Crisis Averted: Early Palliative Involvement in Gene Therapy for Sickle Cell Disease

Key Message : The novel field of gene therapy for sickle cell patients introduces an opportunity for early palliative involvement to potentially result in shortened hospital stays and decreased morbidity in this patient population.

Abstract:

Background: Casgevy, a cell-based gene therapy, was approved by the U.S. Food and Drug Administration (USFDA) in 2023 for the treatment of sickle cell disease in patients with recurrent vaso-occlusive pain crises (VOC). VOC is the most common reason a patient with sickle cell disease will both present to the emergency room and be hospitalized. Recurrent VOC contribute significantly to morbidity of the disease(1). The first USFDA approved medication of its kind, Casgevy utilizes CRISP/Cas9 genome editing technology to modify a sickle cell patient’s hematopoietic stem cells resulting in an increase of fetal hemoglobin and a decreased incidence of VOC. While necessary, mobilization and collection of a patient’s hematopoietic stem cells for this therapy can precipitate VOC via the mobilization agents used, apheresis itself, and other incidental triggers(2), introducing an opportunity for early palliative involvement.

Case Description: A 32-year-old female with Hemoglobin SS (HbSS) sickle cell disease with recurrent vaso-occlusive crises was deemed eligible for Casgevy gene therapy. She was admitted with plan for cell collection, and palliative was consulted on admission for possibility of precipitated VOC with use of bone marrow stimulant Mortixafortide. Hydromorphone patient controlled analgesia (PCA) was proactively initiated. Following administration of the Mortixafortide, the patient began having acute burning pain consistent with her prior crises. Ketamine was initiated in addition to the PCA, and uptitrated the following day to address increased pain during apheresis. Her pain was managed until collection was complete, and resolved quickly thereafter.

Discussion: The advent of gene editing therapies is promising for the future of sickle cell disease, and the number of patients undergoing these therapies is expected to increase. Given the multiple provoking factors for vaso-occlusive crisis during the mobilization and collection process for Casgevy, early palliative involvement and potentially preemptive utilization of PCAs for these patients may be helpful.

References: (1) Jang T, Poplawska M, Cimpeanu E, Mo G, Dutta D, Lim SH. Vaso-occlusive crisis in sickle cell disease: a vicious cycle of secondary events. J Transl Med. 2021 Sep 20;19(1):397. doi: 10.1186/s12967-021-03074-z. PMID: 34544432; PMCID: PMC8454100.

(2) Leonard A, Weiss MJ. Hematopoietic stem cell collection for sickle cell disease gene therapy. Curr Opin Hematol. 2024 May 1;31(3):104-114. doi: 10.1097/MOH.0000000000000807. Epub 2024 Feb 9. PMID: 38359264; PMCID: PMC11414477.