Presenter: Debra Tesoro, RPh, BCOP, Department of Medicine, Division of Medical Oncology, Siteman Cancer Center, St Louis, MO
Co-Authors: Richard Fong, PharmD, BCOP, Department of Pharmaceutical Sciences, University of California San Francisco, San Francisco, CA; Jeremy Deni, PharmD, BCPS, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL; Juan Pablo Alderuccio, MD, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL; Brad Kahl, MD, Department of Medicine, Oncology Division, Washington University, St. Louis, MO; Weiyun Ai, MD, PhD, Department of Medicine, Hematology/Oncology, University of California San Francisco, San Francisco, CA; David Ungar, MD, ADC Therapeutics America, Murray Hill, NJ; Turk Kilavuz , MD, ADC Therapeutics America, Murray Hill, NJ; Eric Yu, PhD, ADC Therapeutics America, Murray Hill, NJ; Yajuan Qin, MD, PhD, ADC Therapeutics America, Murray Hill, NJ; Daniel Nobel, PharmD, BCOP, BCPS, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL
BACKGROUND: Loncastuximab tesirine-lpyl is an antibody–drug conjugate that includes an anti-CD19 antibody that is conjugated to the alkylating agent SG3199, a pyrrolobenzodiazepine dimer cytotoxin designed to target and kill CD19-expressing malignant B-cells. Loncastuximab tesirine is indicated by the FDA for the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after ≥2 previous systemic therapies.
OBJECTIVE: To describe the incidence, time to onset, and management of grade ≥3 myelosuppression of patients receiving loncastuximab tesirine for relapsed or refractory DLBCL in the LOTIS-1 and LOTIS-2 clinical trials.
METHOD: This pooled safety analysis included patients with relapsed or refractory DLBCL from the phase 1, dose-finding LOTIS-1 clinical trial1 and the pivotal, single-arm, phase 2 LOTIS-2 clinical trial2 (data cutoff, March 1, 2021). Loncastuximab tesirine was administered every 3 weeks. LOTIS-1 used doses ranging from 0.015 mg/kg to 0.2 mg/kg, and LOTIS-2 used the approved dose in the prescribing information (0.15 mg/kg for 2 cycles, followed by 0.075 mg/kg for subsequent cycles). Growth factors were permitted, according to ASCO guidelines. Laboratory values were monitored at least weekly for the first 2 cycles and every 3 weeks thereafter. Myelosuppression events were graded according to the Common Terminology Criteria for Adverse Events version 4.0.
RESULTS: In the pooled population of patients who received an initial dose of 0.15 mg/kg (N = 215), grade ≥3 neutropenia, thrombocytopenia, and anemia occurred in 69 (32.1%), 43 (20%), and 27 (12.6%) patients, respectively. Febrile neutropenia occurred in 7 (3.3%) patients. In most patients with grade 3/4 neutropenia, the onset occurred in the first 4 months, and in most patients with grade 3/4 thrombocytopenia or anemia, the onset occurred in the first 2 months. Dose delays were the result of grade ≥3 neutropenia, thrombocytopenia, anemia, or febrile neutropenia in 22 (10.2%), 18 (8.4%), 3 (1.4%), and 1 (0.5%) patients, respectively. Treatment discontinuation occurred because of grade ≥3 thrombocytopenia and neutropenia in 5 (2.3%) and 1 (0.5%) patients, respectively. No treatment discontinuation was associated with anemia or febrile neutropenia. Neutrophil growth factors were administered as prophylaxis to 33 (15.3%) patients and as treatment to 56 (26.0%) patients.
CONCLUSION: The incidences of grade ≥3 neutropenia, thrombocytopenia, and anemia were <35%, and the incidence of febrile neutropenia was low. Although grade 3/4 neutropenia and thrombocytopenia were among the leading causes of dose delays, the majority of myelosuppression cases were manageable with dose delays and did not require dose reductions or treatment discontinuation.
- ClinicalTrials.gov. Identifier: NCT02669017. Study of ADCT-402 in patients with relapsed or refractory B-cell lineage non Hodgkin lymphoma (B-NHL). https://clinicaltrials.gov/ct2/show/NCT02669017?term=NCT02669017&draw=2&rank=1.
- ClinicalTrials.gov. Identifier: NCT03589469. Study to evaluate the efficacy and safety of loncastuximab tesirine in patients with relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2). https://clinicaltrials.gov/ct2/show/NCT03589469?term=NCT03589469&draw=2&rank=1.