ABL2 fusion

The fludarabine, cyclophosphamide, and alemtuzumab (FCA) LD regimen was also shown to extend host lymphocyte suppression and improve UCART22 expansion versus fludarabine and cyclophosphamide (FC) alone (Boissel N, et al...Cytokine release syndrome (CRS) occurred in 2/3 (67%) pts, with one G1 that resolved without treatment and one G2 that resolved after tocilizumab x1...Pt 3 was refractory to treatment, however this pt received bridging therapy with dasatinib for his ABL2 fusion, and on Day -1, only 47% of the leukemic cells expressed CD22 (down from 88% at screening)... As of 01 July 2023, 3 pts were enrolled into the first UCART22 P2 cohort at DL2. Pt 1 is a 17yo female with B-ALL with a hypodiploid karyotype and a germline TP53 mutation whose disease had previously failed to respond to multiagent chemotherapy, blinatumomab (blina), inotuzumab (ino), venetoclax (ven), allogeneic hematopoietic stem cell transplantation (HSCT), and autologous CD19 CAR T-cell therapy (CAR19) x2. Pt 2 is a 68yo female with Ph-negative B-ALL who relapsed with CD19-low disease after multiagent chemotherapy, ino, and blina.

These patients are predicted to be sensitive to ABL-class tyrosine kinase inhibitors, such as imatinib or dasatinib. Patients with ABL-class fusions were more likely male, EOI MRD+, and had poorer outcomes. Seventy-seven percent of patients enrolled on the Dasatinib arm did not complete prescribed therapy. While dasatinib was well tolerated, treatment failures occurred early, indicating alternate strategies are needed.

P2, N=53, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2023 --> Sep 2024

No abstract available

No abstract available

Ph-like ALL is a heterogeneous group of disorders, Overall survival was significantly different between the different genomic groups. Children with abl1 positive or CRLF2 positive had better survival, while those with PDGFRB positive or abl2 positive had a poor outcome.

P2, N=57, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2023 --> Sep 2023 | Trial primary completion date: Jun 2023 --> Jun 2022

P2, N=58, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2022 --> Jun 2023 | Trial primary completion date: Jun 2022 --> Jun 2023

P2, N=58, Active, not recruiting, National Cancer Institute (NCI) | Suspended --> Active, not recruiting

P2, N=58, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended

P2, N=58, Recruiting, National Cancer Institute (NCI) | Trial primary completion date: Jul 2021 --> Jun 2022

Children with ABL-class fusion B-cell acute lymphocytic leukaemia have poor outcomes when treated with regimens that do not contain a tyrosine-kinase inhibitor, despite the use of high-risk chemotherapy regimens and frequent HSCT upon first remission. Our findings provide a reference for evaluating the potential benefit of first-line tyrosine-kinase inhibitor treatment in patients with ABL-class fusion B-cell acute lymphocytic leukaemia.

Patients with BCR‐ABL1 received imatinib...On the basis of these results, we propose an amendment to the genetic risk classification for adult ALL wherein groups with distinct outcomes comprise: (1) very high risk: CK, HoL or JAK‐STAT abnormalities; (2) high risk: all KMT2A fusions; (3) Tyrosine kinase sensitive: BCR‐ABL1 and ABL‐class fusions; (4) low‐risk ZNF384 fusions; (5) standard risk: all other patients. The integration of these primary genetic risk factors with other risk factor such as age, white cell count and MRD into an overall risk score is a key goal of our current work.

ABL-class patients displayed a high frequency of poor prednisone response (49%) and deletions affecting IKZF1 (61%), but both lacked prognostic value among these patients...Conclusions Children with ABL-class ALL have a poor outcome with contemporary treatment without TKIs, emphasizing the need to implement TKIs. This paper provides the baseline characteristics needed to interpret the potential benefit of upfront use of TKIs in ABL-class patients.