Maintenance therapy in AML: Latest updates from ASH 2023

Figure 1. MRD Response Rate in the ADVANCE-II trial*

MRD, measurable residual disease. 
*Data from van de Loosdrecht.2

MRD, measurable residual disease.
*Data from van de Loosdrecht.²

• Median RFS in all patients was 30.4 months, with an estimated 2-year RFS rate of 56%
  • MRD response was associated with an improved RFS vs no MRD response (p = 0.06)
• Median OS was not reached, with an estimated 2-year and 3-year OS of 74.9% and 64.7%, respectively
  • OS was longer in patients with an MRD response compared with patients with no MRD response (p = 0.02)
• Tumor antigen-specific T-cell responses were observed in 85% of patients
• The number of vaccine-induced responses was correlated with patients remaining in CR, OS, and MRD response (Table 1)

Table 1. Number of VIR and MRD responses in the ADVANCE-II trial*

• Imaging mass cytometry showed clear interactions between T cells (CD4 and CD8) and dendritic cells (cDC1 and cDC2) at injection site
• The frequency of dendritic cells after the last dose correlated with OS
  • The highest level of dendritic cells was observed in patients with an MRD response

Presenter’s conclusion

Vididencel vaccination in MRD positive patients in CR resulted in a long-term survival benefit, and MRD response was correlated with survival outcomes. Further studies combining vididencel with other maintenance therapies are warranted.

Oral-azacitidine

As covered in our article on updates on maintenance therapy with oral azacitidine from the 65th American Society of Hematology (ASH) Annual Meeting and Exposition, results from several recent analyses support the use of oral azacitidine maintenance therapy after intensive chemotherapy in adult patients with newly diagnosed AML.

Posttransplant maintenance therapy³

The phase I/II VBP101 trial (NCT04849910) assessed tremtelectogene empogeditemcel (trem-cel; formerly known as VOR33) as a donor allograft for patients aged 18–70 years with CD33⁺ AML who have an elevated risk of relapse and are candidates for myeloablative conditioning allo-HSCT followed by gemtuzumab ozogamicin posttransplant maintenance therapy. Trem-cel is manufactured from patient-matched donor CD34⁺ cells and modified by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (CRISPR/Cas9) gene editing to lack CD33. Following engraftment with trem-cel and recovery, patients received gemtuzumab ozogamicin maintenance therapy in a 3 + 3 dose escalation schedule from 0.5 to 2.0 mg/m² every 28 days for 4–8 cycles. The primary endpoint was primary neutrophil engraftment by Day 28.

Key findings

• At the data cut-off of December 4, 2023, eight patients had been engrafted with trem-cel
• At Day 28, all patients had full myeloid chimerism
  • Median time to neutrophil engraftment was 10 days
  • Median time to platelet recovery was 15 days (excluding one patient with immune thrombocytopenia)
• Four patients received gemtuzumab ozogamicin maintenance therapy. In the three patients with sufficient follow-up:
  • there was no significant decrease in neutrophil or platelet counts;
  • no dose-limiting toxicities were reported;
  • no increase in liver function tests above the upper limit of normal was observed, with no incidences of sinusoidal obstruction syndrome/veno-occlusive disease;
  • the dose escalation committee recommended increasing the dose to 1 mg/m²; and
  • after the first dose, mean C_max was 236 ng/ml (standard deviation [SD], 151), and mean AUC_inf (area from time of dosing extrapolated to infinity) was 10,890 Hr*ng/ml (SD, 13,958).

Presenter’s conclusion

All patients who received trem-cel demonstrated primary neutrophil engraftment. Gemtuzumab ozogamicin at 0.5 mg/m² as maintenance therapy was well tolerated, and results indicate that gemtuzumab ozogamicin-related myelosuppression was prevented.

Conclusion

Several novel maintenance strategies for both the remission and posttransplant setting were presented at the 65th ASH Annual Meeting and Exposition, with promising initial results. These novel strategies have the potential to improve the poor outcomes associated with relapse in patients with AML.