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2024-05-31T07:04:34.000Z

Survival outcomes in patients with Ph+ ALL following failure with a ponatinib-based regimen

May 31, 2024
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Learning objective: After reading this article, learners will be able to cite a new clinical development in ALL.

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The standard of care for the frontline treatment of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is chemotherapy or blinatumomab plus BCR-ABL1 tyrosine kinase inhibitor (TKI). Ponatinib-based regimens have achieved promising outcomes in Ph+ ALL; however, some patients still experience relapse. The outcomes and characteristics of patients who relapse following a frontline ponatinib-based regimen is not known.1 

Here, we summarize a retrospective study published by Short et al.1  in the American Journal of Hematology investigating the outcomes of patients with Ph + ALL following the failure of a ponatinib-based regimen. 

Study methods1

  • This retrospective study included patients with Ph+ ALL who received a frontline ponatinib-based regimen and subsequently experienced a hematologic and/or extramedullary relapse.
  • Key endpoints include relapse-free survival (RFS) and overall survival (OS).

Key findings1

  • Between March 2012 and September 2023, a total of 22 patients were included in the analysis, 73% of whom were ponatinib-resistant and 27% were ponatinib-intolerant.
  • The median time from diagnosis to relapse for ponatinib-resistant and ponatinib-intolerant patients was 24.1 months and 31.4 months, respectively.
  • The type of relapses that occurred included:
    • bone marrow only (54%);
    • central nervous system (CNS) only (27%);
    • bone marrow with CNS and/or non-CNS extramedullary involvement (14%); and
    • non-CNS extramedullary only (5%).
  • Overall, 91% of patients received ≥1 subsequent therapy following ponatinib failure.
    • All patients received a TKI-based regimen in first salvage (ponatinib [40%]; dasatinib [35%]; bosutinib [20%]; and olverembatinib [5%]).
    • Alongside TKIs, patients received either chemotherapy (65%), blinatumomab (30%), inotuzumab ozogamicin (20%), and CD19-directed chimeric antigen receptor T-cell therapy (35%).
  • Following the first salvage therapy, 90% of patients achieved a second remission.
    • All patients who received blinatumomab, inotuzumab ozogamicin, and CAR T-cell therapies achieved a complete remission or complete remission with incomplete count recovery.
  • At a median follow-up of 18.6 months, the median RFS and OS for the total cohort was 14.7 months and 22.6 months, respectively.
    • The 1-year and 2-year RFS was 55% and 37%, respectively.
    • The median OS for patients who experienced relapse in the bone marrow and extramedullary-only was 15.7 months and not reached, respectively.
    • OS rates for the total cohort and by relapse are reported in Figure 1.

Figure 1. 1-and 2-year OS in the total cohort and by type of relapse*

BM, bone marrow; OS, overall survival.
*Data from Short, et al.1

 

Key learnings
  • High response rates were observed in patients experiencing relapse after salvage therapy following failure with ponatinib regimen.
  • The study was limited by a small sample size, warranting long-term follow-up analyses to confirm the optimal consolidative strategy for patients who relapsed following a ponatinib-based regimen in first line.

  1. Short N, Jabbour E, Nasr LF, et al. Characteristics and outcomes of patients with relapsed Philadelphia chromosome-positive acute lymphoblastic leukemia after failure of a frontline ponatinib-containing therapy. Am J Hematol. 2024; DOI: 1002/ajh.27329

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