674P - Response of thrombopoietin receptor agonists in MDM2 inhibitor induced thrombocytopenia

Background

MDM2 targets p53 for proteasomal degradation and has been exploited as a therapeutic target. Clinical trials have evaluated the efficacy and safety of MDM2 inhibitors (MDM2i), with thrombocytopenia being recognized as a class effect. Thrombopoietin Receptor Agonists (TPO-RAs) have been shown to improve thrombocytopenia secondary to chemotherapy, but their role in thrombocytopenia induced by MDM2 inhibition remains unclear.

Methods

Patients who were enrolled in any MDM2i clinical trial were identified from February 2014 to March 2023 at MSKCC. Patient characteristics and safety outcomes were collected from medical record. Statistical analysis consisted of the Mann-Whitney test.

Results

113 Patients treated with 4 MDM2i using 8 different dosing schedules were evaluated. The median age was 59 years (range 19-89) and patients received a median of 2 (range 0-12) prior lines of therapy. Forty eight percent of patients had liposarcoma, with the remaining 52% having other solid tumors. Thrombocytopenia of any grade were present in 50% of patients, and of these, 26% were grade 3-4. Thirteen patients who experienced grade 3-4 thrombocytopenia were evaluated for response to any TPO-RA. Among these patients, the median time to platelet recovery, defined as achieving a platelet count of 75 k/mcl or higher, was 36 days (95% CI: 11-37) in 11 patients who received a TPO-RA vs. 16 days (95% CI: 9-21) in 14 patients who did not receive a TPO-RA (p=0.085). Dose reductions occurred in approximately 45% of patients who experienced grade 3-4 thrombocytopenia, 24% of whom received a TPO-RA vs. 21% who did not receive a TPO-RA. Dose interruptions occurred in 97% of all patients who experienced grade 3-4 thrombocytopenia. Two patients in the TPO-RA cohort and one patient in the non-TPO-RA cohort never achieved a platelet count above 75 k/mcl. No reports of severe bleeding or thromboembolism were observed in the TPO-RA cohort.

Conclusions

In this retrospective study with a heterogenous patient population, no significant difference in days to resolution of grade 3-4 thrombocytopenia secondary to an MDM2i was observed in those who received TPO-RAs. The role of TPO-RAs in this setting warrants further investigation.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Raymond DeMatteo.

Funding

Has not received any funding.

Disclosure

M. Gounder: Other, Advisory Board: Rain Oncology, Karyopharm Therapeutics, Epizyme, Bayer, Springworks Therapeutics, Boehringer Ingelheim, TYME, Ayala Pharmaceuticals, Daiichi Sankyo; Other, Speaker’s Bureau: Amgen. D. Liu: Other, Advisory Board: Invitae. All other authors have declared no conflicts of interest.