Publications by authors named "Erin A Dean"

3 Publications

  • Page 1 of 1

Tumor interferon signaling and suppressive myeloid cells are associated with CAR T-cell failure in large B-cell lymphoma.

Blood 2021 May;137(19):2621-2633

Department of Blood and Marrow Transplant and Cellular Immunotherapy.

Axicabtagene ciloleucel (axi-cel) is a chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory large B-cell lymphoma (LBCL). This study evaluated whether immune dysregulation, present before CAR T-cell therapy, was associated with treatment failure. Tumor expression of interferon (IFN) signaling, high blood levels of monocytic myeloid-derived suppressor cells (M-MDSCs), and high blood interleukin-6 and ferritin levels were each associated with a lack of durable response. Similar to other cancers, we found that in LBCL tumors, IFN signaling is associated with the expression of multiple checkpoint ligands, including programmed cell death-ligand 1, and these were higher in patients who lacked durable responses to CAR-T therapy. Moreover, tumor IFN signaling and blood M-MDSCs associated with decreased axi-cel expansion. Finally, patients with high tumor burden had higher immune dysregulation with increased serum inflammatory markers and tumor IFN signaling. These data support that immune dysregulation in LBCL promotes axi-cel resistance via multiple mechanistic programs: insufficient axi-cel expansion associated with both circulating M-MDSC and tumor IFN signaling, which also gives rise to expression of immune checkpoint ligands.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood.2020007445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120145PMC
May 2021

Diffuse Intrasinusoidal Hepatic Metastasis from Breast Cancer Presenting as Liver Failure: Effective and Rapid Treatment with Weekly Low-Dose Adriamycin.

Am J Case Rep 2020 Sep 2;21:e924141. Epub 2020 Sep 2.

Department of Internal and Hospital Medicine, Moffitt Cancer Center and Research Institute, Tampa, FL, USA.

BACKGROUND Hepatic metastasis is well known in breast cancer. Approximately 12-20% of breast cancer patients will develop liver metastasis, which usually presents as discrete mass lesions. Rarely, metastatic spread can be so diffuse that it is unidentifiable on imaging but can progress to fulminant hepatic failure. Our case report suggests that clinicians need to have a high index of suspicion when patients present with rapidly decompensating liver failure in the absence of discrete radiologic hepatic lesions, and that weekly Adriamycin should be considered as a first-line therapeutic option. CASE REPORT A 28-year-old African American woman with a history of locally advanced estrogen receptor-positive, progesterone receptor-negative, and HER2-negative breast cancer presented with right upper quadrant abdominal pain and bilateral lower extremity swelling. She had been treated 3 years prior with neoadjuvant Adriamycin/cyclophosphamide - Taxol, bilateral mastectomies, radiation therapy, and tamoxifen. Diagnostic imaging revealed massive hepatomegaly and extensive areas of liver ischemia/necrosis without discrete masses or arterial/venous thrombosis. Biopsy of the liver revealed metastatic carcinoma diffusely infiltrating the hepatic sinusoids. Extensive work up for other etiologies of liver disease was negative. The patient's liver function quickly decompensated over several days. She was treated with weekly single-agent low-dose Adriamycin, and this resulted in successful reversal of her liver function tests back to baseline. CONCLUSIONS In addition to having a high index of suspicion for diffuse intrasinusoidal hepatic metastasis, physicians should consider weekly low-dose Adriamycin as a first-line therapeutic option for patients with progressive liver failure and biopsy-confirmed metastatic carcinoma diffusely infiltrating the hepatic sinusoids.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12659/AJCR.924141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7491943PMC
September 2020

High metabolic tumor volume is associated with decreased efficacy of axicabtagene ciloleucel in large B-cell lymphoma.

Blood Adv 2020 07;4(14):3268-3276

Department of Blood and Marrow Transplant and Cellular Immunotherapy, and.

High metabolic tumor volume (MTV) predicts worse outcomes in lymphoma treated with chemotherapy. However, it is unknown if this holds for patients treated with axicabtagene ciloleucel (axi-cel), an anti-CD19 targeted chimeric antigen receptor T-cell therapy. The primary objective of this retrospective study was to investigate the relationship between MTV and survival (overall survival [OS] and progression-free survival [PFS]) in patients with relapsed/refractory large B-cell lymphoma (LBCL) treated with axi-cel. Secondary objectives included finding the association of MTV with response rates and toxicity. The MTV values on baseline positron emission tomography of 96 patients were calculated via manual methodology using commercial software. Based on a median MTV cutoff value of 147.5 mL in the first cohort (n = 48), patients were divided into high and low MTV groups. Median follow-up for survivors was 24.98 months (range, 10.59-51.02 months). Patients with low MTV had significantly superior OS (hazard ratio [HR], 0.25; 95% confidence interval [CI], 0.10-0.66) and PFS (HR, 0.40; 95% CI, 0.18-0.89). Results were successfully validated in a second cohort of 48 patients with a median follow-up for survivors of 12.03 months (range, 0.89-25.74 months). Patients with low MTV were found to have superior OS (HR, 0.14; 95% CI, 0.05-0.42) and PFS (HR, 0.29; 95% CI, 0.12-0.69). In conclusion, baseline MTV is associated with OS and PFS in axi-cel recipients with LBCL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/bloodadvances.2020001900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391155PMC
July 2020