Current and emerging therapeutic approaches for T‐cell acute lymphoblastic leukaemia

Abstract

Summary T‐cell ALL (T‐ALL) is an aggressive malignancy of T‐cell progenitors. Although survival outcomes in T‐ALL have greatly improved over the past 50 years, relapsed and refractory cases remain extremely challenging to treat and those who cannot tolerate intensive treatment continue to have poor outcomes. Furthermore, T‐ALL has proven a more challenging immunotherapeutic target than B‐ALL. In this review we explore our expanding knowledge of the basic biology of T‐ALL and how this is paving the way for repurposing established treatments and the development of novel therapeutic approaches.

Outcomes and prognostic factors of adults with refractory or relapsed T‐cell acute lymphoblastic leukemia included in measurable residual disease‐oriented trials

“…1,2,16 FLAG-Ida is among the most used and effective rescue regimens, with 30%-40% response rates and a median OS of 6 months in responders, as observed in our series. Allogeneic HSCT is the preferred option for patients T A B L E 3…”

“…The 4‐year OS probability of 18% in our series is fully representative of this situation. The therapeutic rescue options for patients with R/R ALL are limited, and there is no agreed standard of care 1,2,16 . FLAG‐Ida is among the most used and effective rescue regimens, with 30%–40% response rates and a median OS of 6 months in responders, as observed in our series.…”

“…Several trials including kinase inhibitors, gamma‐secretase inhibitors, BCL‐2 or BCL‐x inhibitors, kinase dependent cyclin (CDK4/6) inhibitors, selective inhibitors of nuclear export, and anti‐CD38 monoclonal antibodies, among others, are ongoing. Additionally, T‐cell or NK chimeric antigen receptor (CAR) therapies targeting CD1a, CD7, CD3, and CD5 are also moving forward in T‐ALL 1,2,16 …”

“…T-cell acute lymphoblastic leukemia (T-ALL) corresponds to 20%-30% of adult patients diagnosed with ALL. 1,2 Despite differences in the biology of the disease, T-ALL patients have been historically treated with the same upfront protocols as those with Philadelphia chromosome-negative B-cell precursor ALL (B-ALL), most being derived from pediatric Berlin-Frankfurt-Münster backbone chemotherapies [3][4][5][6][7] of the HyperCVAD regimen. 8 Currently, some new drugs such as nelarabine [8][9][10][11][12] and venetoclax, 13,14 among others, are being incorporated to first-line therapy in clinical trial settings.…”

“…Additionally, T-cell or NK chimeric antigen receptor (CAR) therapies targeting CD1a, CD7, CD3, and CD5 are also moving forward in T-ALL. 1,2,16 Studies on the outcomes of adult patients with relapsed or refractory (R/R) T-ALL treated with MRD-oriented chemotherapy regimens are scarce. 6,[18][19][20] Here we report the outcomes of patients with R/R T-ALL included in two consecutive MRD-oriented trials (ALL-AR-03 and ALL-HR-11) from the Spanish PETHEMA Group.…”