Early Study Looks at Combining HMA with Immunotherapy-Based Regimens in MDS

A phase 2 trial exploring immunotherapy-based hypomethylating agent (HMA) combinations for patients with previously untreated myelodysplastic syndrome (MDS) showed that “there are unique cytogenic and molecular predictors of response and survival” associated with the approaches.

Ian M. Bouligny, MD, of the University of Texas MD Anderson Cancer Center, and colleagues presented their findings in a poster (Abstract 4601) at the American Society of Hematology Annual Meeting.

Their study enrolled 66 patients with previously untreated disease. Patients received azacitidine with either ipilimumab (azo-ipi; 33 patients), nivolumab (aza-nivo; 20 patients), or both (aza-ipi-nivo; 13 patients). The primary efficacy outcome was overall response defined as complete response (CR), CR with limited count recovery (CL_L), or hematologic improvement (HI).

The overall response rate was 26.7% for aza-ipi, 55% for aza-nivo, and 53.8% for aza-ipi-nivo. CR was achieved by 6.7%, 40.0%, and 23.1% of patients assigned the regimens, respectively. There was no significant difference between the treatment regimens.

There was also no difference in event-free survival (EFS) or overall survival (OS) between the regimens. Median OS was 22.7 months for aza-ipi, 14.3 months for aza-nivo, and 11.8 months for aza-ipi-nivo. However, a landmark analysis showed that aza-ipi was associated with superior OS, compared with aza-ipi, for patients with IPSS-R intermediate-risk disease (P=.049).

Among patients who went on to transplant, the OS for those who received either of the doublet regimens was 49.6 months compared with 13.7 months for those who received triplet therapy (P=.008). OS was also significantly better among patients who did not experience pneumonitis compared with those who experienced grade 2 or worse pneumonitis (22.7 vs 7.4 months; P=.025).

The researchers concluded that “the doublet combinations appeared to be well tolerated” while “the triplet combination was associated with more frequent high-grade toxicity.”

Bouligny reported no conflicts of interest.

REFERENCE:

Bouligny IM, Montalban-Bravo G, Sasaki K, et al. A phase II trial of azacitidine with ipilimumab, nivolumab, or ipilimumab and nivolumab in previously untreated myelodysplastic syndrome. Abstract #4601. Presented at the American Society of Hematology Annual Meeting; December 7-10, 2024; San Diego, California.