April 07, 2021
2 min learn
Prockop S, et al. Summary OS5-2. Offered at: European Society for Blood and Marrow Transplantation Annual Assembly (digital assembly); March 14-17, 2021.
Atara Biotherapeutics funded this research. Prockop experiences a marketing consultant position with Mesoblast; analysis funding from Atara Biotherapeutics (to Memorial Sloan Kettering), Jasper Prescribed drugs and Mesoblast; and being a co-inventor on mental property owned and licensed by Memorial Sloan Kettering to Atara Biotherapeutics. Please see the summary for all different researchers’ related monetary disclosures.
Greater than 80% of sufferers who responded to remedy with tabelecleucel for Epstein-Barr virus-driven post-transplant lymphoproliferative illness remained alive 2 years after preliminary therapy, research outcomes confirmed.
The long-term survival profit amongst these sufferers, all of whom had illness that was relapsed or refractory to rituximab (Rituxan; Genentech, Biogen), appeared comparable no matter whether or not they had a whole or partial response to tabelecleucel (Atara Biotherapeutics), an investigational, non-gene-edited, allogeneic Epstein-Barr virus (EBV)-specific T-cell remedy.
Rituximab is a typical remedy for sufferers with EBV-driven post-transplant lymphoproliferative illness (PTLD) occurring after allogeneic hematopoietic stem cell transplantation, based on Susan E. Prockop, MD, a pediatric oncologist at Memorial Sloan Kettering Most cancers Middle. Nevertheless, median OS for sufferers with relapsed or rituximab-refractory illness is 1.7 months, she added.
“The poor survival … demonstrated an pressing unmet want on this affected person inhabitants,” Prockop stated throughout a presentation.
Tabelecleucel contains beforehand untreated peripheral blood mononuclear cells from unrelated donors which are separated, cultured and expanded to supply an IV infusion of T cells that particularly goal EBV-infected cells. Tabelecleucel is produced for a wide range of HLA profiles and matched to the recipient based mostly on HLA restrictions and allele profiles.
The evaluation by Prockop and colleagues included 50 sufferers (median age, 35.9 years; vary 2-74; 50% males) throughout three medical trials (NCT00002663, NCT01498484 and NCT02822495) evaluating tabelecleucel for EBV-positive ailments.
All sufferers acquired tabelecleucel dosed at 2 × 106 cells/kg on days 1, 8 and 15 of a 35-day therapy cycle. They underwent radiographic evaluation after their preliminary infusion and both proceeded to follow-up monitoring or continued therapy till they skilled unacceptable toxicity, achieved maximal response or had as much as 4 totally different HLA restrictions. Those that didn’t reply to remedy might swap to tabelecleucel with a distinct HLA restriction.
Sufferers acquired median two (vary, 1-5) therapy cycles.
The evaluation confirmed an investigator-assessed goal response price of 62%, with a whole response price of 48% and partial response price of 14%. Median time to first response was 1.1 months (vary, 0.6-6.4)
Researchers then evaluated OS by finest response to remedy. Median follow-up was 28.2 months (vary, 1.4-88.9) for many who had a whole response and 25.3 months (vary, 5.1-52.4) for these with a partial response.
Outcomes confirmed 1-year OS charges of 86.7% (95% CI, 64.2-95.5) for sufferers with a whole response to remedy and 85.7% (95% CI, 33.4-97.9) for these with a partial response. At 2 years, the OS price remained 85.7% (95% CI, 33.4-97.9) for these with a partial response however had decreased to 81.6% (95% CI, 57.9-92.7) amongst those that had an preliminary full response.
“General survival was better in responders vs. nonresponders however was comparable throughout sufferers with both a whole response or partial response,” Prockop stated.
The protection evaluation confirmed two sufferers skilled a treatment-related critical adversarial occasion. No grade 5 treatment-related adversarial occasions occurred throughout the research. Moreover, researchers reported no confirmed proof of treatment-related neurotoxicity, cytokine launch syndrome or graft-versus-host illness.
“The info reported right here present that throughout research, [HSCT] recipients who responded to tabelecleucel for therapy of EBV-associated PTLD that was relapsed or refractory to rituximab skilled a long-term survival profit,” Prockop stated. “Tabelecleucel could assist handle an pressing unmet want on this high-risk inhabitants for whom there aren’t any permitted therapies.”