Interleukin-2 after autologous stem cell transplantation for hematologic malignancy: a phase I/II study

Area of Science:

• Oncology
• Immunotherapy
• Hematology

Background:

• Autologous stem cell transplantation (ASCT) for hematologic malignancies has a high relapse rate.
• Minimal residual disease is a key factor contributing to post-ASCT relapses.
• Interleukin-2 (IL-2) is being investigated as a potential agent to eliminate minimal residual disease.

Purpose of the Study:

• To identify a safe and tolerable regimen of IL-2 for administration early after ASCT.
• To establish the maximum tolerated dose (MTD) of induction IL-2.
• To evaluate the feasibility and preliminary efficacy of the identified IL-2 regimen.

Main Methods:

• Phase I/II clinical trial design.
• Escalating doses of induction IL-2 (9-12 x 10^6 IU/m²/day) followed by maintenance IL-2 (1.6 x 10^6 IU/m²/day).
• Continuous intravenous infusion (CIV) for IL-2 administration.

Main Results:

• The MTD for induction IL-2 was determined to be 9 x 10^6 IU/m²/day for 4 days.
• Eighty percent of patients completed induction IL-2; maintenance IL-2 was well tolerated.
• Significant side effects, including capillary leak, were observed in some patients; two treatment-related deaths occurred (CMV pneumonia, ARDS).

Conclusions:

• A tolerable IL-2 regimen was identified for early post-ASCT use.
• Preliminary response rates were observed in patients with non-Hodgkin lymphoma, Hodgkin disease, AML, ALL, and MM.
• Phase III trials are ongoing to confirm if this IL-2 regimen reduces relapse rates after ASCT for AML and NHL.