ALBERT

Description: Abstract 2686 Background: DLBCL is the most commonly occurring form of non-Hodgkin lymphoma and is a highly curable disease, but one that is universally fatal if untreated or improperly treated. In a series of studies, we have reported racial disparities in the clinical presentation and the treatment outcomes for patients (pts) with DLBCL in the United States (Shenoy Cancer 2010; Flowers CEBP 2012). These studies showed that black pts with DLBCL are diagnosed at an age a decade younger than whites, are more likely to have advanced stage disease, and are less likely to survive 5 years. One explanation is that black patients in the US less often receive standard of care therapy (Flowers CEBP 2012). However, in a cohort study of 533 white and 144 black patients with DLBCL managed at Emory and University of Alabama-Birmingham (UAB) black race predicted worse overall survival (OS) even when black and white pts received the same therapy (CHOP; Hazard ratio [HR] 1.8, p 60 years of age (p=0.04), 73% had stage III/IV disease vs. 56% (p=0.03), and 77% had an LDH〉ULN vs. 51% (p=0.04). There were no significant differences between the two racial groups in terms of sex, ECOG PS, presence of B-symptoms (38% vs. 29%p=0.46), extranodal sites (50% vs. 78% ≤ 1, p=0.27), IPI risk, or treatment received (RCHOP 46% vs. 40% p=0.93). By the Hans, Natkunam, Tally, and Choi algorithms black patients more commonly presented with the poor-risk ABC/non-GCB subtype (by Choi black 64% ABC vs. white 37%; p= 0.01, Table). After controlling for clinical confounders including age, sex, stage, LDH, performance status, presence of B-symptoms, race, treatment (RCHOP vs. other), and ABC subtype, being 〉60 years of age [HR 3.1 95% CI 1.3–7.2], being black (HR 3.5 95% CI 1.5–8.2), and receiving treatment other than RCHOP (HR 12.8, 95% CI 3.2–50.6) were associated with inferior OS. Conclusions: The rate of ABC DLBCL is significantly higher in black pts compared to white pts in this university-based cohort from the Southern United States. Additional studies confirming these findings in larger populations and examining the mutations associated with these differences are underway to address biological differences intrinsic to DLBCL that may in part explain comparatively adverse features and outcomes for black pts with DLBCL. Disclosures: Flowers: Celgene, Spectrum, Millennium, Gilead, Janssen: Research Funding; Genentech/Roche (unpaid), Millennium (unpaid), Celgene: Consultancy. Bernal-Mizrachi:Empire Genomics (not related to current work): Patents & Royalties. Sinha:Celgene: Research Funding. Jaye:Millenium Pharmaceuticals (For single lecture on immunohistochemical subtyping of large B cell lymphomas): Honoraria.

Description: Abstract 1628 Introduction: Historically, relapsed DLBCL and HL has been associated with a high cure rate with salvage regimens followed by high dose chemotherapy and stem cell transplant (ASCT). However, patients (pts) who relapse early following upfront chemotherapy and pts who fail to respond to salvage have a poor overall response rate (ORR) with additional salvage regimens and a poor prognosis even when consolidated with ASCT (von Tresckow & Engert, 2011; Gisselbrecht et al., 2010). At present there is no standard therapy in the third-line setting for pts with DLBCL and HL. We designed a regimen: vinorelbine (30mg/m2) & paclitaxel (175mg/m2) given on day 1; etoposide (100mg/m2) & cisplatin (20mg/m2) given on days 2–5; and cytarabine (2000mg/m2) on days 4 and 5 (VTEPA) for treatment of lymphoma pts with 1° refractory disease or relapse following salvage. In phase 1, VTEPA was safe with a 33% ORR following 1 cycle (Lonial et al, 2006). Design and Methods: To examine the effectiveness of VTEPA, we conducted an IRB approved retrospective review of consecutive cases of relapsed/refractory DLBCL and HL identified from our database from 1999–2011. All pts had evidence of primary refractory disease or stable or progressive disease following first line salvage therapy. Responses following salvage VTEPA were retrospectively assessed using International Working Group Criteria (JCO 1999) for all pts. Responding pts proceeded to ASCT. Survival curves were constructed using the Kaplan-Meier method and compared with the log-rank test. Results: 74 pts (44 DLBCL and 30 HL) with a median age at diagnosis of 30 years (range 18–63) for HL and 49 years (range 20–68) for DLBCL were included. 67% of HL pts had primary refractory disease and 33% of pts had relapsed disease; 60% were stage III/IV at diagnosis. 75% of DLBCL pts had primary refractory disease and 25% of pts had relapsed disease; 73% stage III/IV. Pts received a median of 2 prior therapies (range 1–4). 63% pts with HL received prior salvage therapy with ifosfamide, carboplatin, and etoposide (ICE) and 13% with other regimens. 16 pts with HL received 1 cycle of VTEPA, 13 received 2 cycles and 1 pt received 3 cycles of VTEPA. 70% pts with DLBCL had received prior salvage therapy with rituximab (R) + ICE and 16% received other salvage regimens. 32 pts with DLBCL received 1 cycle of R-VTEPA and 12 pts received 2 cycles. The most common reported grade 3/4 toxicities were pancytopenia (97%), nausea/vomiting (58%), fatigue (30%), infectious complications (26%), diarrhea (24%), electrolyte imbalance (19%), and mucositis (16%). 70 pts (43 DLBCL and 27 HL) were evaluable for response. The ORR for DLBCL pts was 44% (9% CR and 35% PR) while that for HL pts was 70% (26% CR and 44% PR, p=0.04). 4 DLBCL pts had treatment related mortality. 34 pts went on to collect ≥2 × 106 CD34+ cells/kg; 3 pts had inadequate stem cell collection. In 23 pts collection was not attempted, and 14 pts collected stem cells prior to R+/−VTEPA. 37 pts (47%) went onto planned ASCT, and 4 pts underwent allogeneic transplantation. The PFS at 2 years for pts with HL was 68% vs. 49% for pts with DLBCL (p

Description: Abstract 1521 Background: Data from the United States Surveillance, Epidemiology, and End Results (SEER) registry indicate that black (B) Americans have a lower relative incidence of DLBCL than Whites (W), but a higher disease-specific mortality (Malik, ASH Annual Meeting 2009). Studies of the SEER-Medicare (Vance, ASH Annual Meeting 2007) and National Cancer Database (Flowers, ASH Annual Meeting 2009) populations revealed that B patients (pts) with DLBCL were less likely to receive rituximab with chemotherapy, however, full details on clinical and demographic parameters that may influence incidence and treatment selection were not available in either dataset. To examine these racial disparities in a setting with more detailed ascertainment of presenting features and the use of cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP) chemotherapy with or without rituximab (R), we studied the differences in presentation, socioeconomic status (SES), Family History, and treatment received by B and W patients with DLBCL at Emory University and UAB. Methods: Patients diagnosed with DLBCL at Emory University (1981-2010) and UAB (1985-2010) were identified from pathology, clinical and pharmacy records. Baseline demographic data, components of the International Prognostic Index (IPI: age, performance status (PS), lactate dehydrogenase (LDH), number of extranodal sites involved, and stage), B-symptoms, family history, insurance status, employment status, treatment and survival data were extracted. Racial differences in presentation, socio-demographic factors, and first-line treatment received were analyzed using Chi-squared statistical analysis. Results: A total of 862 (575 Emory and 287 UAB) patients with a confirmed diagnosis of DLBCL were identified. The median age of diagnosis for B pts (n=168) was significantly lower than that for W pts (n=607) [49 years (interquartile range [IQR] 36–60) vs. 57 years (IQR 46–69), p

Description: Abstract 3718 Poster Board III-654 Background The combination of bortezomib (B) with rituximab (R), cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) produces complete response in 〉80% of patients with lymphoma, but has been associated with significant neurotoxicity (Ribrag, Cancer 2009). To examine whether adding B to RCHOP with modified vincristine dosing could be well-tolerated, we performed a Bayesian phase I trial and assessed neurotoxicity with functional and electrophysiological measures. Methods Untreated patient with follicular lymphoma(n=9) and other indolent NonHodgkin Lymphomas (NHL; n=8) and indications for treatment based on the GELF criteria or FLIPI score〉3 received R 375mg/m2, cyclophosphamide 750mg/m2, doxorubicin 50mg/m2, vincristine 1.5mg on day 1, B 1.0-1.6mg/m2 days 1 and 8 and prednisone 100mg days 1-5 for 6-8 cycles. The maximum tolerated dose (MTD) was defined as the regimen at which 14days) occurs. Dose escalation used the Escalation with Overdose Control Bayesian method with upper bound (Θ=0.3). Functional Assessment of Cancer Therapy (FACT) Neurotoxicity (11-item; 4 point scale), NCI CTCAE general neurotoxicity score and electrodiagnostic studies were performed before treatment and after 4 cycles. Nerve conduction studies included recording of sensory and motor action potential from sural and peroneal nerves, with recording of SNAP and CMAP amplitudes. Electromyography was performed in distal muscles of the limbs. Results 16 patients with indolent lymphoma enrolled in phase I and have completed ≥ 4 cycles; 11/16 pts have completed therapy to date. Median age was 56 years (range 28-71). 6 pts (43%) had stage IV disease, 5 pts (29%) had LDH 〉 200; 76% of pts had IPI scores of 1/2; 24% had IPI ≥3; 13 (93%) had FLIPI ≥2. Pts received RCHOP + B at 1.0 (n=1), 1.3 (n=6), or 1.6 mg/m2 (n=9). Overall response rate was 100% with 8/11 evaluable pts (73%) achieving a CR. Gr 4 neutropenia occurred in 3 pts (21%), Gr≥3 neuropathy in 1 pt (7%). Results from electrodiagnostic testing following cycle 4 were available in 8 pts. 3 pts (37.5%) displayed motor and sensory neuropathic changes after 4 cycles of therapy. 2 pts (25%) had a reduction in peroneal CMAP amplitude 〉50% compared to baseline and 1 pts (12.5%) had a reduction in sural SNAP amplitude 〉50%. Following cycle number 4, ≥88% of pts reported Little/No neuropathy for each FACT item (Figure 1) FACT self-reporting and NCI CTCAE neurotoxicity scores did not correlate with electrodiagnostic testing, indicating the importance of multi-modal neurological assessments to clearly identify pts' neuropathy. Conclusions 1) B with RCHOP can safely be combined with vincristine at 1.5 mg with limited neurological toxicity compared to previously reported data. 2) BRCHOP has a high CR rate in indolent NHL worthy of exploring in phase 2 and phase 3 trials. Disclosures: Flowers: Amos Medical Faculty Development Program grant from the American Society of Hematology/Robert Wood Johnson Foundation: Research Funding; Millennium: Research Funding; Genentech/Biogen-Idec (unpaid): Consultancy.

Description: Abstract 1528 Background: While black patients (pts) have a lower relative incidence of Diffuse Large B cell lymphoma (DLBCL),previous studies have shown that they tend to present at a younger age, with more advanced stage disease and have inferior 2 year and 5 year relative survival rates (ASH 2007 4430a; ASH 2009 898a). These studies have been limited by small numbers of black pts and by being single institution analyses. We performed a combined retrospective analysis of DLBCL pts treated at Emory & University of Alabama at Birmingham (UAB) to examine demographic, clinical, International Prognostic Index (IPI) score, socioeconomic, and treatment variables to determine their impact on survival in black (B) and white (W) pts. Methods: Clinical, pathology, and pharmacy records were reviewed and 862 pts were identified with DLBCL who were evaluated or received treatment at Emory and UAB from 1981–2010. Baseline demographic data, components of the IPI [age, stage, performance status (PS), LDH, number of extranodal sites (ES)], family history of lymphoma, insurance & employment status, as well as treatment and survival data were extracted. Pts with incomplete treatment and outcomes data or unknown race were excluded (n=87) as were n=157 who received treatments other than CHOP or R-CHOP. The primary outcome was overall survival (OS). Differences in baseline features and treatment category were analyzed using Chi-squared statistical analysis. Univariate & multivariate logistic regression analyses were performed for the entire population and cohorts matched by IPI, age, year of diagnosis and socioeconomic factors, to determine predictors of 2-year and 5-year survival. Results: A total of 618 pts with DLBCL (n=484 W, n=134 B) who received either CHOP (n=249) or R-CHOP (n=369) were included in the present analysis. Univariate analyses demonstrated that age 〉60 yrs, PS 32, ES32, presence of B symptoms, high LDH, and IPI score 32 but not race were each significantly associated with a poorer survival. In multivariate Cox analysis age 〉60 (Hazard Ratio (HR) 1.5, 95%CI 1.2–2.9), PS 32 (HR 2.6, 95%CI 2.0–3.5), and male sex (HR 1.2, 95%CI 1.0–1.5) (p=0.047) predicted significantly worse survival. Treatment with R-CHOP was associated with significantly better survival (HR 0.6, 95%CI 0.4–0.9). In multivariate models of pts treated with CHOP, white race was associated with significantly better survival (HR 0.6, 95%CI 0.4–0.9) (see Figure) while IPI scores 3–5 (HR 3.1, 95%CI 1.9–4.9) and male sex (HR 1.5, 95%CI 1.0–2.1) were associated with worse survival. However among pts treated with R-CHOP, IPI scores 3–5 (HR 3.2, 95%CI 1.8–5.7) and Medicaid insurance (HR 2.8, 95%CI 1.4–5.5) but not race or gender was associated with worse survival. In multivariate models of pts treated with CHOP, white race was associated with better survival (HR 0.6, 95% CI 0.4–0.9) while IPI scores 3–5 (HR3.1, 95% CI 1.9–4.9) and male sex (HR1.5, 95%CI 1.0–2.1) were associated with worse survival. Univariate & multivariate analysis of 2-yr OS and 5-yr OS also demonstrated that IPI scores 3–5, and all IPI components individually were associated with significantly worse survival. In both univariate and multivariate analysis, treatment with R-CHOP was associated with significantly better 2-yr (OR 2.9, 95%CI 1.8–4.6) and 5-yr OS (OR 1.8, 95%CI 1.2–2.9) irrespective of race or insurance status. Conclusion: Previous studies looking at racial differences in treatment of DLBCL showed that black pts present at a younger age,with more advanced disease and were less likely to be treated with combined immunochemotherapy. Our combined institutional study with a large cohort of black pts with DLBCL and detailed ascertainment of prognostic factors and therapy showed that treatment with CHOP is significantly associated with inferior survival in black pts. However, treatment with R-CHOP appears to overcome race as a prognostic factor and is associated with significantly improved survival in all pts subgroups irrespective of race and disease status. This suggests that potential biological differences in DLBCL biology may exist between W & B pts that are no longer prognostic with the addition of rituximab, which we are further exploring with DLBCL subtyping and a study of candidate single nucleotide polymorphisms. Disclosures: Flowers: Genentech/Biogen-Idec (unpaid): Consultancy; Celgene, Intellikine: Consultancy; Millennium: Research Funding. Foran:GlaxoSmithKline: Research Funding.

Description: We aimed to assess the usefulness of 18F-FDG PET in siting lymphoma involvement for CTCL patients. We retrospectively analyzed CTCL patients who had received a lymph node biopsy within approximately one month of a PET scan. Between 2003 and 2007, 19 CTCL patients (7 males, 12 females, age range: 4 – 70, median: 55) underwent a combined 56 PET scans. All studies were performed on GE Discovery LS 8 slice MDCT PET CT scanner or GE Discovery DST 16 slice MDCT PET CT scanner (Milwaukee, WI) and the images were interpreted on a GE AW or Xeleris workstation. The patients underwent whole body imaging from the head to foot at 4 minutes per bed position. Of these 19 patients, eight patients (four men, four women, mean age: 56.6, range: 49 – 70) received a lymph node biopsy following a PET scan that demonstrated elevated focal uptake (SUVs ranging from 2.2 to 9.9) in at least one lymph node. In four of the cases, the biopsied lymph node directly confirmed CTCL involvement sited in that node by PET scan (SUV 2.2 to 6.1). Three cases represented false-positive PET scans which were attributed to category 1 dermatopic lymphadenopathy and post radiation change. Despite these lack in correlations, in one case, PET sited adenopathy (SUV 9.9) in an inguinal node that biopsy pronounced benign. Further studies proved that a sampling error produced a false-negative biopsy. Despite the small sample, the study demonstrates the importance of PET imaging in staging patients with CTCL. Findings suggest that lymph node SUV values ranging from 2.2 – 9.9 often correlate with definite involvement of the nodes, and consequentially progression of the disease. It was found that false-positive PET scans may result from post radiation change or dermatopathic lymphadenopathy, category 1. The sample size was too small to detect differences in SUV and correlation in lymph node involvement. Our study demonstrates the need for improvement in the specificity of FDG-PET scans possibly by two point imaging and accurate localization of lymph nodes by use of an intraoperative probe to further enhance its usefulness in the staging of CTCL. Further prospective study is needed to determine correlation with SUV and lymph node involvement.

Description: Abstract 1392 Poster Board I-414 Background: While African-Americans have a lower incidence of diffuse large B-cell lymphoma (DLBCL) than Whites (W) in the United States, there appear to be racial differences in clinical features, the use of chemoimmunotherapy(Flowers, AACR 2008), and treatment outcomes. However, previous analyses have been hampered by limited numbers of Black (B) patients (pts); lack of direct clinical information on pathology, prognostic factors, treatment, and outcomes; limited follow-up; or all three. Methods: To examine B/W differences in the use of CHOP-based chemotherapy vs. rituximab CHOP (RCHOP), we performed a retrospective, matched cohort analysis comparing the impact of race, on presenting features, treatment, and outcomes in a clinical setting with detailed data ascertainment from pathology, clinical, and pharmacy records. Patients diagnosed with DLBCL from 1981 to 2009 were identified from Emory pathology and medical records using previously published methods (Graiser, Cancer Informatics 2007). Baseline demographic data, components of the International Prognostic Index (IPI: age, performance status, lactate dehydrogenase [LDH], number of extranodal sites involved, stage), insurance status, employment status, treatment and survival data were extracted. Differences by race in baseline features and treatment category (CHOP vs. RCHOP) were analyzed using Chi-squared statistical analysis. Univariate and multivariate logistic regression analyses were performed for the entire population and cohorts matched by IPI, age, and year of diagnosis, to determine predictors of RCHOP use, 2-year and 5-year overall survival (OS). Cox regression was used to analyze the predictors of OS. Results: A total of 531 (348 W and 107 B) pts with a confirmed diagnosis of DLBCL were identified. The median age of diagnosis for B was significantly less than that for W pts (median age 46 (range: 18–87) vs. 56 (range: 18–86), respectively; p

Description: Abstract 5020 INTRODUCTION Positron emission tomography (PET) imaging using [F-18] fluorodeoxyglucose (FDG) provides metabolic information valuable to staging and restaging lymphoma patients. The Society of Nuclear Medicine recommends skull-base to proximal thigh imaging to survey the body and recommends vertex to toe PET/CT when the tumor may be in the extremities, e.g. melanoma (Delbeke 2006). As CTCL may develop in any region of the body, we aimed to assess the usefulness of vertex to toe PET/CT images in evaluating CTCL patients. METHODS We retrospectively analyzed 79 PET/CT scans from 33 CTCL patients (15 men, 18 women, age range: 7-83, median: 56) who were imaged between 2004 and 2008. All studies were performed on GE Discovery LS 8 slice MDCT PET/CT scanner or GE Discovery DST 16 slice MDCT PET/CT scanner (Milwaukee, WI) and the images were interpreted on a GE AW or Xeleris workstation by four board certified nuclear medicine physicians. RESULTS The length distribution of the 79 scans is detailed in Figure 1. The 79 scans showed an average maximum SUV of 8.6 +/- 5.2 (range: 2.3 – 21.7). Of the 79 scans, 15 scans showed only cutaneous involvement; 25 scans showed lymph node involvement (as defined by radiologic criteria of lymph node 〉 1.5 cm, and SUV 〉 2.5); 10 scans showed likely benign, non-specific uptake in the lymph nodes; 8 scans showed hypermetabolic lymphadenopathy (as defined by SUV〉 2.5, lymph node measurement

Description: Abstract 2006 Background: Mantle cell lymphoma (MCL) comprises 5–7% of all non-Hodgkin lymphomaand remains incurable with conventional chemotherapeutic approaches. Some clinical series and trials suggest that outcomes are improved with intensive induction containing cytarabine (Ara-C) and/or the use of high dose therapy (HDT) and autologous stem-cell transplantation (ASCT) once patients (pts) achieve remission. What is not apparent are the contributions of each and which prognostic factors influence outcomes. We examined our single center experience with initial management strategies for pts diagnosed with MCL between 1995 and 2011 and compared outcomes of CHOP±R (rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone), an intensive induction regimen HCVAD±R (rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate/cytarabine) in patients who subsequently underwent observation or HDT/ASCT. Methods: To examine the effectiveness of CHOP±R, HCVAD±R and HDT/ASCT, and the contributions of each to overall survival (OS), we conducted an IRB-approved retrospective review of consecutive cases of MCL identified from our database. Responsesfollowing the first management strategy were retrospectively assessed using International Working Group Criteria (JCO 1999). Descriptive statistics for the baseline characteristics of pts who received CHOP±R and HCVAD±R were compared using Chi-square tests. Kaplan–Meier estimation was used to evaluate OS and the treatment regimens were compared with the log-rank test. Toevaluate prognostic factors and the effects of treatment on OS, Cox proportional hazards models were used controlling for sex, race, stage, presence of B-symptoms, MIPI score, and those who underwent consolidation with HDT/ASCT. Results: 103 ptswere identified with a median age of 58 (range 32–79 years), 27% were ≥65 years of age, 80% were male, 77% were white, 96% had an ECOG PS ≤1, 93% were advanced stage (III/IV), and the majority had a low risk MIPI score (53%). 43% (N=44) received CHOP±R (mean # of cycles 5.3, median 6, range 1–8) and the remaining 57% received HCVAD±R (N=59, mean # of cycles 4.5, median 4, range 1–12). 65% of HCVAD pts and 27% of CHOP pts received R. No significant differenceswere observed in the baseline characteristics of the two groups: age (59 years CHOP±R vs. 57 HCVAD±R, p=0.06), presence of B symptoms (32% vs. 31%, p=0.77), stage (III/IV, 91% vs. 95%, p=0.69), or MIPI score (low 50% vs. 56%, p=0.97). Of the pts who were consolidated with a transplant (N=47), median age was 58, 85% were male, 32% had B-symptoms, all had an ECOG PS ≤1, 26% had an LDH〉ULN, 51% had a low MIPI, and 81% received HCVAD±R as induction. In comparison to those observed, the only significant differences were ECOG PS (8% ≥2, p=0.05) and induction regimen (63% CHOP±R, p