusion independence post lovo-cel infusion. For participants with history of silent stroke, stroke recurrence post lovo-cel infusion was evaluated. Outcomes are reported through Feb 2024 (inclusive of the ongoing LTF-307 extension [NCT04628585]). Results: As of Feb 2024, 67 participants had received lovo-cel in HGB-206 or HGB-210. Six participants (HGB-206 Group A, n=2; HGB-206 Group C, n=4) had a history of overt stroke (age range at informed consent, 19-34 y). Age at first stroke ranged from 4-15 y; time range between first stroke and informed consent was 4-15 y. Follow-up (range) was 54.2-95.9 mo. Both participants with overt stroke history from Group A (ie, initial manufacturing process) had improvements in total hemoglobin (Hb) and some expression of HbAT87Q which remained stable, but neither achieved globin response. One Group A participant experienced 1 VOE during the evaluation period. Both participants remain stable without recurrent stroke or VOEs up to 95.5 and 95.9 mo. The 4