Journal of Geriatric Oncology - Volume 7/6 - Supplement 1 - November 2016

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S26 A B S T R A C T S
PD-1 and PD-L1 gene expression was examined in 35 HDs
[18<50yrs and 1750yrs] and compared to 30 CLL patients
(pts) . PD-1 was significantly upregulated in CD4+, CD8+ T
cells and CD19+ B cells (p=0.015; 0.02 and 0.01, respectively)
in the older HD group. PD-1 was also upregulated in the three
subpopulations isolated from CLL patients (p=0.001; 0.002
and <0.001 respectively) when compared to a similar HD age
group. High PD-L1 expression was correlated with increased
age in HD B cells (p=0.046) with a further increase detected in
leukemic B cells compared with the older HD group (p=0.001).
BACH2-deficient mice have increased numbers of IL4-
producing CD4+ T cells and IFN-producing CD4+ and CD8+
T cells, with BACH2 known to repress PRDM1 expression
in B and T cells. We therefore examined BACH2 and PRDM1
gene expression in the HD groups finding it was significantly
downregulated in CD4+, naïve CD4+, CD8+ T cells and CD19+
B cells from the older HD group (p=0.001; 0.005; 0.004 and
0.03). BACH2 expression was further reduced in CD4+, CD8+ T
cells and CD19+ B cells from CLL patients compared to HD of
similar age (p=0.001; <0.001 and 0.004). In contrast, PRDM1 was
significantly upregulated in CD4+ and CD8+ T cells (p=0.003;
0.001) from CLL pts but not in their leukemic B cells. Western
blot analysis demonstrated that BACH2 and Blimp1 (PRDM1)
protein expression in the T and B cell subpopulations was
significantly correlated with transcript expression.
Conclusion: These data suggest that PD-1, PD-L1, BACH2
and PRDM1 gene expression is correlated with aging and
increased immunosuppression. These effects are even more
pronounced in the leukemic B-cells from CLL pts.
Disclosure of interest: None declared
Keywords: Aging, immunosenescence, tumor suppressor
gene
O06
OFATUMUMAB AS FRONT-LINE TREATMENT FOR PATIENTS
WITH CHRONIC LYMPHOCYTIC LEUKEMIA THAT ARE
ELDERLY AND HAVE SEVERE CO-MORBIDITIES AND/OR
OTHER MALIGNANCIES
C. Vitale1 , M. Ciccone1, C. Hinojosa1, M. J. Keating1,
N. Pemmaraju1, W. G. Wierda1 , G. Borthakur1, J. A. Burger1,
A. Ferrajoli1,*
1Department of Leukemia, the University of Texas MD Anderson
Cancer Center, Houston, USA
Introduction: Chronic lymphocytic leukemia (CLL) is a
disease of the elderly, and patients frequently present with
multiple comorbidities, including other cancers. Although
common in the real-world clinical practice, these patients are
excluded from participation in clinical trials.
Objectives: We designed a phase II study to investigate the
activity and toxicity of ofatumumab, a fully human type I anti-
CD20 monoclonal antibody, in elderly, unfit patients with CLL.
Methods: This clinical study included patients with
treatment-naïve CLL, age 65 years, indication for treatment
according to 2008 IWCLL guidelines, ECOG performance status
of 2-3 and/or Charlson comorbidity index 2. Patients having
another malignancy or other coexisting serious medical
conditions were allowed to enroll in this trial. Ofatumumab
was administered intravenously weekly for the first month
(300 mg on day 1 and 2,000 mg on days 8, 15, 22), then monthly
(2,000 mg on day 1) for a total of 12 months.The first 8 patients
received ofatumumab at 1,000 mg instead of 2,000 mg, but the
trial was later amended based on reports of increased efficacy
with the 2,000 mg dose.
Results: Thirty-four patients were enrolled. Median age
was 73 years (range 65-87). At baseline, 18/34 (53%) patients
had advanced stage disease. CLL risk profile assessment
showed that 59% of the patients had unmutated IGHV, 59%
were CD38 positive, 66% were ZAP70 positive, and 29% had
del(11q) and/or del(17p). Ten patients (29%) had at least one
other cancer diagnosis.
All 34 patients are evaluable for toxicity and survival.
Thirty-two patients are evaluable for response, the
remaining 2 patients discontinued treatment during the
first month, one due to the development of hemophagocytic
lymphohistiocytosis (HLH) and the other because of a grade
(G)2 allergic reaction. Twenty-four patients achieved a
response, for an overall response rate of 75%. We observed
complete responses in 6 patients (19%), including 3 patients
with negative minimal residual disease, and partial responses
in 18 patients (56%). At a median follow up of 23 months
(range 3-51 months), 20 patients (59%) remain progression-
free. Thirty-two (94%) patients are alive: one patient died
of infection two years after receiving ofatumumab and one
patient died of complications of HLH.
Infusion-related reactions were the most common
treatment-related adverse events (AEs), G1-2 in 17 patients
(50%), and G3 in 1 patient (3%). Fifteen patients (44%)
experienced G1-2 infectious AEs while one patient had
G3 infection. No G4 infections were observed. Additional
G3-4 AEs considered to be at least possibly related to the
study drug were: diarrhea/nausea/vomiting (G3; 2 patients),
hyperglycemia (G3; 1 patient), pulmonary embolism (G3; 1
patient).
Conclusion: Our experience indicates that single agent
ofatumumab is a feasible and well tolerated therapeutic
approach for treatment-naïve elderly patients with CLL. This
treatment was able to obtain durable clinical response in 75%
of the patients and was safely administered to patients with
severe comorbidities and other cancer diagnoses.
This study was funded by the National Comprehensive
Cancer Network (NCCN) Oncology Research Program.
Disclosure of interest: None declared
Keywords: Chronic lymphocytic leukemia, comorbidities,
ofatumumab