ASCO Annual Meeting

ASCO Annual Meeting

Perspective from Rayne H. Rouce, MD
Source:

Zhang H, et al. Abstract 10000. Presented at: ASCO Annual Meeting (virtual meeting); June 4-8, 2021.

Disclosures: Guangzhou Bio-gene funded this study. Zhang reports no relevant financial disclosures. Please see the abstract for all other researchers’ relevant financial disclosures.
June 09, 2021
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Novel CAR-T induces response prior to HSCT in younger patients with advanced AML

Perspective from Rayne H. Rouce, MD
Source:

Zhang H, et al. Abstract 10000. Presented at: ASCO Annual Meeting (virtual meeting); June 4-8, 2021.

Disclosures: Guangzhou Bio-gene funded this study. Zhang reports no relevant financial disclosures. Please see the abstract for all other researchers’ relevant financial disclosures.
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A novel chimeric antigen receptor T-cell therapy showed clinically relevant antitumor activity in nine of 11 younger patients with relapsed or refractory acute myeloid leukemia, according to early data from a phase 1/phase 2 study.

Results of the trial — presented during the virtual ASCO Annual Meeting — may indicate a role for the CAR T-cell therapy as an effective bridging strategy before hematopoietic stem cell transplant, according to the researchers.

A novel chimeric antigen receptor T-cell therapy showed clinically relevant antitumor activity in nine of 11 younger patients with relapsed or refractory acute myeloid leukemia.
Data were derived from Zhang H, et al. Abstract 10000. Presented at: ASCO Annual Meeting (virtual meeting); June 4-8, 2021.

“Outcomes of children with acute myeloid leukemia lag behind those of children with acute lymphoblastic leukemia, with 5-year DFS varying between 33.3% and 79.5% worldwide, as reported by the CONCORD-3 study,” Hui Zhang, MD, PhD, chief physician at Guangzhou Women and Children's Hospital in China, told Healio. “For those patients with refractory and/or relapsed disease, the prognosis is dismal.”

Zhang and colleagues used two investigational, gene-edited, autologous CAR-T constructs in their study. Both constructs targeted the protein C-type lectin-like molecule-1 (CLL1) on the surface of cancer cells.

Hui Zhang, MD, PhD
Hui Zhang

“CLL1 is highly expressed on AML leukemia stem cells, the majority of AML blasts and normal myeloid cells, but not on normal hematopoietic stem cells or lymphoid cells, suggesting that CLL1 is a promising target for novel AML therapy that will not affect normal hematopoiesis and lymphocyte-directed immune function,” Zhang said, adding that several preclinical studies have demonstrated the antitumor efficacy of targeting CLL1 in humanized models.

For the current study, Zhang and colleagues enrolled 11 patients (age range, 2-16 years; n = 9 male) with relapsed or refractory AML. Eight patients received CLL1-targeted CAR T cells, whereas three patients received a bispecific CAR that also targeted the CD33 protein.

Patients received the dual-targeted CLL1/CD33 CAR T cells if they had lower expression of CLL1, Zhang told Healio. In each case, he added, the scientific team discussed the proper construct to use before proceeding to CAR T-cell therapy for AML.

Patients received a lymphodepletion chemotherapy regimen of cyclophosphamide and fludarabine, followed by a single IV infusion of 0.3 × 106/kg to 1 × 106/kg CAR T cells.

Evaluating safety in terms of treatment-related adverse events served as the study’s primary aim. Secondary objectives included measurements of treatment efficacy.

Results showed all 11 patients had mild (grade 1 or grade 2) CRS; however, no patient experienced grade 3 or higher CRS. Additionally, researchers reported no incidence of immune effector cell-associated neurotoxicity syndrome and no dose-limiting toxicities so far in the study.

All patients experienced treatment-related myelosuppression attributed to previous chemotherapy, Zhang said.

The three patients who received CLL1/CD33-directed CAR T cells had either grade 1 or grade 2 hepatoxicity that was not experienced by any patient who received CLL1-directed CAR T cells.

Ten of 11 patients responded to therapy, with eight achieving a complete response within 30 days of infusion. Six patients had minimal residual disease (MRD)-negative complete responses, whereas two had MRD-positive complete responses.

Two patients who received the CLL1/CD33-directed CAR had MRD-negative complete responses within 30 days of infusion, whereas the other patient who received the bispecific CAR-T did not respond to therapy.

All patients who had no response, partial response or an MRD-positive response to CAR T-cell therapy went on to achieve MRD-negative remission after HSCT. All but two patients — one who died of graft-versus-host disease after transplant and another with stable disease who died of a lung infection 2 months after CAR-T — maintained an ongoing response to therapy as of the data cutoff date.

“Aside from current novel targeting agents (ie, BCL-2, IDH2, FLT3 and c-Kit inhibitors, anti-CD33 antibodies), CAR-T is also a good option for [treatment of] relapsed or refractory AML,” Zhang told Healio.

How effective an option is more uncertain at this point due to the small number of patients treated so far in the study, he added.

“Meanwhile, we believe that CAR-T is currently a good [bone marrow transplant]-bridging method [that] improve[s] the efficacy of [bone marrow transplant],” Zhang said. “To make our study more convincing, we plan to carry out a multicenter trial and enroll more patients.”

References:

Allemani C, et al. Lancet. 2018;doi: 10.1016/S0140-6736(17)33326-3.
Zhang H, et al. Abstract 10000. Presented at: ASCO Annual Meeting (virtual meeting); June 4-8, 2021.