Novel Bispecific CD19/CD22 CAR-T Therapy Deemed Tolerable in Relapsed/Refractory ALL – Cancer Therapy Advisor

Posted: May 6, 2020 at 12:43 am

A novel,bispecific CD19/CD22 chimeric antigen receptor T-cell (CAR-T) therapy wastolerable and resulted in responses among patients with acute lymphoblasticleukemia (ALL), according to results from a phase 1 trial presented at the AmericanAssociation for Cancer Research (AACR) Virtual Annual Meeting I 2020.

Thenovel CAR-T therapy was developed with the hypothesis that dual antigen-targetingstrategies may prevent antigen negative escape, Haneen Shalabi, DO, of theNational Cancer Institute and lead author and presenter of the study, said.

Thephase 1, dose-escalation study treated 13 young patients with ALL with theCD19/CD22 CAR-T therapy at 3 different dose levels, including 3 x 105,1 x 106, and 3 x 106. The bispecific construct containedFMC63 (CD19 scFv) linked with m971 (CD22 scFv) and a 4-1 BB costimulatorydomain.

Patientsunderwent lymphodepletion with fludarabine plus cyclophosphamide prior to theirCAR-T infusion. The primary endpoints were safety and toxicity, and thesecondary endpoints were efficacy, chimeric antigen receptor (CAR) expansion,and CAR persistence.

Atbaseline, the median age was 19.6 (range, 5.4-28.5). Patients had receivedprevious treatments, including hematopoietic stem cell transplant (54%),CD19-targeted therapy (69%), prior CD19 CAR T cell therapy (38.4%),blinatumomab (61.5%), CD22-targeted therapy (38.4%), inotuzumab (30.7%), andCD22 CAR-T therapy (15.4%). Extramedullary disease was present in 46.2% ofpatients.

CAR Tcells were well tolerated and toxicities were reversible in all patients, DrShalabi said.

Cytokinerelease syndrome (CRS) developed in 46% of patients, 15.4% of which was grade 3or higher. Both patients who developed grade 3 or higher CRS had received the 1x 106 dose level of the CD19/CD22 CAR-T product and both requiredtreatment with tocilizumab. One patient developed neurotoxicity, and hadreceived the 3 x 106 dose level.

Of the12 patients evaluable for efficacy, a complete response (CR) was achieved by42% (5) of patients, including all patients who received the 1 x 106 or 3 x 106 dose levelsof the CD19/CD22 CAR-T therapy. There were 2 nonresponders.

Two patientswho received 1 x 106 CAR-T and all patients who received the 3 x 106dose level were negative for minimal residual disease (MRD), with the remainingCRs demonstrating bone marrow clearance. Four of the 5 patients who were MRDnegative were also naive to CAR-T therapy.

Of the 5patients who achieved a CR, 2 relapsed with CD19-positive/CD22-positive diseaseand 3 remained in remission at a median 7 months after CAR T cell infusion.

Severalpatients, however, who were MRD negative in the bone marrow did not achieve CRin their extramedullary disease. Dr Shalabi said that these discrepant resultsbetween marrow and extramedullary disease suggests potentially limited CAR-Ttrafficking to sites of extramedullary disease. She suggested that treatmentat higher dose levels may be needed to overcome this limitation.

CAR T-cellexpansion occurred in all patents who responded, with a median peak inperipheral blood of 7%. At day 28, there were 1.3% CAR T cells in the bonemarrow. The persistence of the CAR T cells in peripheral blood was a median of45.6 days, as measured by flow cytometry.

Dr Shalabi concluded that this early experience with bispecific CD19/CD22 CAR T cells demonstrates clinical activity with reversible CRS and limited neurotoxicity. She noted that future studies will explore a 1 x 107 dose level, intensification of lymphodepletion prior to CAR-T infusion, and consideration of the potential role of immune checkpoint inhibitors to augment CAR-T in extramedullary disease.

Read more of Cancer Therapy Advisors coverage of AACR 2020 meeting by visiting the conference page.

References

Shalabi H, Yates B, Shahani S, et al. Safety and efficacy of CD19/CD22 CAR T cells in children and young adults with relapsed/refractory ALL. Presented at: American Association for Cancer Research (AACR) Virtual Annual Meeting I 2020; April 27-28, 2020. Abstract CT051.

Read the rest here:
Novel Bispecific CD19/CD22 CAR-T Therapy Deemed Tolerable in Relapsed/Refractory ALL - Cancer Therapy Advisor

Related Post

Comments are closed.

Archives