Nurse investigators characterized the onset and management of edema and effusion with loncastuximab tesirine in the pivotal LOTIS-2 trial.
Edema and effusion are generally manageable with dose delays and modifications in patients receiving loncastuximab tesirine-lpyl (Zynlonta) for relapsed/refractory diffuse large B-cell lymphoma (DLBCL) in the phase 2 LOTIS 2 study (NCT03589469), according to results of a poster presentation at the 47th Annual Oncology Nursing Society Congress.1 Furthermore, the median onset time for any-grade edema and effusion was approximately 2 or 3 treatment cycles, while grade 3 or higher edema and effusion, while less common, had a median onset time of about 6 treatment cycles.
Loncastuximab tesirine is an FDA-approved antibody-drug conjugate made up of a CD19-targeted antibody coupled with a pyrrolobenzodiazepine (PBD) dimer cytotoxin, which is used to treat patients with relapsed/refractory DLBCL following 2 or more prior lines of systemic therapies.
The FDA approval was supported by findings from the multicenter, open-label, single-arm LOTIS 2 study (NCT03589469), which revealed that the agent elicited a 48.3% objective response rate (ORR) in this patient population.2 This included a 24.1% complete response rate.
Treatment-emergent adverse events (TRAEs) were reported in 99% (n = 143) of enrolled patients, and 72.4% of patients (n = 105), experienced a TRAE of grade 3 or higher. The PBD cytotoxin is believed to be related to several adverse events (AEs), including edema and effusion.3
Although occurrence was rare, these 2 symptoms were the most common TRAE to result in treatment discontinuation during the trial. Therefore, nurse investigators sought to characterize the onset and management of edema and effusion in the pivotal LOTIS-2 trial.
During the trial, 145 patients received loncastuximab tesirine every 3 weeks as a 30-minute infusion at a dose of 0.15 mg/kg for 2 cycles; 0.075 mg/kg for subsequent cycles. Prior to undergoing treatment with loncastuximab tesirine, patients were premedicated with dexamethasone to reduce the incidence and severity of PBD toxicities.
For patients who experienced grade 2 or higher edema/effusion (as defined by the Common Terminology Criteria for Adverse Events version 4.0), loncastuximab tesirine was withheld until the toxicity resolved to grade 1, and spironolactone was recommended to help manage the AE(s) in accordance with current guidelines.
In addition, diuretic support was added if a patient experienced weight gain, edema, or plural effusion. Furthermore, patients were instructed to monitor their weight gain and to inform their providers if they gained at least 2 pounds during the treatment period.
At a data cutoff of March 1, 2021, 27.6% of patients had experienced any-grade edema. The median time to onset was 40.0 days (range, 1-277) and the median AE duration was 50.5 days (range, 2-676). Additionally, 3.4% of patients experienced a grade 3 or higher edema; among these patients, the median time to onset was 106.0 months (range, 9-183), and the median duration was 5.0 days (range, 3-112).
Overall, 11.7% of patients experienced any-grade effusion. The median time to onset was 52 days (range, 3-234) and the median duration was 20.0 days (range, 4-581). In addition, 2.8% of patients experienced grade 3 or higher effusion; among these patients, the median time to onset was 118.0 days (range, 17-277) and median duration was 20.5 days (range, 6-411).
Across the entire evaluable population, dose delays, reductions, and withdrawals due to edema occurred in 4.8%, 0.7%, and 2.8% of patients, respectively. Similarly, effusion was responsible for dose delays, reductions, and withdrawals in 1.4%, 0%, and 2.8% of patients, respectively.
“Edema and effusion were generally manageable with dose delays and reductions,” lead study author Claudia Grandas, RN, BSN, CCRP, Sylvester Comprehensive Cancer Center, concluded in a presentation of the findings.
Loncastuximab tesirine is currently under investigation in combination with ibrutinib (Imbruvica) in the phase 2 LOTIS-3 trial (NCT03684694). As of December 2021, the combination demonstrated a high objective and complete response rate, as well as an acceptable safety profile in patients with advanced DLBCL.4 Additionally, the ongoing, phase 3 LOTIS 5 trial (NCT04384484) is comparing loncastuximab tesirine plus rituximab (Rituxan) with chemotherapy in the same setting.5
1. Grandas C, Hendrickson L, Alderuccio JP, Hess B, Ungar D, Solh M. Onset, duration, and management of edema and effusion in patients treated with loncastuximab tesirine for R/R DLBCL: updated results from the LOTIS-2 clinical trial. Presented at: 47th Annual ONS Congress; April 27-May 1, 2022; Anaheim, CA. Abstract P98.
2. Caimi PF, Ai W, Aldeurccio JP, et al. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2021;22(6):790-800. doi:10.1016/S1470-2045(21)00139-X
3. Saber H, Simpson N, Ricks TK, Leighton JK. An FDA oncology analysis of toxicities associated with PBD-containing antibody-drug conjugates. Regul Toxicol Pharmacol. 2019;107:104429. doi:10.1016/j.yrtph.2019.104429
4. Carlo-Stella C, Zinzani P, Janakiram M, et al. Planned interim analysis of a phase 2 study of loncastuximab tesirine plus ibrutinib in patients with advanced diffuse large B-cell lymphoma (LOTIS-3). Presented at: 63rd Annual American Society of Hematology Annual Meeting and Exposition; December 11-14, 2021. Abstract 54. Accessed December 11, 2021. https://bit.ly/3GGCalP
5. Study to evaluate loncastuximab tesirine with rituximab versus immunochemotherapy in participants with relapsed or refractory diffuse large B-cell lymphoma. Clinicaltrials.gov. Updated September 17, 2020. Accessed May 20, 2022. https://clinicaltrials.gov/ct2/show/NCT04384484.