Cell therapy promising for Epstein-Barr virus-driven post-HSCT lymphoproliferative disease
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More than 80% of patients who responded to therapy with tabelecleucel for Epstein-Barr virus-driven post-transplant lymphoproliferative disease remained alive 2 years after initial treatment, study results showed.
The long-term survival benefit among these patients, all of whom had disease that was relapsed or refractory to rituximab (Rituxan; Genentech, Biogen), appeared similar regardless of whether they had a complete or partial response to tabelecleucel (Atara Biotherapeutics), an investigational, non-gene-edited, allogeneic Epstein-Barr virus (EBV)-specific T-cell therapy.
Rituximab is a standard therapy for patients with EBV-driven post-transplant lymphoproliferative disease (PTLD) occurring after allogeneic hematopoietic stem cell transplantation, according to Susan E. Prockop, MD, a pediatric oncologist at Memorial Sloan Kettering Cancer Center. However, median OS for patients with relapsed or rituximab-refractory disease is 1.7 months, she added.
“The poor survival ... demonstrated an urgent unmet need in this patient population,” Prockop said during a presentation.
Tabelecleucel comprises previously untreated peripheral blood mononuclear cells from unrelated donors that are separated, cultured and expanded to produce an IV infusion of T cells that specifically target EBV-infected cells. Tabelecleucel is produced for a variety of HLA profiles and matched to the recipient based on HLA restrictions and allele profiles.
The analysis by Prockop and colleagues included 50 patients (median age, 35.9 years; range 2-74; 50% men) across three clinical trials (NCT00002663, NCT01498484 and NCT02822495) evaluating tabelecleucel for EBV-positive diseases.
All patients received tabelecleucel dosed at 2 × 106 cells/kg on days 1, 8 and 15 of a 35-day treatment cycle. They underwent radiographic assessment after their initial infusion and either proceeded to follow-up monitoring or continued treatment until they experienced unacceptable toxicity, achieved maximal response or had up to four different HLA restrictions. Those who did not respond to therapy could switch to tabelecleucel with a different HLA restriction.
Patients completed a median two (range, 1-5) treatment cycles.
The analysis showed an investigator-assessed objective response rate of 62%, with a complete response rate of 48% and partial response rate of 14%. Median time to first response was 1.1 months (range, 0.6-6.4)
Researchers then evaluated OS by best response to therapy. Median follow-up was 28.2 months (range, 1.4-88.9) for those who had a complete response and 25.3 months (range, 5.1-52.4) for those with a partial response.
Results showed 1-year OS rates of 86.7% (95% CI, 64.2-95.5) for patients with a complete response to therapy and 85.7% (95% CI, 33.4-97.9) for those with a partial response. At 2 years, the OS rate remained 85.7% (95% CI, 33.4-97.9) for those with a partial response but had decreased to 81.6% (95% CI, 57.9-92.7) among those who had an initial complete response.
“Overall survival was greater in responders vs. nonresponders but was similar across patients with either a complete response or partial response,” Prockop said.
The safety analysis showed two patients experienced a treatment-related serious adverse event. No grade 5 treatment-related adverse events occurred across the studies. Additionally, researchers reported no confirmed evidence of treatment-related neurotoxicity, cytokine release syndrome or graft-versus-host disease.
“The data reported here show that across studies, [HSCT] recipients who responded to tabelecleucel for treatment of EBV-associated PTLD that was relapsed or refractory to rituximab experienced a long-term survival benefit,” Prockop said. “Tabelecleucel may help address an urgent unmet need in this high-risk population for whom there are no approved therapies.”
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Prockop S, et al. Abstract OS5-2. Presented at: European Society for Blood and Marrow Transplantation Annual Meeting (virtual meeting); March 14-17, 2021.
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