TY - JOUR
T1 - No free rides
T2 - Management of toxicities of novel immunotherapies in ALL, including financial
AU - Jain, Tania
AU - Litzow, Mark R.
N1 - Funding Information:
Conflict-of-interest disclosure: T.J. declares no competing financial interests. M.R.L. has received research funding from Amgen. Off-label drug use: None disclosed.
Publisher Copyright:
© 2018 by The American Society of Hematology.
PY - 2018/11/27
Y1 - 2018/11/27
N2 - Therapeutic options for acute lymphoblastic leukemia, especially in the relapsed/ refractory setting, have expanded significantly in recent times. However, this comes at the cost of toxicities: medical as well as financial. We highlight some of the unique toxicities associated with the novel agents to apprise our readers about what to expect, how to recognize them, and how to manage these toxicities. One of the toxicities seen with inotuzumab, a CD22 antibody drug conjugate, is sinusoidal obstruction syndrome, which can be fatal in .80% of patients if associated with multiorgan failure. Blinatumomab, a monoclonal antibody targeting CD19, is associated with cytokine release syndrome (CRS) and neurotoxicity, both of which require prompt recognition and management primarily with corticosteroids. CRS and neurotoxicity are more common and more severe with chimeric antigen receptor T-cell therapy (CAR-T). The fact that CAR-T cannot be discontinued on demand adds a layer of complexity to the management of related toxicities of this therapy. Tocilizumab, an interleukin-6 receptor blocker, is used to treat severe CRS from CAR-T, whereas corticosteroids remain the mainstay for neurotoxicity management. Although effective, these drugs carry a high price tag, and we review the available data on cost-effectiveness of these agents, keeping in mind that median followup on most of these studies is limited and that long-term data on durability of response remain to be seen.
AB - Therapeutic options for acute lymphoblastic leukemia, especially in the relapsed/ refractory setting, have expanded significantly in recent times. However, this comes at the cost of toxicities: medical as well as financial. We highlight some of the unique toxicities associated with the novel agents to apprise our readers about what to expect, how to recognize them, and how to manage these toxicities. One of the toxicities seen with inotuzumab, a CD22 antibody drug conjugate, is sinusoidal obstruction syndrome, which can be fatal in .80% of patients if associated with multiorgan failure. Blinatumomab, a monoclonal antibody targeting CD19, is associated with cytokine release syndrome (CRS) and neurotoxicity, both of which require prompt recognition and management primarily with corticosteroids. CRS and neurotoxicity are more common and more severe with chimeric antigen receptor T-cell therapy (CAR-T). The fact that CAR-T cannot be discontinued on demand adds a layer of complexity to the management of related toxicities of this therapy. Tocilizumab, an interleukin-6 receptor blocker, is used to treat severe CRS from CAR-T, whereas corticosteroids remain the mainstay for neurotoxicity management. Although effective, these drugs carry a high price tag, and we review the available data on cost-effectiveness of these agents, keeping in mind that median followup on most of these studies is limited and that long-term data on durability of response remain to be seen.
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U2 - 10.1182/bloodadvances.2018020198
DO - 10.1182/bloodadvances.2018020198
M3 - Review article
C2 - 30482769
AN - SCOPUS:85057213752
SN - 2473-9529
VL - 2
SP - 3393
EP - 3403
JO - Blood Advances
JF - Blood Advances
IS - 22
ER -