Muhit Özcan, MD, on DLBCL: Early Results on Zilovertamab Vedotin
2023 ASCO Annual Meeting
Muhit Özcan, MD, of Turkey’s Ankara University School of Medicine, discusses phase II findings from the waveLINE-004 study. It showed that the antibody-drug conjugate zilovertamab vedotin had clinically meaningful antitumor activity in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who experienced disease progression after, or have been ineligible for, autologous stem cell transplantation and/or chimeric antigen receptor T-cell therapy (Abstract 7531).
Transcript
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
Muhit Özcan, MD:
Treatment options are limited for patients with relapsed or refractory diffuse large B-cell lymphoma who are ineligible for or who have disease progression after autologous stem cell transplant and CAR T-cell therapy. ROR1 is an oncofetal transmembrane protein that's expressed in various hematological malignancies, including diffuse large B-cell lymphomas. Zilovertamab vedotin is an antibody drug conjugate compressing an anti-ROR1 monoclonal antibody plus a cleavable linker and the anti-microtubule cytotoxin monomethyl auristatin E.
Here, we present early results from the single-arm, open label, phase-II waveLINE-004 study, which is designed to evaluate the efficacy and safe zilovertamab vedotin in patients with relapsed or refractory diffused large B-cell lymphoma who are ineligible for or who have disease progression after autologous stem cell transplant or after CAR T-cell therapy.
Patients in waveLINE-004 received zilovertamab vedotin at 2.5 milligram per kilogram intravenously every three weeks. The primary endpoint was objective response rate, and the secondary endpoint was safety and tolerability. Safety was evaluated in all patients who received at least one cycle of study treatment, and efficacy was evaluated in all patients who received at least one dose of study treatment and had at least three months of follow-up.
At the data cut-off, 40 patients had received treatment. The median age of patients was 68 years, 60% of patients had received three or more prior lines of therapy, 25% of patients had undergone prior stem cell transplant, and 28% of them had undergone prior CAR T-cell therapy. The objective response rate among the 20 patients with at least three months follow up was 30%, with two patients achieving a complete response and four patients achieving a partial response. An additional five patients had stable disease for a disease control rate of 55%, 95% confidence interval, 31.5 to 76.9%. Five patients had progressive disease and four patients could not be assessed.
When change in target lesion size was evaluated, 13 or 20 patients had any reduction from baseline, and seven patients had a reduction in target lesion size of 50% or more. Treatment-related adverse events of any grade occurred in 70% of patients, most commonly diarrhea in 23, anemia in 20, neutropenia in 18, and neutrophil count decrease in 18% of patients. Grade 3 or 4 treatment-related adverse events occurred in 40% of patients and no that's due to treatment-related adverse events occurred. One patient discontinued treatment because of grade 3 treatment-related ketoacidosis. Treatment-related peripheral neuropathy occurred in 15% of patients over grade 1 or 2. No infusion-related reactions or treatment-related tumor lysis syndrome occurred.
In summary, these earlier results from waveLINE-004 showed that zilovertamab vedotin had clinically-meaningful antitumor activity and manageable safety in patients with relapsed or refractory diffused large B-cell lymphoma who are ineligible for or who have had disease progression after autologous stem cell transplantation or after CAR T-cell therapy. These results support the continued investigation of zilovertamab vedotin in patients with relapsed or refractory diffused large B-cell lymphoma.
Related Videos
The ASCO Post Staff
Eunice S. Wang, MD, of Roswell Park Comprehensive Cancer Center, and Gregory Roloff, MD, of the University of Chicago, discuss data that are the first to demonstrate post–FDA approval efficacy and toxicity rates of brexucabtagene autoleucel in adults with relapsed or refractory B-cell acute lymphoblastic leukemia. Although the data may confirm high response rates associated with this agent, they also highlight the need for interventions to reduce associated toxicities (Abstract 7001).
The ASCO Post Staff
Aaron T. Gerds, MD, of Cleveland Clinic Taussig Cancer Institute, talks about treating the anemia many patients with myelofibrosis experience because of JAK inhibitor therapy. The ACE-536-MF-001 study showed that luspatercept improved anemia and transfusion burden in this population, with a safety profile consistent with that in previous studies (Abstract 7016).
The ASCO Post Staff
Tycel J. Phillips, MD, and Alex F. Herrera, MD, both of the City of Hope National Medical Center, discuss results from the SWOG S1826 study, which showed that nivolumab and AVD (doxorubicin, vinblastine, and dacarbazine) improved progression-free survival vs brentuximab vedotin plus AVD in patients with advanced-stage classical Hodgkin lymphoma. Longer follow-up is needed to assess overall survival and patient-reported outcomes. This trial may be a key step toward harmonizing the pediatric and adult treatment of advanced-stage disease (LBA4).
The ASCO Post Staff
Enrique Grande, MD, of The University of Texas MD Anderson Cancer Center, discusses new findings that show initial responses to induction therapy with atezolizumab plus platinum and gemcitabine did not seem to impact overall survival for patients with metastatic urothelial carcinoma. Cisplatin-treated patients appeared to derive a greater benefit with atezolizumab than did carboplatin-treated patients (Abstract 4503).
The ASCO Post Staff
Georgina V. Long, MD, PhD, of Melanoma Institute Australia and The University of Sydney, discusses new data showing that patients with resected stage IIB/C melanoma who were treated with adjuvant nivolumab had prolonged recurrence-free survival compared with placebo across all biomarker subgroups. The baseline biomarkers most predictive of prolonged recurrence-free survival with nivolumab were high interferon gamma score, high tumor mutational burden, CD8 T-cell infiltration, and low C-reactive protein (Abstract 9504).