Incidence, onset, and management of edema and effusion in patients treated with loncastuximab tesirine for R/R DLBCL in the LOTIS clinical trial program
Alderuccio, J. P. Ardeshna, K. Hess, B. Lunning, M. Ungar, D. Burke, M. Wang, L. Q. Solh, M.
Alderuccio, J. P.
Ardeshna, K.
Hess, B.
Lunning, M.
Ungar, D.
Burke, M.
Wang, L. Q.
Solh, M.
Citations
Altmetric:
Abstract
Context: Loncastuximab tesirine (Lonca), an antibody-drug
conjugate (ADC) comprising an anti-CD19 antibody conjugated to
a pyrrolobenzodiazepine (PBD) dimer cytotoxin, is the fi rst FDA approved PBD-containing ADC. Lonca is indicated for relapsed/
refractory DLBCL after ≥2 systemic treatments. Several TEAEs,
including edema and effusions, appear to be PBD-related (Saber,
et al 2019). Objective: To further characterize edema and effusion
by assessing the time to onset, duration, and management in the
pivotal LOTIS-2 clinical trial (NCT03589469). Methods: Key
safety outcomes: median time to onset and median duration of
edema and effusion (April 6, 2020 cutoff date). Missing AE end
dates were imputed using the date of new anticancer therapy (NAT),
the end of study (EOS), or data cutoff. Partial AE end dates were
imputed using the last month or last day of the month bounded
by EOS/data cutoff (when EOS is not reached) or NAT date. All
AE start dates are complete or partial, with day imputed to the
fi rst day of the month, bounded by fi rst dose date. After AE start/
end date imputation, duration was calculated at the patient level.
Results: In LOTIS-2 (N=145), dexamethasone pre-medication was
administered to reduce the risk of PBD toxicities, based on outcomes
from the phase 1, dose-fi nding study (LOTIS-1; NCT02669017).
Edema occurred in 27.6% of patients; median time to onset was
40.0 days (range 1–277). Median duration: 50.5 days (2-407).
Grade 3 edema occurred in 3.4% of patients. Median time to onset:
106.0 days (9–183); median duration: 5.0 days (3–112).Effusions
occurred in 11.0% of patients; median time to onset was 51.5 days
(3–203). Median duration: 19.5 days (4–252). Grade 3 effusion
occurred in 2.7% of patients. Median time to onset: 118.0 days (17–
277); median duration: 20.5 days (6-82). Five patients (12.5%) with
edema and one patient (6.3%) with effusion underwent Lonca re-challenge; diuretics, primarily spironolactone, were commonly used
to manage edema and effusion. Conclusions: Edema and effusions
in LOTIS-2 were generally reversible and manageable, with dose delays or modifi cations recommended for Grade ≥2 events. Grade
≥3 edema or effusion was uncommon and typically developed later
in therapy
Description
Date
2021
Publisher
Collections
Keywords
Type
Other
Citation
Alderuccio JP, Ardeshna K, Hess B, Radford J, Lunning M, Ungar D, et al. Incidence, Onset, and Management of Edema and Effusion in Patients Treated with Loncastuximab Tesirine for R/R DLBCL in the LOTIS Clinical Trial Program. Clinical Lymphoma Myeloma & Leukemia. 2021;21:S397-S8.