Using individual patient-level data from the phase 3 VIALE-A trial, this study assessed the cost-effectiveness of venetoclax in combination with azacitidine compared with azacitidine monotherapy for patients newly diagnosed with acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy, from a United States (US) third-party payer perspective. A partitioned survival model with a 28-day cycle and three health states (event-free survival (EFS), progressive/relapsed disease, and death) was developed to estimate costs and effectiveness of venetoclax + azacitidine versus azacitidine over a lifetime (25-year) horizon. Efficacy inputs (overall survival (OS), EFS, and complete remission (CR)/CR with incomplete marrow recovery (CRi) rate) were estimated using VIALE-A data. Best-fit parametric models per Akaike Information Criterion were used to extrapolate OS until reaching EFS and extrapolate EFS until Year 5. Within EFS, the time spent in CR/CRi was estimated by applying the CR/CRi rate to the EFS curve. Past Year 5, patients still in EFS were considered cured and to have the same mortality as the US general population. Mean time on treatment (ToT) for both regimens was based on the time observed in VIALE-A. Costs of drug acquisition, drug administration (initial and subsequent treatments), subsequent stem cell transplant procedures, adverse events (AEs), and healthcare resource utilization (HRU) associated with health states were obtained from the literature/public data and inflated to 2021 US dollars. Health state utilities were estimated using EuroQol-5 dimension-5 level data from VIALE-A; AE disutilities were obtained from the literature. Incremental cost-effectiveness ratios (ICERs) per life-year (LY) and quality-adjusted life-year (QALY) gained were estimated. Deterministic sensitivity analyses (DSA), scenario analyses, and probabilistic sensitivity analyses (PSA) were also performed. Over a lifetime horizon, venetoclax + azacitidine versus azacitidine led to gains of 1.89 LYs (2.99 vs. 1.10, respectively) and 1.45 QALYs (2.30 vs. 0.84, respectively). Patients receiving venetoclax + azacitidine incurred higher total lifetime costs ($250,486 vs. $110,034 (azacitidine)). The ICERs for venetoclax + azacitidine versus azacitidine were estimated at $74,141 per LY and $96,579 per QALY gained. Results from the DSA and scenario analyses supported the base-case findings, with ICERs ranging from $60,718 to $138,554 per QALY gained. The results were most sensitive to varying the parameters for the venetoclax + azacitidine base-case EFS parametric function (Gompertz), followed by alternative approaches for ToT estimation, treatment costs of venetoclax + azacitidine, standard mortality rate value and ToT estimation, alternative sources to inform HRU, different cure modeling assumptions, and the parameters for the venetoclax + azacitidine base-case OS parametric function (log-normal). Results from the PSA showed that, compared with azacitidine, venetoclax + azacitidine was cost-effective in 99.9% of cases at a willingness-to-pay threshold of $150,000 per QALY. This analysis suggests that venetoclax + azacitidine offers a cost-effective strategy in the treatment of patients with newly diagnosed AML who are ineligible for intensive chemotherapy from a US third-party payer perspective. ClinicalTrials.gov, NCT02993523. Date of registration: 15 December 2016.

Background: The phase 3 VIALE-A trial (NCT02993523) demonstrated that venetoclax plus azacitidine (VEN+AZA) improved overall survival (OS) and led to higher remission rates compared with AZA monotherapy, in patients with newly diagnosed (ND) acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy. Based on the results from VIALE-A, VEN+AZA received full United States (US) Food and Drug Administration approval in October 2020 for patients with ND AML aged ≥75 years, or who were ineligible for intensive induction chemotherapy due to comorbidities. This study aims to assess the long-term cost-effectiveness value of the VEN+AZA regimen from the VIALE-A trial from a US third-party payer perspective.

Hepatitis B surface antigen (HBsAg) has recently gained traction as a biomarker that may provide prognostic information and inform treatment decisions in chronic hepatitis B virus (HBV) infection. It may be particularly useful when HBV DNA levels are low and therefore difficult to quantify accurately, either as a result of treatment or natural immune control of the virus. There are few published descriptions of the kinetics of HBV clearance, and most existing data come from Asia. We therefore set out to identify adults who cleared HBsAg in a UK cohort, to characterise those who clear, and to describe the dynamics of HBsAg clearance.

8060 Background: Lenalidomide may enhance anti-tumor immune responses by inhibiting Tregs and by augmenting NK-cell mediated antibody-dependent cytotoxicity. These immunologic effects may synergize when lenalidomide is combined with rituximab.METHODSWe are conducting a single center, open label phase II trial of lenalidomide and rituximab +/- dexamethasone in patients (pts) with indolent B-cell lymphomas or mantle cell lymphoma refractory to rituximab, defined as failure to respond to or progression within 6 months of rituximab-monotherapy, rituximab-containing chemotherapy, or rituximab-maintenance. The regimen consists of two 28-day treatment cycles of lenalidomide 10 mg daily +/- dexamethasone 8 mg once weekly (Part 1). During cycle 3, pts receive 4 weekly doses of rituximab 375 mg/m2 while continuing lenalidomide +/- dexamethasone (Part 2). After cycle 3, lenalidomide +/- dexamethasone is continued until disease progression, as tolerated. Peripheral blood is collected for immune assessment by flow cytometry at enrollment and after Parts 1 and 2.RESULTS37 pts enrolled on study; 23 pts completed Parts 1 and 2. Pts with CR or PR after Part 2 were analyzed as responders (N=16); pts with stable/progressive disease as nonresponders (N=7). After Part 1, CD4+FOXP3+ Tregs were increased in non-responders (median 1.3 fold change, range: 0.85, 4.6) but decreased or unchanged in responders (median 0.73 fold change, range: 0.02, 3.3); p = 0.07. The CD4+FOXP3+CD39+ Treg subset increased significantly in non-responders compared to responders (median fold change: non-responders 3.3, range: 2.8, 4.2; responders 0.98, range: 0.40, 3.5; p = 0.004). After Part 2, no further changes in CD4+FOXP3+ and CD4+FOXP3+CD39+ Tregs were observed.CONCLUSIONSNon-responding patients appear to have an increase in CD4+FOXP3+ Tregs after two months of lenalidomide +/- dexamethasone, particularly in the CD4+FOXP3+CD39+ subset. Responding patients exhibit no change in Tregs during lenalidomide and rituximab +/- dexamethasone therapy. Functional studies are underway to determine the significance of these findings.

Abstract 1402 Poster Board I-424 Introduction: Anatomic imaging using contrast-enhanced computed tomography (CT) is essential for management of lymphomas. Functional imaging using 18FDG-PET (PET) improves detection of certain lymphomas, specifically, diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). Currently, PET imaging is performed with co-registration of low-dose non-contrast enhanced CT images used for anatomic correlation and attenuation correction of PET images (PET/CT). It has been suggested that the low-dose non-enhanced CT cannot substitute for diagnostic contrast-enhanced CT imaging since the arterial and venous phases of contrast enhancement improve detection of lesions. Given the differential sensitivity for detection of specific lymphomas by PET imaging, we hypothesized that FDG could substitute for intravenous contrast in imaging of certain lymphomas, and that PET/CT or PET imaging could potentially obviate the need for contrast-enhanced CT. To test this hypothesis, we performed an independent and blinded radiology review of these imaging studies in patients (pts) with DLBCL, FL, small lymphocytic lymphoma/chronic lymphocytic leukemia (CLL/SLL) or marginal zone lymphoma (MZL) who had contrast-enhanced CT, PET, PET/CT, and low-dose non-enhanced CT available for retrospective review. Patients and Methods: Pts with a diagnosis of DLBCL, FL, CLL/SLL, or MZL with PET/CT and contrast-enhanced CT studies performed at the Hospital of the University of Pennsylvania within 6 weeks of each other without intervening therapy were studied. Pts with clinically suspected progression of lymphoma between studies were excluded. Radiologists, blinded to clinical information or other imaging results, separately interpreted image sets of low-dose non-enhanced CT, PET, fusion PET/CT, and contrast-enhanced CT studies. The presence or absence of disease at 44 nodal and 48 (female) or 49 (male) extranodal sites was recorded for each site for each imaging modality. Concordant findings across imaging modalities were defined as positive for involvement by lymphoma; discordant findings were reconciled using all available clinical and radiologic information with follow-up for progression or regression of abnormality, or by biopsy. Results: Between May 2006 and January 2008, 55 pts with either DLBCL (n=31), FL (n=13), CLL/SLL (n=5), or MZL (n=6) had complete images sets available for review. All patients had at least 18 months of clinical follow-up after imaging. A total of 282 sites met criteria for involvement by lymphoma. The rates of detection for specific lymphomas by each imaging modality are shown below: Conclusions: Our results suggest that combined PET/CT imaging is more sensitive than contrast-enhanced CT imaging for detection of DLBCL and at least as sensitive as contrast-enhanced CT imaging for detection of FL. In comparison, contrast-enhanced CT imaging appears superior to PET/CT imaging for CLL/SLL; while further studies are needed to confirm superiority of contrast-enhanced CT imaging in MZL. The routine use of both contrast enhanced CT and PET/CT modalities for staging of lymphoma may be unnecessary, potentially increasing both the cost of medical care and radiation exposure. Additional studies are needed to determine which imaging modality is optimal for each type of lymphoma. Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 1700 Poster Board I-726 Introduction Lenalidomide is an immunomodulatory drug with effects on the innate immune system that may enhance antibody-dependent cell mediated cytotoxicity as well as the development of specific anti-tumor immune responses. These immunologic effects may synergize with the action of rituximab. To test the efficacy of lenalidomide combined with rituximab, we are conducting a single center, open label phase II clinical trial in patients (pts) with indolent B-cell or mantle cell lymphomas previously resistant to rituximab. Patients and Methods Eligible pts must have relapsed/refractory indolent B-cell or mantle cell lymphoma with measurable disease that has failed to respond to or has progressed within six months of a standard course of rituximab monotherapy (375 mg/m2 weekly for at least four weeks) or a prior rituximab-containing chemotherapy regimen. Thus, all pts enrolled are considered rituximab-resistant. In Part I (lenalidomide + dexamethasone), pts receive two 28-day treatment cycles of lenalidomide 10 mg every day and dexamethasone 8 mg once weekly. After assessment of response to Part I, all pts receive a single course of rituximab 375 mg/m2, consisting of four weekly doses during cycle 3 (Part II: lenalidomide + dexamethasone + rituximab). Treatment with lenalidomide + dexamethasone continue during and subsequent to rituximab; stable and responding pts continue on lenalidomide + dexamethasone until disease progression or development of clinically unacceptable toxicity. Response assessment after Part II is performed three months after the first dose of rituximab. Results To date, 22 pts have started therapy; diagnoses included: follicular (n = 17), mantle cell (n = 2), small lymphocytic (n = 2), and marginal zone (n = 1) lymphomas; median age was 59 years (range: 35 - 72); male: female ratio was 5:6; median number of prior therapies was 3 (range: 1 - 7); LDH was increased in 23%. For 21 pts with at least one follow-up visit, there were 2 deaths and 2 episodes of disease progression. One death due to myocarditis occurred during Part I treatment; one death due to lymphoma occurred in a patient removed from study due to grade 3 rash, which subsequently resolved. Both episodes of disease progression occurred in pts with follicular lymphoma, one of whom had been removed from study during Part 1 because of thrombocytopenia attributed to myelodysplasia. For all patients, at a median follow-up of 5.0 months (range: 0.3 - 12.3), progression-free survival (PFS) is 81% (95% CI: 51-94). For 10 pts with response assessments after Parts I and II, overall response rate (ORR) after Part I was 30% (3 CR; 6 SD; 1 PD) and ORR after Part II was 70% (5 CR; 2 PR; 2 SD; 1 PD). At a median follow-up of 7.8 months (range: 5.0 - 11.9), PFS is 89% (95% CI: 43-98) for these 10 pts. For pts who completed Parts I and II, grade 3 or 4 non-hematologic toxicities included hypokalemia (2/10 pts), hypophosphatemia (1/10 pts), and hypocalcemia (1/10 pts); grade 1 tumor flare occurred in one pt with follicular lymphoma. Conclusions Based on these preliminary data in rituximab-resistant patients with indolent B-cell or mantle cell lymphomas, the combination of continuous daily lenalidomide, low-dose weekly dexamethasone, and a single four week course of rituximab during cycle 3, achieves a high overall response rate with relatively durable responses. Additional follow-up and correlative studies will be presented. Disclosures Off Label Use: Lenalidomide is used in this trial for treatment of lymphoma.. Downs:Genentech: Honoraria; Celgene: Honoraria. Nasta:Genentech: Speakers Bureau. Schuster:Celgene: Consultancy, Research Funding.

Although marginal zone lymphomas are relatively common, comprising 5% to 8% of all lymphomas, extranodal involvement of the subcutaneous fat is unusual. We report the F-18-2-fluoro-2-D-deoxyglucose-positron emission tomography/computed tomography, magnetic resonance imaging, and contrast-enhanced computed tomography appearance of extranodal marginal zone lymphoma involving the subcutaneous fat in a 49-year-old woman with a history of previously treated gastric marginal one lymphoma.

Background: Recent studies have prospectively established that concurrent or sequential addition of rituximab (R) to conventional therapies improves the overall survival rate (OS) for patients with low-grade follicular lymphoma (FL). However, there is little information regarding the prognosis of patients considered R-resistant. Subjects/Methods: We examined the records of 305 subjects with a diagnosis of FL seen at our institution between 1995 and 2007. To better define the prognosis for R-resistant subjects, we identified 133 subjects (grade 1, N=75; grade 2, N=41; grade 1 or 2, N=17) who completed an R-containing treatment (R alone, N=61; R combination, N=72) and had at least six months of follow-up from start of R-containing therapy. For the purposes of our study, we define R-resistance as progression of lymphoma within 6 months of the first R dose (i.e., the dose defining R-resistance) of the R-containing regimen followed by progression. Overall survival rates were evaluated for all subjects from first dose of R to last follow-up or death and, for R-resistant subjects, from the dose defining R-resistance to last follow-up or death. R-resistant subjects (N=62 [47%]) were subdivided into primary refractory (R-resistant after first R-containing treatment; N=30) or acquired resistant (R-resistant after at least one prior R-containing treatment without progression within 6 months; N=32). Median age at first treatment with R was 55 years (range: 21–87) for all subjects and 54 years (range: 21–87) for R-resistant subjects (for primary refractory, median=54 years [range: 28–87]; for acquired resistant, median=55 years [range 30–81]). The median number of prior non-R-containing treatment regimens was 1 (range: 0–4) for resistant subjects, and 0 (range: 0–3) for non resistant subjects. The median number of R-containing regimens for subjects with acquired resistance was 2 (range: 2–4). The frequency of large cell transformation did not differ between R-resistant and non R-resistant cohorts (N=7/71 [10%] and N=8/62 [13%], respectively). Results: Of 20 deaths observed for all subjects with FL receiving R or R containing regimens, 19 deaths occurred after R-resistance. At a median follow-up of 56 months (range 6–115) for all subjects receiving R, the median OS was not reached with 5-year Kaplan-Meier OS estimate = 81%. For R-resistant subjects, median OS from first dose of R defining R-resistance was 64 months (range: 6–100) with 5-year Kaplan-Meier OS estimate = 58%. Median rates of OS from R dose defining R-resistance were not significantly different between primary refractory and acquired resistant subjects. For subjects with acquired R-resistance, median time from first dose of R to first dose of R defining R-resistance was 10.4 months (range: 9–83). Conclusion: The OS estimate for subjects with R-resistant FL (5-year estimate OS = 58%) appears worse than survival estimates reported for unselected subjects with FL (5 year estimate OS = 80% for grade 1; 76% for grade 2 [SEER Survival Monograph, Non-Hodgkin Lymphoma]). This inferior prognosis seems unrelated to large cell transformation. Survival is similar for subjects with primary refractory and acquired resistance when survival is measured from the R dose used to define R-resistance.

Lymphomatoid granulomatosis is a rare lymphoproliferative disorder involving the lungs, skin and other organs. Advanced-stage disease does not tend to respond well to cytotoxic chemotherapy and is associated with a poor prognosis. We present a case of successful treatment of relapsed lymphomatoid granulomatosis with bexarotene, a novel retinoid agent.

Although marginal zone lymphomas are relatively common, comprising 5% to 8% of all lymphomas, extranodal involvement of the subcutaneous fat is unusual. We report the F-18-2-fluoro-2-d-deoxyglucose-positron emission tomography/computed tomography, magnetic resonance imaging, and contrast-enhanced computed tomography appearance of extranodal marginal zone lymphoma involving the subcutaneous fat in a 49-year-old woman with a history of previously treated gastric marginal zone lymphoma.

EBV is known to be detectable within a number of different tumors, though the exact relationship between the malignant cells and the EBV virus is unknown in most cases. In post-transplant lymphoproliferative disorders, which are clearly EBV-driven, EBV PCR of peripheral blood has proven to be a clinically useful tumor marker. The goal of our study is to determine the utility of novel EBV PCR panel in EBV associated malignancies. Subjects with suspected active or untreated EBV-associated malignancies were evaluated with a 6 assay EBV PCR panel targeting LMP-1, EBER-1 and EBNA-1 within both whole blood cells and plasma. EBV positive subjects and EBV negative control tumor samples are tested for LMP and EBER using traditional histochemical staining. LDH, SPEP, and traditional EBV serology are also measured. Of the 40 patients who were evaluated to date, 18 subjects showed evidence of elevated blood EBV viral load: 3/5 nasopharyngeal carcinoma, 3/4 angioimmunoblastic lymphomas, 3/6 Hodgkin's lymphomas, 4/10 peripheral T-cell lymphomas, 3/3 allogeneic bone marrow transplant lymphoproliferative disorders, 1/4 diffuse large B-cell lymphomas, 1/1 non-langerhans histiocytosis, and 0/7 low-grade B-cell NHL. Median DNA PCR copies/ml and ranges in EBV positive patients: EBNA plasma 500 (0–134,000), EBNA whole blood 700 (0–6,200), EBER plasma 200 (0–19,700), EBER whole blood 200 (0–1,000), LMP plasma 0 (0–600), LMP whole blood 0 (0–100). Patients were monitored with EBV PCR as they proceeded through treatment and 12 subjects are evaluable for response. Changes in viral load appear to be highly correlated with clinical tumor response (p=0.0013). 7/7 patients achieving CR had concurrent resolution of their plasma and whole blood EBV viral load. 5/5 patients with persistent disease had persistent elevated plasma and whole blood viral load. EBV histologic studies on the tumor samples are pending. Our data suggests that EBV PCR may be useful in the management of patients with EBV positive malignancies. Further patient enrollment and evaluation is ongoing.

Primary cardiac lymphoma (PCL) is an extremely rare disease defined as a lymphoma strictly confined to the heart or pericardium without dissemination. We present the case of an 82 yr old male with newly diagnosed PCL and two years of subsequent follow up. This report highlights the utility of a multimodality imaging approach in the diagnosis and management of PCL.

According to reports in the literature since 1991, 5–30% of relapses of DLBCL and HL were identified by surveillance X-rays and CT scans in the post-remission setting. Recently, a large series of DLBCL relapses were analyzed and suggested that surveillance imaging can identify early relapse in a population of patients with a more favorable outcome (Leidtke et al, Ann Oncol 17: 909–913, 2006). We retrospectively evaluated 40 patients with relapses of HL and DLBCL after complete remission from three referral lymphoma practices between 2000–2006 at the University of Pennsylvania. Relapsed disease was identified after primary therapy or after salvage chemotherapy and high-dose therapy with autologous stem cell transplantation. These relapsed patients underwent post-remission surveillance CT scans with or without PET scans roughly every 3–4 months for the first 1–2 years and every 6–12 months thereafter for at least 5 years. Seventeen patients had DLBCL and 23 had HL. Among relapses, 22 (55%) were detected with surveillance imaging and 18 (45%) were detected by clinical findings (10 complaints of lymphadenopathy, 2 with B-symptoms, 2 with both B-symptoms and lymphadenopathy, 3 with pain, 1 with cough, 1 with physician-detected lymphadenopathy, and none by laboratory results alone). Among the asymptomatic relapses detected by surveillance imaging, PET scanning detected 4 cases of DLBCL (36%) and 3 cases of HL (27%) relapses not identified by other techniques. In summary, compared to prior reports, our series reveals a much higher proportion of relapses detected by surveillance imaging in both diseases. We have adhered to a protocol similar to the NCCN 2006 guidelines; including CT scans as a part of follow-up evaluation. This schedule is more intensive than surveillance reported in prior studies, perhaps accounting for our higher rate of radiographic relapse detection. FDG-PET scans performed in combination with follow-up CT scans detected additional early relapses not seen by CT scanning alone. Prospective screening studies looking at the role of FDG-PET scans combined with CT scans to detect earlier relapses is warranted. Whether early detection of relapse provides a survival advantage should be evaluated in larger prospective studies in both HL and DLBCL.

17520 Background: Although both 131I-Tab and 90Y-Iab are approved for treatment of pts with relapsed or refractory low-grade, follicular, or transformed NHL, a prospective randomized comparison of these two forms of RIT has not been performed. We retrospectively reviewed our experience using either agent in pts with NHL. Methods: Sixty-one pts with NHL who were treated with a single course of 131I-Tab (N = 22) or 90Y-Iab (N = 39) between 1999 and 2005 were included in this analysis. The median age was 61 y (range 21–83 y) and the median number of prior therapies was 5 (range 1–13). Overall, 27 pts had indolent NHL (20 follicular grade 1/2, 4 small lymphocytic, and 3 marginal zone), while 34 pts had aggressive NHL (22 diffuse large cell, 10 mantle cell, and 2 follicular grade 3). Among pts, 75% had stage III/IV disease, 52% had an elevated serum LDH, and 38% had bulky disease (>5 cm). These characteristics were similar for pts receiving either 131I-Tab or 90Y-Iab, with the exception of elevated serum LDH (64% vs. 33%, p = 0.02). Median follow up was 21 mos (range 3–55). Results: The overall response rate (ORR) was 44% with complete response (CR) in 21% of pts. The median time to progression (TTP) was 5 mos for all pts, 9 mos for responders, and 14 mos for CRs (range 4–55). Patients with indolent NHL had no difference in ORR, CR, or TTP from pts with aggressive NHL, but had a significantly longer OS (HR 0.37, p = 0.01). Elevated LDH was the only significant predictor of ORR (31% vs. 57%, p = 0.04). In multivariable analysis, elevated LDH was adversely associated with TTP (HR 2.0, p = 0.02) and OS (HR 2.7, p = 0.02) among both subgroups of NHL. We did not discern a difference in ORR, CR, TTP, or OS between 131I-Tab and 90Y-Iab, even when stratifying for serum LDH. Conclusions: RIT produced high response rates in heavily pre-treated pts with indolent or aggressive NHL. Elevated LDH is the most significant prognostic factor for ORR, TTP and OS in this population. Patients with an elevated LDH should be considered for alternative treatment approaches or clinical trials, including RIT in combination with chemotherapy or transplant. [Table: see text]

We conducted a retrospective analysis of 50 lymphoma patients (Hodgkin's disease and non-Hodgkin's lymphoma) who had an 18F-fluoro-deoxyglucose positron emission tomography (FDG-PET) scan after at least two cycles of salvage chemotherapy and before autologous stem cell transplantation (ASCT) at our institution. The patients were categorized into FDG-PET negative (N=32) and positive (N=18) groups. The median follow-up after ASCT was 19 months (range: 3–59). In the FDG-PET-negative group, the median progression-free survival (PFS) was 19 months (range: 2–59) with 15 (54%) patients without progression at 12 months after ASCT. The median overall survival (OS) for this group was not reached. In the FDG-PET-positive group, the median PFS was 5 months (range: 1–19) with only one (7%) patient without progression at 12 months after ASCT. The median OS was 19 months (range: 1–34). In the FDG-PET-negative group, chemotherapy-resistant patients by CT-based criteria had a comparable outcome to those with chemotherapy-sensitive disease. A positive FDG-PET scan after salvage chemotherapy and prior ASCT indicates an extremely poor chance of durable response after ASCT.