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3968 Venous Thromboembolic Events in Diffuse Large B Cell Lymphoma. Incidence, Risk Factors and Outcomes

Lymphoma: Chemotherapy, excluding Pre-Clinical Models
Program: Oral and Poster Abstracts
Session: 623. Lymphoma: Chemotherapy, excluding Pre-Clinical Models: Poster III
Monday, December 7, 2015, 6:00 PM-8:00 PM
Hall A, Level 2 (Orange County Convention Center)

Sabarish Ayyappan, MD1*, Dhivya Prabhakar, MD2*, Vinita Gupta, MD3, Brenda Cooper, MD3, Hillard M. Lazarus, MD3, Marcos De Lima, MD3 and Paolo F. Caimi, MD3

1University Hospitals Case Medical Center, Cleveland, OH
2Department of Medicine, University Hospitals Case Medical Center, Cleveland, OH
3Adult Hematologic Malignancies & Stem Cell Transplant Section, Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, OH

Venous thromboembolism (VTE) is a frequent complication of hematologic malignancies, including lymphoid malignancies. VTE results in significant morbidity and mortality in lymphoma patients. There is limited information regarding the factors affecting the risk of VTE in diffuse large B cell lymphoma (DLBCL) patients treated with chemoimmunotherapy. We conducted a retrospective analysis to identify risk factors affecting the incidence of VTE and the effect of this complication on patient outcome.

Methods: We searched the hematologic malignancies database of University Hospitals Seidman Cancer Center for patients newly diagnosed with DLBCL between 2004 and 2014. Records were reviewed for baseline demographics, evidence of known risk factors for VTE, disease characteristics, treatment history and baseline laboratory values. The univariate probability of overall survival (OS) and progression free survival (PFS) was estimated using the Kaplan-Meier method. The cumulative incidence procedure was used to estimate the incidence of VTE. To identify risk factors for VTE, univariate analysis was conducted on the potential risk factors for VTE and variables with P-value .25 were selected for analysis in the multivariate logistic regression model.

Results: 204 patients diagnosed with DLBCL were included. Patient characteristics are presented in table 1. The median age at diagnosis was 66 years and 63% had advanced stage at diagnosis. After a median follow up was 27 months, 34 patients (16.6%) presented a VTE, with a 3-year cumulative incidence of 13.7% (95% CI 9.2-20.3%). The VTE was a pulmonary embolism in 12 subjects (35%) and deep venous thrombosis in 22 patients (65%). The diagnosis of VTE was done in the presence of active disease in 23 subjects (67%) and the first VTE occurred during the first line of chemotherapy in 16 patients (47% of VTE).  Risk factors identified by univariate analysis (table 2) included previous history of VTE, coronary artery disease and congestive heart failure, bulky disease, and absence of a complete response. Treatment with an anthracycline – containing regimen resulted in decreased risk of VTE. In multivariate analysis, only the presence of bulky disease, progressive disease after first line therapy and treatment with anthracyclines retained statistical significance (p = 0.05, 0.05 and 0.006, respectively).

After a median of 27 months of follow up 113 patients had presented progression after first line therapy and 72 had died. Overall, 3-year PFS was 58.6% (95% CI 51-66.2%), with lower PFS in patients experiencing VTE (3-year PFS: VTE   34.8%; no VTE 64.4%, p=0.002). 3-year OS for the whole cohort was 70.2% (95% CI 63.1-77.3%). Patients who presented VTE had a 3-year OS of 51.3% vs. 74.8% in patients without VTE (p=0.002).

DLBCL patients present a high risk of VTE, with approximately half of all VTE events occurring early in the course of the disease. We were able to identify the presence of bulky disease at diagnosis and the absence of response to first line therapy as risk factors for developing VTE. The use of anthracycline-containing regimens was protective against VTE, likely because of the increased rates of disease response. Patients with VTE had worsened outcomes, likely a result of the presence of persistent disease, although a direct effect of VTE on long-term outcomes cannot be ruled out. Our results highlight the need for a heightened awareness of the increased risk of VTE in DLBCL patients and the need for prevention strategies.

 

Table 1. Baseline patient characteristics

Median age, years (range)

66       (20-92)

Gender (%)

          Male

          Female

115     (56.3%)

89       (43.6%)

Stage

          I

          II

          III

          IV

32       (15.9%)

43       (21.4%)

41       (20.4%)

85       (42.3%)

R-IPI

          0

          1-2

          3-5

18       (8.8%)

104     (51.0%)

80       (39.2%)

 

Table 2: Risk Factors and results of univariate analysis

Risk factor

Odds Ratio

p value

Age > 65

1.179

0.661

Male gender

0.847

0.659

Prior congestive heart failure

5.69

0.009

Prior VTE

4.016

0.07

Increased creatinine

3.479

0.181

Morbid obesity

5.121

0.252

Prior malignancy

1.283

0.674

Bulky disease

2.425

0.035

Stage

          II vs. I

          III vs. I

          IV vs. I

3.742

1.343

1.906

0.058

0.703

0.338

Elevated LDH

1.329

0.450

Hemoglobin <10g/dl

0.902

0.236

Platelets < 150,000/mcl

1

0.108

Non – GCB molecular subtype

0.658

0.439

Positive FISH for t(8;14)

1.668

0.568

Anthracycline

0.383

0.050

Rituximab

5.454

0.265

Response

          PR vs. CR

          PD vs. CR

          SD vs. CR

0.843

0.986

0.850

0.863

1.013

1.550

 

 

Disclosures: No relevant conflicts of interest to declare.

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