| The following article features coverage from the 2021 American Society of Hematology Annual Meeting. Click here to read more of Cancer Therapy Advisor’s conference coverage. |
Reinfusion of chimeric antigen receptor (CAR) T-cell therapy may reduce the risk of relapse in children and young adults with B-cell acute lymphoblastic leukemia (ALL), according to research presented at the 2021 American Society of Hematology (ASH) Annual Meeting.
Though CD19 CAR T-cell therapy has produced “remarkable responses” in ALL, relapse “remains a substantial challenge,” said Regina M. Myers, MD, of Children’s Hospital of Philadelphia (CHOP) in Pennsylvania.
With this in mind, Dr Myers and colleagues evaluated the efficacy of CAR T-cell reinfusion in a retrospective study of patients with B-cell ALL. The patients were younger than 30 years of age and were treated at CHOP between 2012 and 2020.
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Patients had received investigational CTL019 on a trial, commercial tisagenlecleucel, or investigational huCART19. All patients received at least 1 reinfusion of the same CAR product. Some patients who received a huCART19 reinfusion had received a prior CAR T-cell product as well, but all patients reinfused with CTL019 or tisagenlecleucel were CAR-naïve at their initial infusion.
The final cohort included 81 patients who received reinfusion, 68 of them CAR-naïve and 13 with prior CAR exposure. Reasons for reinfusion included nonresponse to the prior infusion, new CD19+ minimal residual disease (MRD) or relapse, and signs of poor persistence 6 months after the prior infusion, which include peripheral B-cell recovery (BCR) and CD19+ hematogones in the bone marrow.
The primary endpoint was complete response (CR) at day 28.
Results
Of the 38 patients reinfused for peripheral BCR, 14 (37%) achieved a CR. At last follow-up, 5 of these patients remained in remission without further therapy, 7 had relapsed, and 2 received alternative therapy and were in remission.
Dr Myers noted that the response rate in this group increased when patients received lymphodepleting chemotherapy prior to reinfusion.
Of the 25 patients reinfused for hematogones, 19 (76%) achieved a CR. Twelve patients remained in remission without further therapy, 6 relapsed, and 1 received alternative therapy and was in remission.
Among all patients reinfused for relapse prevention, the 36-month cumulative incidence of relapse was 40% in patients who achieved a CR and 61% in nonresponders. The 36-month overall survival rate was 90% and 86%, respectively.
Of the 10 patients reinfused for relapse, 5 (50%) achieved a CR. Three of these patients ultimately relapsed (1 after transplant). Two patients remained in remission, 1 without further therapy and 1 who received a transplant.
Of the 8 patients reinfused for nonresponse, 1 was not evaluable for response. The remaining 7 patients did not respond at day 28, and all 7 died of progressive disease at a median of 105 days after reinfusion.
Clinical Implications
Dr Myers said these results suggest that CAR T-cell reinfusions can prolong B-cell aplasia in a subset of patients with short CAR persistence, and this may reduce the risk of relapse. Reinfusions can also induce remission in patients with prior relapse, but those remissions have limited durability.
Based on these results, the clinical practice at CHOP is to offer reinfusion for patients with peripheral BCR or hematogones within 6 months of the initial CAR T-cell infusion. Patients with BCR receive lymphodepleting chemotherapy.
If patients achieve a CR, another reinfusion is planned for 2-3 months later. If the patient does not respond, alternative therapy is recommended.
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Read more of Cancer Therapy Advisor’s coverage of the ASH 2021 meeting by visiting the conference page.
Reference
Myers RM, Devine K, Li Y, et al. Outcomes after reinfusion of CD19-specific chimeric antigen receptor (CAR)-modified T cells in children and young adults with relapsed/refractory B-cell acute lymphoblastic leukemia. Presented at ASH 2021; December 11-14, 2021. Abstract 474.
