Deep phenotyping of T cell populations under long‐term treatment of tacrolimus and rapamycin in patients receiving renal transplantations by mass cytometry

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of aggressive non-Hodgkin lymphomas. Angioimmunoblastic T-cell lymphoma (AITL) is a common subtype of PTCL, and patients with AITL typically have a poor prognosis with limited treatment options. Clinical studies have demonstrated the activity of romidepsin, a structurally unique, potent, bicyclic class 1 selective histone deacetylase inhibitor, in patients with relapsed or refractory AITL. In the case presented herein, we describe a patient treated with single-agent romidepsin at first diagnosis of AITL, resulting in complete remission for over 2 years and leading to the use of maintenance dosing. The patient eventually underwent a successful autologous stem cell transplant. This case illustrates the successful use of romidepsin for the long-term treatment of a patient with AITL in a clinical setting. Maintenance dosing may be an option for patients who have an extended response to romidepsin in order to optimize outcomes and to prolong time to the next subsequent line of therapy. In our case, the patient was able to remain in complete remission for more than 1 year while receiving maintenance dosing of romidepsin.

Download Full-text

High frequency of HER2-specific immunity observed in patients (pts) with HER2+ cancers treated with margetuximab (M), an Fc-enhanced anti-HER2 monoclonal antibody (mAb).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.1030 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 1030-1030 ◽

Cited By ~ 1

Author(s):

Jeffrey L. Nordstrom ◽

John Muth ◽

Courtney L. Erskine ◽

Catherine Sanders ◽

Erik C. Yusko ◽

...

Keyword(s):

T Cell ◽

High Frequency ◽

Phase 1 ◽

Term Treatment ◽

Cell Repertoire ◽

Post Dose ◽

Specific Immunity ◽

Long Term Treatment ◽

Presentation Methods

1030 Background: Previous studies have shown that 44-71% of trastuzumab (T)-treated pts develop HER2-specific immunity (Clin Cancer Res 2007, 13:5133; Cancer Res 2016, 76:3702; Breast Cancer Res 2018, 20:52). M is an Fc-engineered mAb that shares similar HER2 binding and antiproliferative activity as T. The Fc region of M has been engineered for increased affinity to the activating FcγRIIIA (CD16A) and lower binding to the inhibitory FcγRIIB (CD32B), attributes that may enhance the mAb’s immune function, such as antigen presentation. Methods: HER2+ cancer pts who progressed on prior therapy received M (0.1-6 mg/kg QW for 3 of every 4 weeks [N = 34]; or 10-18 mg/kg Q3W [N = 32]) in phase 1 trial NCT01148849. PBMC and plasma were collected pre-dose and 50 days post-dose for 46 pts and > 4 years for 3 pts on long-term treatment. Response to HER2 or control antigens (Ag) was assessed by IFNγ ELISpot and antibody (Ab) ELISA. In 14 pts, T-cell antigen receptor (TCR) repertoire was assessed by immunosequencing. Results: Following M treatment, mean frequencies of IFNγ-producing T cells specific for intra- or extracellular fragments of HER2 increased by 2.5 to 6-fold (p < 0.0027, paired t test). Most (95%) of subjects responded to ≥2 of 6 (median = 5) HER2 Ag. Mean HER2-specific Ab concentration increased by 19-54% (p < 0.0001), with all subjects responding to ≥2 (median = 5) of the 6 Ag. A small 1.6-fold increase in IFNγ response to control CMV/EBV/Flu (but not tetanus or cyclin D1) peptides was observed; no increase in Ab response to control Ag was noted. Subsets of HER2-specific T-cell and Ab responses persisted during long-term treatment. Median TCR clonality increased by 54% (p = 0.003), with an average of 125 unique clones expanding, while overall TCR diversity remained unchanged (p = 0.19). Conclusions: Treatment of HER2+ cancer with M was associated with enhanced HER2-specific T-cell and Ab responses together with increased TCR clonality, indicative of a more focused T-cell repertoire. The high frequency of HER2-specific immunity in M-treated patients ( > 95%) is consistent with its enhanced Fc region contributing to linkage of innate and adaptive immune responses.

Download Full-text