Rapcabtagene autoleucel exhibited promising response and safety data in relapsed or refractory B-cell acute lymphoblastic leukemia.
The next-generation CAR T-cell therapy rapcabtagene autoleucel (YTB323) displayed antitumor activity and a manageable safety profile in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), according to data from a phase 1/2 study (NCT03960840) presented at the
Data showed that at a median follow-up of 27.7 months (range, 19-50), patients with relapsed or refractory B-ALL who received rapcabtagene autoleucel across all dose levels (n = 35) achieved a 3-month best overall response rate (ORR) of 86% (95% CI, 70%-95%,) and these patients achieved a 3-month minimal residual disease (MRD)-negativity rate of 100%.
ORRs for dose level (DL1), DL2, DL3, and DL4 were 70% (95% CI, 35%-93%), 100% (95% CI, 54%-100%), 92% (95% CI, 82%-100%), and 83% (95% CI, 70%-95%), respectively. The median durations of response (DOR) for DL1, DL2, DL3, and DL4 were 5 months (95% CI, 2-not evaluable [NE]), 11 months (95%, 1-NE), NR (95% CI, 1-NE), and NR (95% CI, 1-NE). Moreover, the respective 12-month DOR rates for each DL were 0%, 42%, 51%, and 53%.
“Overall, the current data support the development of [rapcabtagene autoleucel] in [B-ALL],” lead study author Alessandro Rambaldi, MD, said during the presentation.
Rambaldi is a professor of hematology in the Department of Oncology and Hematology at the University of Milan in Italy.
The open-label, multi-center study enrolled patients who were at least 18 years of age with CD19-positive relapsed or refractory B-ALL.1,2 Patients also needed to have morphologic disease within their bone marrow and an ECOG performance status of 1 or less.1
If patients had received prior genetically engineered cellular product administration or had active central nervous system disease, they were not enrolled in the study.2
Patients in the study received rapcabtagene autoleucel intravenously at 1 of the 4 dose levels (DLs) that ranged from 2.5 to 12.5 x 106 cells.1 Between enrollment and day 1 of treatment, patients underwent lymphodepletion, rapcabtagene autoleucel manufacturing, and optional bridging chemotherapy. On day 1, rapcabtagene autoleucel infusions were administered to patients, followed by the first efficacy assessments on day 28.
The primary end point of the trial was safety, specifically dose-limiting toxicities (DLTs) and adverse effects (AEs). 3-month best overall responses (BOR), DOR, and cellular kinetics served as secondary end points.
Baseline characteristics revealed that patients had a median age of 41 years (range, 18-71) and were mostly male (57%) across all DLs. Most patients were white (63%), and all patients had ECOG performance status that was 1 or less. Nearly all patients had relapsed disease (97%), whereas fewer had primary refractory disease (3%).
Patients received a median of 2 prior lines of therapy (range, 1-10), with most having received 2 or more (91%). Prior allogeneic hematopoietic stem cell transplant, inotuzumab ozogamicin (Besponsa), blinatumomab (Blincyto), or inotuzumab ozogamicin plus blinatumomab administration occurred at rates of 66%, 37%, 46%, and 20%, respectively.
Regarding safety, patients experienced any-grade, grade 3 or higher, grade 5, and serious AEs at respective rates of 100%, 94%, 17%, and 74%. Any-grade cytokine release syndrome (CRS) was experienced by 86% of patients, including 23% who had grade 3 or higher CRS. Any-grade immune effector cell–associated neurotoxicity syndrome (ICANS) was experienced by 14% of patients, whereas 11% of patients experienced grade 3 or higher ICANS.
Neutropenia, anemia, and thrombocytopenia at any grade were experienced by all patients, whereas the cytopenias occurred at respective rates of 97%, 66%, and 89% for grades 3 or 4. Patients also experienced infections (71%) and secondary malignancies (11%). Finally, 63% of patients died; 46% were related to B-ALL, while 17% were related to other causes.
Patients who received rapcabtagene autoleucel at doses of 5 x 106 cells (DL2; n = 6) and 12.5 x 106 cells (DL4; n = 5) experienced cellular expansion and persistence levels of 139,000, 55,300, and 68,300 copies/µg DNA, which was significantly higher than those who received 2.5 x 106 cells doses (DL1; n = 10; 20,900 copies/µg DNA).
