A Pooled Safety Analysis of Loncastuximab Tesirine in Relapsed or Refractory DLBCL in the LOTIS Clinical Trial Program: Incidence, Onset, and Management of Myelosuppression

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.

1. 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.
2. 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.