医学
临床研究阶段
CD19
内科学
耐火材料(行星科学)
B细胞
慢性淋巴细胞白血病
美罗华
CD20
肿瘤科
白血病
淋巴瘤
胃肠病学
临床试验
免疫学
抗原
抗体
生物
天体生物学
作者
Claire Roddie,Eleni Tholouli,Paul Shaughnessy,Elias Jabbour,Aaron C. Logan,Katharine Hodby,Luke Mountjoy,Adrian Bloor,David Irvine,David C. Linch,Kim Orchard,William Wilson,Bilyana Popova,Juliana Dias,Giulia Agliardi,Victoria J. Spanswick,Helen L. Lowe,Marina Mitsikakou,Eftychia Charalambous,Joanna Dawes,Meera Raymond,Yanqing Hu,Wolfram Brugger,Martin Pulè,Jae H. Park,Karl S. Peggs
出处
期刊:Blood
[American Society of Hematology]
日期:2023-11-02
卷期号:142 (Supplement 1): 2114-2114
标识
DOI:10.1182/blood-2023-180666
摘要
Background: Obe-cel is an autologous CD19 chimeric antigen receptor (CAR) T cell product designed to reduce toxicity and improve persistence through a fast off-rate CD19 binding domain. The clinical activity of obe-cel has been explored in adults with R/R B-ALL in a Phase I study (ALLCAR19, NCT02935257; Roddie C et al. J Clin Oncol 2021) and a Phase Ib/II study (FELIX, NCT04404660; Roddie C et al. J Clin Oncol 2023;41[16 Suppl]:7000). Additionally, obe-cel has been tested in pts with R/R B-cell chronic lymphocytic leukemia (B-CLL) and R/R B-cell non-Hodgkin lymphoma (B-NHL) (ALLCAR19 extension; Roddie C et al. Blood 2022;140[1 Suppl]:7452-3). Pts from the ALLCAR19 and FELIX Phase Ib studies are in long-term follow up (≥22 mos), and the ALLCAR19 extension has been recruiting for 3 years. We report an analysis of long-term efficacy and safety data from the ALLCAR19 and FELIX Phase Ib studies, as well as data from the ALLCAR19 extension. Methods: ALLCAR19 is a multicenter, non-randomized, open-label Phase I study in pts aged ≥16 years with B-cell malignancies. ALLCAR19 initially recruited pts with R/R B-ALL but was then amended (extension study) to also include pts with R/R B-CLL and R/R B-NHL. FELIX is a global, single-arm Phase Ib/II study enrolling pts aged ≥18 years with R/R B-ALL.Study designs have been presented previously. Obe-cel was administered as a split dose in pts with B-ALL (target dose 410 × 10 6 CAR T cells) and pts with CLL (target dose 230 × 10 6 CAR T cells), and as a single infusion in pts with B-NHL (target dose 200 × 10 6 CAR T cells); the pt populations in the two studies were similar. Pts with B-ALL from the ALLCAR19 and FELIX Phase Ib studies are being followed long term for disease progression and survival. For this analysis, data in pts with B-ALL from the ALLCAR19 and FELIX Phase Ib studies were pooled. Data in pts with CLL or B-NHL are presented from the ALLCAR19 extension study. Results: Outcomes in pts with R/R B-ALL: Data in pts with B-ALL were pooled (20 pts from ALLCAR19 [data cut-off Jun 26, 2023] and 16 from FELIX Phase Ib [data cut-off Mar 16, 2023]). The median age of the pooled cohort was 41.5 (range 18 to 74) years and pts had received a median of 3 (range 2 to 6) prior lines of treatment. Twenty-nine of the 36 pts (81%) achieved complete remission (CR)/CR with incomplete hematologic recovery post obe-cel infusions, per investigator assessment. The event-free survival rate was 64% at 6 mos and 49% at 12 mos. With a median follow up of 43 (range 19 to 62) mos, 13/36 pts (36%) remain in remission (8 from ALLCAR19; 5 from FELIX Phase Ib). Among these 13 ongoing responders, 2 (15%) had consolidation with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Ten of the 11 ongoing responders (91%) who did not receive allo-HSCT still had detectable CAR T cells at the last follow up. All ongoing remissions were measurable residual disease negative at last available assessment. The estimated 2-, 3- and 4-year overall survival rates were 44%, 39% and 39%, respectively. Outcomes in pts with R/R B-CLL/B-NHL: The extension phase of the ALLCAR19 study enrolled 35 pts with B-CLL or B-NHL, of which 26 (B-CLL n=5; B-NHL n=21) received obe-cel (data cut-off Jun 26, 2023). The median age of this combined cohort was 61 (range 39 to 79) years and pts had received a median of 3 (range 2 to 8) prior lines of treatment. At a median follow up of 24 mos, the overall response rate for this cohort was 92% (n=24), and 58% of responders (n=14) were alive without disease progression at last follow up. Late toxicity: Of the 11 long-term R/R B-ALL responders who had not received consolidation allo-HSCT, 10 have ongoing B-cell aplasia. Of the 14 ongoing responders in the R/R B-CLL/B-NHL cohort, 12 have ongoing B-cell aplasia (<20 B cells/µl). Of note, ongoing B-cell aplasia did not correlate with an increased risk of late serious infection. No other long-term toxicity ascribed to obe-cel was reported. Conclusions: The combined analysis of data from the ALLCAR19 and FELIX Phase Ib studies shows long-term efficacy and safety of obe-cel in pts with R/R B-ALL, with approximately one-third of pts still in remission without consolidative allo-HSCT after a median follow up of >3 years. Durable responses of >2 years were also seen in pts with R/R B-CLL and R/R B-NHL.B-cell aplasia was commonly found in long-term follow up of obe-cel recipients, but without a corresponding rise in serious late infections. Obe-cel can effect durable long-term remissions in B-cell malignancies.