Supplementary Figure S2 from Safety, Outcomes, and T-Cell Characteristics in Patients with Relapsed or Refractory MDS or CMML Treated with Atezolizumab in Combination with Guadecitabine

O'Connell, Casey L.; Baer, Maria R.; Ørskov, Andreas Due; Saini, Sunil Kumar; Duong, Vu H.; Kropf, Patricia; Hansen, Jakob Werner; Tsao-Wei, Denice; Jang, Hyo Sik; Emadi, Ashkan; Holmberg-Thyden, Staffan; Cowland, Jack; Brinker, Brett T.; Horwood, Kristin; Burgos, Ryan; Hostetter, Galen; Youngblood, Benjamin A.; Hadrup, Sine Reker; Issa, Jean-Pierre; Jones, Peter; Baylin, Stephen B.; Siddiqi, Imran; Grønbaek, Kirsten

doi:10.1158/1078-0432.30706133

Supplementary Figure S2 from Safety, Outcomes, and T-Cell Characteristics in Patients with Relapsed or Refractory MDS or CMML Treated with Atezolizumab in Combination with Guadecitabine

https://doi.org/10.1158/1078-0432.30706133

journal contribution

posted on 2025-11-25, 12:45 authored by Casey L. O'Connell, Maria R. Baer, Andreas Due Ørskov, Sunil Kumar Saini, Vu H. Duong, Patricia Kropf, Jakob Werner Hansen, Denice Tsao-Wei, Hyo Sik Jang, Ashkan Emadi, Staffan Holmberg-Thyden, Jack Cowland, Brett T. Brinker, Kristin Horwood, Ryan Burgos, Galen Hostetter, Benjamin A. Youngblood, Sine Reker Hadrup, Jean-Pierre Issa, Peter Jones, Stephen B. Baylin, Imran Siddiqi, Kirsten Grønbaek

<p>A. Gating strategy applied on PBMCs samples evaluated by flow cytometry. CD8+ T cell memory was defined based on the expression of CD45RA and CCR7 (CD197). Cell surface phenotype (PD-1, CD39, and CD69) and intracellular activation (Ki-67) markers were quantified on CD8+ effector T cell (TEFF) based on indicated gates. B, CD8+ naïve and memory T cells in long-and short-survivors quantified before and after the treatment. C, Representative flow cytometry plots showing CD8+ T cells activation in PBMC samples from a short survivor. PD-1+ Ki-67+ expression on CD8+ T cells compared before and after the treatment.</p>

Funding

Van Andel Research Institute (VARI)-Stand Up to Cancer

National Cancer Institute Cancer Center Support Grant (CCSG)

Lundbeckfonden (Lundbeck Foundation)

Kræftens Bekæmpelse (DCS)

European Research Council

National Cancer Institute (NCI)

United States Department of Health and Human Services

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DOI - Is supplement to Safety, Outcomes, and T-Cell Characteristics in Patients with Relapsed or Refractory MDS or CMML Treated with Atezolizumab in Combination with Guadecitabine

ARTICLE ABSTRACT

We hypothesized that resistance to hypomethylating agents (HMA) among patients with myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) would be overcome by combining a programmed death-ligand 1 antibody with an HMA. We conducted a Phase I/II, multicenter clinical trial for patients with MDS not achieving an International Working Group response after at least 4 cycles of an HMA (“refractory”) or progressing after a response (“relapsed”) with 3+ or higher risk MDS by the revised International Prognostic Scoring System (IPSS-R) and CMML-1 or -2. Phase I consisted of a 3+3 dose-escalation design beginning with guadecitabine at 30 mg/m2 and escalating to 60 mg/m2 Days 1 to 5 with fixed-dose atezolizumab: 840 mg intravenously Days 8 and 22 of a 28-day cycle. Primary endpoints were safety and tolerability; secondary endpoints were overall response rate (ORR) and survival. Thirty-three patients, median age 73 (range 54–85), were treated. Thirty patients had MDS and 3 had CMML, with 30% relapsed and 70% refractory. No dose-limiting toxicities were observed in Phase I. There were 3 (9%) deaths in ≤ 30 days. Five patients (16%) came off study for drug-related toxicity. Immune-related adverse events (IRAE) occurred in 12 (36%) patients (4 grade 3, 3 grade 2, and 5 grade1). ORR was 33% [95% confidence interval (CI), 19%–52%] with 2 complete remission (CR), 3 hematologic improvement, 5 marrow CR, and 1 partial remission. Median overall survival was 15.1 (95% CI, 8.5–25.3) months. Guadecitabine with atezolizumab has modest efficacy with manageable IRAEs and typical cytopenia-related safety concerns for patients with relapsed or refractory MDS and CMML.