Ivosidenib for patients with IDH1 mutated R/R AML after allo-HSCT

Targeted therapies are often a therapeutic option for patients with acute myeloid leukemia (AML) who are not eligible for intensive chemotherapy regimens or allogeneic hematopoietic stem cell transplantation (allo-HSCT), and for patients with relapsed/refractory AML (R/R AML).¹ Although ivosidenib, an IDH1 inhibitor, has shown efficacy in both newly diagnosed and R/R AML, there is limited data on ivosidenib in patients with R/R AML after allo-HSCT.¹

Recently, Caillet et al.¹ published results from the IDALLO study in Hemasphere, investigating the efficacy and safety of ivosidenib in patients with IDH1-mutated R/R AML post-allo-HSCT. We summarize the key findings below.

Study design¹

• A multicenter retrospective study that enrolled patients with IDH1-mutated AML in relapse post-allo-HSCT, between June 2018 and April 2021.
• Data was collected through the European Bone Marrow Transplantation Registry.
• Ivosidenib was administered at 500 mg, once daily as a single agent.
• The study endpoints were overall response rate (complete response and complete response with incomplete hematologic recovery), overall survival, progression-free survival, and safety.

Key findings¹

• A total of 22 patients were included in the study with a median age of 54.9 years.
• The median follow-up period was 27.4 months.
• The median time to relapse after transplant was 5.8 months.
• Results for the survival endpoints are shown in Table 1.

Table 1. Study survival endpoints for patients with R/R AML treated with ivosidenib after allo-HSCT*

Survival endpoints	N = 22
ORR, %†	40.9
CR, %	36.4
Median time to response, days	40
Median DOR, months	18.3
Median OS,  months‡
Responders	Not reached
Non-responders	3.2
Median PFS, months
Responders	Not reached
Non-responders	2
CR, complete response; CRi, CR with incomplete hematological recovery; DOR, duration of response; OS, overall survival; ORR, overall response rate; PFS, progression-free survival. *Data from Caillet, et al.1 †ORR is defined by CR + CRi. ‡Median OS in responders versus non-responders was the only statistically significant difference (p < 0.001).

• At ivosidenib initiation, 45% of patients experienced neutropenia, and 55% experienced thrombocytopenia.

• After ivosidenib initiation, 23% of patients experienced Grade 3–4 neutropenia.
• In total, 14% of patients experienced an invasive fungal infection.
• Overall, 77% of patients discontinued treatment during the follow-up period
  • No treatment discontinuations were due to toxicity.
• 36% of patients died during the follow-up period
  • The main cause of death was disease progression.

Key learnings
This retrospective study supports the efficacy and favorable safety profile of ivosidenib as a single agent therapy in R/R AML after allo-HSCT. Further investigation is required to identify which patients are most likely to respond. Several studies evaluating ivosidenib in combination with other treatments in the posttransplant setting as a maintenance therapy are ongoing.