On Monday 11 December 2017 during an oral abstract session at the 59 thAnnual meeting American Society of Hematology(ASH), Magdalena Klanovaof the Charles University General Hospitalin Prague, Czech Republicon behalf of her colleagues, presented results from an exploratory, post-hoc analysis of the phase III GALLIUM and GOYA clinical trials in follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL).
The abstract (#727), “Low Peripheral Blood NK Cell Count Is Associated with Worse Clinical Outcome in Patients with Follicular Lymphoma (FL) and Diffuse Large B-Cell Lymphoma (DLBCL) Treated with Immunochemotherapy: Results from the Frontline Phase 3 GALLIUM and GOYA Trials,” was presented during Oral Session 622. “Lymphoma Biology—Non-Genetic Studies: Prognostic Biomarkers and Immune Mechanisms in Lymphoma”; this summary is based on data presented at this session and may supersede information in the pre-published ASH Abstract.
Introduction/Methods
- Obinutuzumab (G), an anti-CD20 monoclonal antibody has enhanced direct cell death activity and antibody-dependent cellular cytotoxicity (ADCC) compared to rituximab (R)
- NK cells are activated and attack the target cell once it’s bound by G/R; therefore, it has been suggested that low pre-treatment NK cell count (NKCC) may be associated with worse outcomes in G/R treated patients
- Baseline (BL) peripheral blood (PB) natural killer cell counts (NKCC), assessed by flow cytometry were available in 1064/1202 (88.6%) FL patients and 1287/1418 (90.8%) DLBCL patients
- Cell-of-origin (COO) was determined in 933/1418 DLBCL patients
- COO and BL NKCC were available in 857/1418 patients
- Whole transcriptome gene expression in tumor tissue from 552/1418 DLBCL patients
- 57-gene signature designed to reflect NK cell tumor infiltration was applied to RNA sequencing data from 552 patients
- Median score was used to define high/low subgroups
Results
- Kaplan–Meier methodology was used to estimate progression-free (PFS) and overall survival (OS), and a Cox regression univariate model was used to estimate corresponding hazard ratio (HR) and confidence interval (CI)
- Median (range) BL NKCCs were 220 cells/μL (0–3300) in FL and 200 cells/μL (0–1900) in DLBCL patients
- Overall, 108/1064 (10.2%) FL patients and 255/1287 (19.8%) DLBCL patients had low BL NKCC (<100 cells/μL)
- According to COO subtype, 83/485 (17.1%) germinal center B-cell-like (GCB), 37/140 (26.4%) unclassified, and 54/232 (23.3%) activated B-cell-like (ABC) DLBCL patients had low BL NKCC
- Low BL NKCC was associated with advanced disease
- Low BL NKCC was associated with shorter PFS in:
- FL (HR=1.57, 95% CI 1.10–2.25, P=0.01; 3-yr PFS 71.6% vs1%)
- DLBCL (HR 1.36, 95% CI 1.07–1.72, P=0.01; 3-yr PFS 62.8% vs0%)
- Low BL NKCC was associated with:
- Shorter OS in FL (HR 2.58, 95% CI 1.51–4.42, P=0.0003; 3-yr OS 87.6% vs3%)
- Worse OS in DLBCL patients vs. normal NKCC (HR 1.35, 95% CI 1.00–1.82, P=0.052; 3-yr OS 77.6% vs3%)
- Stronger impact of low BL NKCC on PFS in G-treated FL patients (HR 2.06, 95% CI 1.24–3.41, P<0.01) vs R-treated patients (HR 1.19, 95% CI 0.71–1.99, P=0.5)
- Less pronounced impact in GCB DLBCL subgroup (G-treated pts: HR 1.25, 95% CI 0.91–0.77, P=0.182; R-treated patients: HR 1.47, 95% CI 1.06–2.06, P=0.021)
This was the largest prospective collection of PB NK cells to date in FL and DLBCL, in which substantial numbers of patients had reduced NKCCs at BL, which was closely correlated with advanced disease. According to the study authors, univariate and MV analyses may have suggested that low PB NKCC is independently associated with shorter PFS in FL and DLBCL and shorter OS in FL. Likewise, low NK cell gene expression in tumor tissue was associated with shorter PFS in G-treated DLBCL pts.
The collective results from this exploratory analysis indicated that the quantitative measures of NK cells in PB and tumor tissue may, in fact, play a decisive role in determining the clinical outcome of non-Hodgkin lymphoma patients treated with an anti-CD20 antibody treatment.