ALBERT

Description: Introduction: I-131-Tositumomab is a radiolabeled murine monoclonal antibody that binds to the CD20 antigen on the surface of malignant and normal B lymphocytes, targeting radiation to B cells. I-131-Tositumomab has been studied with chemotherapy and in high-doses as part of conditioning regimens for autologous stem cell transplant (ASCT) in relapsed/refractory B cell lymphoma patients (pts). Non-myeloablative I-131-tositumomab was approved in the US and Canada for treatment of CD20 antigen-expressing relapsed or refractory low-grade follicular or transformed non-Hodgkin lymphomas (NHL). Since February 2014, tositumomab and I-131-tositumomab, the Bexxar¨ therapeutic regimen, is no longer commercially available. Methods: We conducted a single-center, phase I trial of I-131-tositumomab in pts with CD20+ B cell NHL with relapsed or progressive lymphoma after ASCT. Eligibility criteria included creatinine grade 3 non-hematologic adverse event. After treatment, pts were monitored weekly for 13 weeks for hematological and other toxicities with response assessments at weeks 7 and 13, and then evaluated at weeks 26, 39, and 52, then every 3 months during year 2, every 4 months during year 3, every 6 months during year 4, and yearly thereafter. Results: 12 pts were enrolled and received both dosimetric and therapeutic doses of I-131-tositumomab; 6 pts (50%) were men. Median age was 58.5 years (range: 49-66). 5 of 12 (41.6%) pts had diffuse large B cell lymphoma (DLCBL), 4/12 (33.3%) follicular lymphoma (FL), and 3/12 (25.0%) FL transformed to DLBCL. Median number of prior therapies was 4 (range: 3 - 8); median time from ASCT was 1.6 years (range: 0.3 - 6.8). 2 pts had progressive disease after ASCT (1 transformed FL; 1 DLBCL); 10 pts had relapsed from complete remission (CR) after ASCT. 7 pts received 25cGy I-131-tositumomab. The cohort receiving 25cGy was expanded to 6 due to grade 4 neutropenia (1 pt), and then expanded to 7 because 1 pt progressed prior to week 7 response assessment. 3 pts received 50cGy and 1 pt each received 65cGy and 75cGy. At all doses, I-131-tositumomab was well-tolerated. Treatment-related toxicities 〉 grade 3 were exclusively hematological and not dose dependent, including thrombocytopenia (2/12: 1 grade 3, 1 grade 4), neutropenia (2/12: 1 grade 3, 1 grade 4) and anemia (2/12: 2 grade 3). Hematologic toxicities were reversible in all cases, with median time to recovery to 〈 grade 3 toxicity 7 days. Non-hematological adverse events were mild and 〈 grade 2. The most commonly reported non-hematological adverse event was fatigue. Overall response rate at week 7 was 41.6% (5/12) with 33.3% (4/12) pts achieving CR (2 pts with FL; 2 pts with DLBCL). Median duration of response was 13.8 months. As of May 2014, 2 pts are still in CR, including 1 pt with FL at 10.3 months and 1 pt with DLBCL at 5.5 years. Median progression free survival is 6.5 months; median time to treatment failure is 4.4 months. At the median follow-up of 21.9 months (range: 10.3 – 66.3), overall survival is 68.7%; no secondary hematologic malignancies have been observed. Conclusion: This is the first study of I-131-tositumomab RIT in pts with relapsed or progressive NHL after ASCT. In pts with CD20+ DLBCL, FL, or transformed FL following ASCT, non-myeloablative I-131-tositumomab is well-tolerated and can achieve sustained complete remissions. Table 1:Dose Escalation SchemaPlatelet count〉100,000, 150,000Dose level 120 cGy25 cGyDose level 240 cGy50 cGyDose level 355 cGy65 cGy Disclosures Schuster: GlaxoSmithKline: Research Funding.

Description: Background: Ibrutinib is a Bruton's tyrosine kinase (BTK) inhibitor that was recently approved by the FDA for treatment of patients (pts) with relapsed/refractory marginal zone lymphoma (MZL) who have already received one or more anti-CD20 containing treatment regimens and require systemic therapy. Approval was based on a clinical trial in 60 pts that showed durable responses and a median progression-free survival (PFS) of 14.2 months (mos) (Noy et al., Blood 2017). Since pts outside clinical trials may have different disease and demographic characteristics, our study investigates the safety and efficacy of ibrutinib when implemented in a non-trial setting. Materials and Methods: This is a retrospective analysis of MZL pts who received ibrutinib monotherapy as part of their treatment at the University of Pennsylvania. Subjects were identified by a database search for any MZL pts prescribed ibrutinib. Primary endpoints were PFS and overall survival (OS) since initiation of ibrutinib. Secondary endpoints were overall response rate (OR) and complete response rate (CR), adverse events, and reasons for discontinuation. The first patient was treated on April 10, 2014, and the data cutoff was July 1, 2019. Analyses were performed using STATA 15.0 software. Results: There were 28 pts included in this study with a median age of 69 years (range 36-90) and median ECOG performance status at diagnosis of 0 (range 0-2). All pts had advanced disease (all stage III/IV & 68% with bone marrow involvement). The distribution of MZL subtypes was 43% extranodal, 25% nodal, and 32% splenic. Most pts (89%) had received one or more treatments prior to ibrutinib (32% received first-line rituximab only). The median number of previous therapies was 2 (range 0-5), and 43% of pts were refractory to the previous line of therapy. A minority of pts (11%) received rituximab or another anti-CD20 antibody concurrently with ibrutinib. Pts started ibrutinib a median of 56 mos after their initial diagnosis (range 0.5-221 mos) with a median duration of therapy of 7 mos (range 0.7-62 mos). The median starting dose was 420 mg daily (range 70-560 mg daily). In 26 pts with response data available, the OR was 73% with CR 15%. The 12-mo PFS and OS were 77% and 87% respectively (see Figures 1 & 2, median PFS and OS not yet reached). PFS and OS at median follow-up were 55% and 69% respectively. There was no significant difference in response or survival rates among MZL subtypes. Pts who received rituximab only prior to ibrutinib had an OR of 86% compared to 69% in those with more than one previous therapy (Χ2 = 0.73, p = 0.39). Ibrutinib was discontinued in 43% of pts after a median of 2.9 mos (range 0.7-13.7 mos) due to disease progression (50%), intolerance (42%), or other reasons (8%). Most (67%) pts subsequently received other therapies. All pts who stopped due to toxicity were responding at the time of discontinuation. Ibrutinib was also temporarily held or dose-reduced in 46% of pts due to toxicity (77%), preparation for surgery (15%), or drug interactions (8%). One patient experienced acute rebound of symptoms until ibrutinib was restarted. Most commonly reported toxicities are summarized in Table 1. Grade 3 toxicities included pneumonia (7%), sepsis (4%), hemorrhage (4%), arthralgia (4%), fatigue (4%), URI (4%), and hepatitis (4%). Toxicities responsible for cessation of treatment were arthralgia, hepatitis, thyroiditis, and hemorrhage. There were no reported treatment-related deaths. Conclusion: To our knowledge, this is the first study to report the efficacy and safety of ibrutinib in a large cohort of MZL pts treated outside of a clinical trial. We found that the therapy was well-tolerated and observed response rates that compared favorably to those shown in the prospective clinical trial. Disclosures Hughes: AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Genzyme: Membership on an entity's Board of Directors or advisory committees; Acerta Pharna/HOPA: Research Funding. Dwivedy Nasta:47 (Forty Seven): Research Funding; Rafael: Research Funding; Millenium/Takeda: Research Funding; Debiopharm: Research Funding; Aileron: Research Funding; ATARA: Research Funding; Pharmacyclics: Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria; Roche: Research Funding. Landsburg:Celgene: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Curis, INC: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Curis, INC: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Speakers Bureau; Seattle Genetics: Speakers Bureau; Takeda: Research Funding; Takeda: Research Funding; Triphase: Research Funding; Triphase: Research Funding. Barta:Takeda: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Research Funding; Bayer: Consultancy, Research Funding; Mundipharma: Honoraria; Merck: Research Funding; Celgene: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Mundipharma: Honoraria. Chong:Novartis: Consultancy; Merck: Research Funding; Tessa: Consultancy. Schuster:Novartis, Celgene, Genentech, Merck, Pharmacyclics, Acerta, and Gilead: Other: Grants, Research Funding; Novartis, Nordic Nanovector, and Pfizer: Membership on an entity's Board of Directors or advisory committees; Nordic Nanovector, Pfizer, AstraZeneca, Loxo Oncology, Acerta, and Celgene: Honoraria; Novartis: Other: a patent (with royalties paid to Novartis) on combination therapies of CAR and PD-1 inhibitors.. Svoboda:AstraZeneca: Consultancy; Celgene: Research Funding; Incyte: Research Funding; Pharmacyclics: Consultancy, Research Funding; Kyowa: Consultancy; Merck: Research Funding; BMS: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding. OffLabel Disclosure: This paper looked at the effectiveness of ibrutinib, a Bruton's tyrosine kinase inhibitor, in treating patients with marginal zone lymphoma (MZL). Ibrutinib is FDA approved for MZL patients who have received at least one anti-CD20 containing therapy and now require systemic treatment. Some patients in the study had not previously received an anti-CD20-based therapy and received ibrutinib off-label.

Description: Introduction: FL is generally responsive to conventional-dose chemotherapy but long term disease-free survival (DFS) is uncommon. High-dose chemo-radiotherapy followed by ASCT has the potential to induce remission in this disease but the long-term benefit of this modality remains to be determined. Methods: Between 1990 and 2003, we transplanted 52 pts originally diagnosed with low-grade FL (31 grade 1, 21 grade 2). Twenty-five (48%) had biopsy-proven large cell transformation (FL grade 3 or diffuse large cell lymphoma) before ASCT. The median number of prior therapies was 2 (range: 1 to 7). Prior to ASCT, 45 pts (87%) were responsive to salvage therapy with 20 pts (38%) in CR. Five pts (10%) had chemo-resistant disease at the time of ASCT. High-dose regimens included BCNU-cyclophosphamide-etoposide (31%), melphalan/TBI (27%), and cyclophosphamide/TBI (25%). Thirty-eight pts (73%) received peripheral stem cells (PSCT) and 14 pts (27%) received autologous bone marrow (BM) with 4-hydroxyperoxycyclophosphamide (4-hc) purging in 9 cases (17%). The median age was 49 yrs (range: 29–65). Results: There was 1 treatment-related death during the first 100 days. After ASCT, 36 pts (69%) achieved a CR, 2 (4%) had a PR, and 7 (13%) had stable disease. Among those in CR, 20 (56%) had a CR pre-ASCT, 14 (41%) had a lesser response, and 1 (3%) was chemo-resistant. Median follow-up (f/u) of survivors was 5.3 yrs (range: 1.7 months to 12.4 yrs). The median overall survival (OS) has not yet been reached. The median event-free survival (EFS) is 3.4 yrs (range: 1.7 months to 12.4 yrs). Among complete responders, more than 50% are disease free at last follow-up (range 1.7 months to 12.1 yrs). Variables favorably affecting EFS and OS are age 〈 60 yrs (p = 0.007, 0.015 respectively), achievement of a CR after ASCT (p = 0.002, 0.001), absence of transformation (p = 0.038, 0.017), BM vs. PSCT (p = 0.042, 0.086), and 4-hc BM purging (p = 0.044, 0.059). Number of prior regimens, response prior to ASCT, type of preparative regimen, and addition of TBI, were not significantly associated with EFS, DFS, or OS. In multivariable analysis, achievement of CR after ASCT and age 〈 60 yrs are the only significant predictors of EFS and OS. Adjusted for age, 53% of pts with a CR after ASCT are alive and event-free at last f/u (range: 2.4 months to 12.4 yrs) (Figure 1). In contrast, the median EFS among pts without a CR is 0.5 yrs (range: 1.7 months to 5.3 yrs). Conclusion: ASCT is a reasonable therapeutic approach to FL, resulting in long term EFS for some pts, even with relapsed, refractory and/or transformed disease. In our experience, significant predictors of EFS and OS after ASCT are complete response and age

Description: Background: PMBCL is a unique subtype of aggressive B-cell lymphoma representing about 5% of lymphoma cases. The diagnosis is generally based on a combination of clinical features (e.g., mediastinal mass) and pathological findings on tissue biopsy (e.g., large neoplastic B-cells with variable CD30 positivity by immunohistochemistry). However, the histopathologic diagnostic criteria are not well defined and the distinction between PMBCL and diffuse large B-cell lymphoma (DLBCL) or gray zone lymphoma (GZL) involving the mediastinum can be challenging. Most PMBCL trials use the traditional diagnostic criteria for study entry. Specific treatment approaches based on results of these trials are designed for patients with PMBCL. In this study, we hypothesized that a gene expression based assay that characterizes the molecular signature of PMBCL using formalin-fixed, paraffin-embedded (FFPE) tissue may improve the diagnostic criteria and allow more accurate interpretation of results for lymphoma patients enrolled in clinical trials. Methods: This exploratory study compared the PMBCL diagnosis established by clinicopathologic criteria alone to the diagnosis assigned by a combination of clinicopathologic features and gene expression-based assay on FFPE tissue specimens of patients enrolled in a multisite phase I/II prospective trial using brentuximab vedotin (BV) in combination with rituximab - cyclophosphamide-hydroxydoxorubicin-prednisone (R-CHP) for CD30+ B-cell lymphomas (Svoboda, Blood 2017). The original diagnostic categories of PMBCL vs. DLBCL vs. GZL were assigned by investigators based on traditional clinicopathologic features. For exploratory Nanostring based diagnostic categorization, we used previously described and validated Lymph3Cx assay which consists of 64 probes with cut‐points defined at the 0.1 and 0.9 probability scores to distinguish between DLBCL and PMBCL (Mottok, Hematol Oncol 2017). The tissue was examined by a hematopathologist for adequate tumor content and nucleic acids were extracted from 10 mm FFPE scrolls or unstained slides. Survival curves were generated for PMBCL patients as categorized by investigator assessment alone and by investigator assessment plus molecular classification using STATA. Results: We enrolled 31 treatment-naïve patients with CD30+ B-cell lymphomas between January 2014 and April 2017 (NCT01994850). Based on investigator assessment, patients were categorized as PMBCL (N=23), DLBCL (N=6), and GZL (N=2). As of June 15, 2018, we obtained and analyzed diagnostic FFPE tissue using the Lymph3Cx assay on 14 pts with all 3 subtypes of CD30+ B-cell lymphomas: PMBCL (N=11), DLBCL (N=2), and GZL (N=1). Of 11 pts with PMBCL by investigator assessment alone, 8 pts (73%) had Lymph3Cx probability scores 〉 0.9 which was consistent with a diagnosis of PMBCL by gene expression; 2 pts (18%) scored in the indeterminate category (0.1 to 0.9); 1 pt (9%) scored as DLBCL (〈 0.1). All 8 pts with a concordant diagnosis of PMBCL by investigator assessment and gene expression assay achieved complete remission (CR) and remain progression free after completing BV+R-CHP with median follow-up of 18 months. However, 1 pt re-classified as DLBCL by Lymph3Cx and 1 of 2 pts with an indeterminate score by Lymph3Cx achieved only partial responses and ultimately progressed; 1 pt with an indeterminate score remains in CR. None of the non-PMBCL pts in our exploratory analysis (2 DLBCL; 1 GZL) as assessed by investigators were categorized as PMBCL by Lymph3Cx. The CR rate for patients categorized as PMBCL by investigator assessment alone was 82% compared to 100% in those categorized as PMBCL by both investigator and gene expression assay (Table 1). The reportable progression free survival would also be different for these two cohorts (Figure 1). We will complete Lymph3Cx testing of diagnostic tissue for all 31 enrolled patients with CD30+ B-cell lymphomas enrolled on our clinical trial by the meeting. Conclusion: Preliminary results of this ongoing study suggest that a diagnosis of PMBCL by clinicopathologic assessment alone that is not supported by molecular classification may include non-PMBCL pts and affect treatment outcomes. We recommend that future clinical trials for PMBCL include gene expression based diagnostic assays to improve diagnostic accuracy and interpretation of results. Disclosures Svoboda: TG Therapeutics: Research Funding; Kyowa: Consultancy; KITE: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Regeneron: Research Funding; Merck: Research Funding; Seattle Genetics: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding. Steidl:Seattle Genetics: Consultancy; Juno Therapeutics: Consultancy; Roche: Consultancy; Tioma: Research Funding; Nanostring: Patents & Royalties: patent holding; Bristol-Myers Squibb: Research Funding. Ruella:University of Pennsylvania: Patents & Royalties. Landsburg:Curis: Consultancy, Research Funding; Takeda: Consultancy. Dwivedy Nasta:Takeda/Millenium: Research Funding; Incyte: Research Funding; Debiopharm: Research Funding; Pharmacyclics: Research Funding; Rafael/WF: Research Funding; Aileron: Research Funding; Roche: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Merck: Other: DSMC. Barta:Janssen: Membership on an entity's Board of Directors or advisory committees; Merck, Takeda, Celgene, Seattle Genetics, Bayer: Research Funding. Chong:Novartis: Consultancy. Schuster:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis Pharmaceuticals Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Honoraria, Research Funding; Dava Oncology: Consultancy, Honoraria; Nordic Nanovector: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Honoraria, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees.

Description: Introduction: Chimeric antigen receptor T-cell therapy (CAR-T) is a revolutionary adoptive immunotherapy approach in lymphoma; however, there are substantial costs associated with CAR-T therapy. The current practice of admission for tisa-cel infusion and subsequent monitoring may contribute to these costs. Generally, our institution administers tisa-cel in the outpatient setting (Schuster NEJM 2017), and we now report our clinical approach and analyze the frequency of hospitalization post outpatient tisa-cel infusion with in the first 30 days of infusion. Patients and Methods: We conducted a single institution, retrospective study investigating hospitalization after CAR-T of adult lymphoma patients treated with commercial tisa-cel at the University of Pennsylvania between 6/2018 and 7/2019. Data collected included number and timing of hospitalizations, symptoms leading to hospitalization, diagnosis during hospitalization, and length of stay. Patients were eligible for inclusion if they had at least 30 days of follow-up after tisa-cel or hospitalization within the first 30 days after tisa-cel. Patients were followed for hospitalization events until progression of lymphoma. Admissions for elective surgical procedures were not included in hospitalization count. Patients received lymphodepleting therapy as an outpatient, followed by evaluation in clinic and outpatient infusion of tisa-cel. Indications for hospitalization at our institution included bulky disease, suboptimal organ function at time of tisa-cel infusion, or progressive lymphoma symptoms requiring inpatient management. After infusion, patients returned for follow-up on day 2 and day 4, then weekly starting day 8 through day 30 for physical examination, labs, and assessment for cytokine release syndrome (CRS) and neurotoxicity. Patients were instructed to contact our clinic with fever 〉 100.4F, any change in mental status, or for malaise. Patients were also required to stay within 1 hour driving distance of our clinic and have identified a caregiver who will remain with them for the first 28 days. Results: 30 patients with relapsed/refractory non-Hodgkin lymphoma who received commercial tisa-cel were identified; 28 (93%) patients received outpatient tisa-cel; two pts were admitted at the time of T-cell infusion due to progressive lymphoma symptoms requiring urgent management. The length of stay for the two patients who received inpatient tisa-cel was 17.5 days (17-18). Nine of 28 patients were admitted after tisa-cel infusion a median of 5 days after tisa-cel infusion (range: day +1 to +7). No patient required a second admission within 30 days. In most instances, 8/9 (89%) patients were referred for fever (fever range: 99.6F-102.0F) and one patient was referred for altered mental status. Of those hospitalized with fever, 5/8 (63%) patients had CRS and 3/8 (37%) patients had an infection. The patient with altered mental status was diagnosed with grade 3 neurotoxicity. One of the admitted patients died during hospitalization; however, this was due to progression of lymphoma after initial admission for an infection. There were no deaths due to tisa-cel related toxicity. Conclusion: Our experience suggests that treatment with tisa-cel in the outpatient setting is safe and feasible with close supervision and adequate institutional experience. After infusion, most admissions within the first 30 days were triggered by fever and the etiology of fever was either CRS or infection. Admission diagnoses matched prior experience with tisa-cel as previously reported. Disclosures Dwivedy Nasta: Millenium/Takeda: Research Funding; Aileron: Research Funding; Pharmacyclics: Research Funding; Rafael: Research Funding; Celgene: Honoraria; Merck: Membership on an entity's Board of Directors or advisory committees; ATARA: Research Funding; Debiopharm: Research Funding; Roche: Research Funding; 47 (Forty Seven): Research Funding. Hughes:Acerta Pharna/HOPA: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Genzyme: Membership on an entity's Board of Directors or advisory committees. Chong:Novartis: Consultancy; Tessa: Consultancy; Merck: Research Funding. Svoboda:AstraZeneca: Consultancy; Celgene: Research Funding; Incyte: Research Funding; Pharmacyclics: Consultancy, Research Funding; Kyowa: Consultancy; Merck: Research Funding; BMS: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding. Landsburg:Celgene: Membership on an entity's Board of Directors or advisory committees; Curis, INC: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Curis, INC: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Speakers Bureau; Seattle Genetics: Speakers Bureau; Takeda: Research Funding; Takeda: Research Funding; Triphase: Research Funding; Triphase: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees. Barta:Celgene: Research Funding; Mundipharma: Honoraria; Celgene: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Mundipharma: Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees; Merck: Research Funding; Takeda: Research Funding; Bayer: Consultancy, Research Funding; Seattle Genetics: Honoraria, Research Funding. Gerson:Seattle Genetics: Consultancy; Pharmacyclics: Consultancy; Abbvie: Consultancy. Ruella:Nanostring: Consultancy, Speakers Bureau; Novartis: Patents & Royalties: CART for cancer; AbClon: Membership on an entity's Board of Directors or advisory committees. Frey:Novartis: Research Funding. Schuster:Novartis: Other: a patent (with royalties paid to Novartis) on combination therapies of CAR and PD-1 inhibitors.; Novartis, Nordic Nanovector, and Pfizer: Membership on an entity's Board of Directors or advisory committees; Novartis, Celgene, Genentech, Merck, Pharmacyclics, Acerta, and Gilead: Other: Grants, Research Funding; Nordic Nanovector, Pfizer, AstraZeneca, Loxo Oncology, Acerta, and Celgene: Honoraria. Porter:Wiley and Sons: Honoraria; Immunovative: Membership on an entity's Board of Directors or advisory committees; American Board of Internal Medicine: Membership on an entity's Board of Directors or advisory committees; Genentech: Employment; Kite: Membership on an entity's Board of Directors or advisory committees; Glenmark Pharm: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees.

Description: 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.

Description: Abstract 2855 Background: Fludarabine-based therapies prolong survival of patients (pts) with chronic lymphocytic leukemia (CLL), but deplete CD4 T-cells causing immunosuppression which increases the risk of infection and may limit control of minimal residual disease by the immune system. Adoptive immunotherapy using autologous CD3/CD28-costimulated T-cells expanded ex vivo (ACTC) enhances immune reconstitution after fludarabine-based therapy of lymphoma (Schuster et al Blood abstract 2007). Methods: We conducted a multicenter phase I/II trial of ACTC following fludarabine-based therapy of CLL. After leukapheresis, pts received fludarabine-based therapy. 8 – 12 weeks after last chemotherapy, responding pts (CR, PR) received a single dose of ACTC prepared from autologous T-cells collected before chemotherapy. Results: 34 pts are enrolled (median age 61; male 24, female 10). To date, 19 pts are evaluable for studies of immune reconstitution at ≥90 days after ACTC infusion. Prior to ACTC, 11 pts received FCR and 1 pt FR as first therapy, while 5 pts received FCR and 2 pts FCR + bevacizumab for previously treated CLL. Median ACTC dose was 6.8E+9 CD3 cells (range: 4.88E+07 −1.05E+10). After chemotherapy, before ACTC infusion (day 0), median CD4 and CD8 counts for all evaluable pts were 119 (range: 12–573) and 80 (range: 4–682), respectively; 30 days after ACTC (day 30), median CD4 and CD8 counts were 373 (range 141–846) and 208 (range: 25–879), respectively. The increases in CD4 and CD8 counts between days 0 and 30 were statistically significant (p = 0.0003 for both CD4 and CD8 cell counts) and remained significantly increased between days 0 and 90 for both CD4 (p = 0.0004) and CD8 (p = 0.005) cell counts. ACTC dose was not associated with change in CD4 or CD8 count. Pts in complete remission (CR) at the time of ACTC infusion had significantly higher CD4 counts on day 30 than pts in partial remission (PR) [median day 30 CD4 count for CR = 464 (range: 194–846) vs PR = 190 (range: 141–395), p = 0.02], but not on days 0 and 90. There was no difference in CD8 counts for pts in CR or PR on days 0, 30, and 90. There were no SAEs; 1 pt developed AIHA after ACTC. For 19 evaluable pts at a median follow-up of 12 months (range: 3.2–22), PFS from ACTC infusion is 80%. Conclusions: ACTC infusion results in a dose-independent acceleration of CD4 and CD8 T-cell recovery after fludarabine-based chemotherapy compared to historical controls. CD4 counts on day 30 are significantly higher for pts in CR at the time of ACTC infusion. Further studies of immune reconstitution and function following ACTC are in progress. Disclosures: No relevant conflicts of interest to declare.

Description: BACKGROUND: Patients (pts) with follicular lymphoma (FL) who have progression of disease within 2 years of immunochemotherapy have poor outcomes and represent a distinct group for whom development of new therapies is warranted (Casulo et al. J Clin Oncol 2015). Autologous T cells genetically modified to express a chimeric antigen receptor consisting of an external anti-CD19 single chain murine antibody domain with CD3ζ and 4-1BB signaling domains (CTL019 cells) can mediate potent anti-tumor effects in pts with relapsed or refractory chronic lymphocytic leukemia, acute lymphoblastic leukemia, and B cell lymphomas. We evaluated the safety and efficacy of CTL019 cells in pts with relapsed or refractory FL as part of an ongoing phase IIa clinical trial (NCT02030834). METHODS: Eligible pts have CD19+ FL with progression of lymphoma

Description: Abstract 3962 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 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 continues 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: As of May 16, 2010, 27 pts have started therapy; diagnoses include: follicular (n = 18), mantle cell (n = 5), small lymphocytic (n = 3), and marginal zone (n = 1) lymphomas; median age is 60 years (range: 35–85); male: female ratio is 4:5; median number of prior therapies is 3 (range: 1 – 7); LDH is increased in 22% of pts. There were 2 deaths during protocol therapy: 1 death due to myocarditis during Part I treatment and 1 death due to lymphoma in a patient removed from study due to grade 3 rash, which subsequently resolved. One patient was removed from study during Part 1 because of thrombocytopenia attributed to myelodysplasia. One patient has not completed Part II response assessment. For 23 pts completing Parts I and II, median follow-up is 12 months (range: 3.1 – 25.3) with a progression-free survival of 78% (95% CI: 50 – 91) [Figure below]. Overall response rate (ORR) after Part I is 22% (3 CR; 2 PR; 16 SD; 2 PD); ORR after Part II is 57% (7 CR; 6 PR; 8 SD; 2 PD). After Part II, the ORRs by histology were follicular lymphoma 60% (9/15 pts), mantle cell lymphoma 50% (2/4 pts), small lymphocytic lymphoma 67% (2/3 pts), and marginal zone lymphoma 0% (0/1 pt). Grade 3 or 4 non-hematologic adverse events possibly related to lenalidomide include hypokalemia (4 pts), hypophosphatemia (3 pts), pneumonia (3 pts), fatigue (1 pt), elevated ALT (1 pt), elevated AST (1 pt), tumor flare (1 pt), pulmonary embolism (1 pt), and hyperuricemia (1 pt). Conclusions: These data indicate that 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 durable responses in rituximab-resistant patients with indolent B-cell or mantle cell lymphomas. Disclosures: Off Label Use: Phase II Trial of Lenalidomide - Dexamethasone - Rituximab in Relapsed or Refractory Indolent B-Cell or Mantle Cell Lymphomas Resistant to Rituximab. Schuster:Celgene: Research Funding.

Description: Abstract 3131 Introduction: Although MCL is reported to be an FDG-avid NHL subtype, PET-CT is not currently recommended in the modified IWG criteria (Chesen et al, JCO 2007) to stage, survey and assess treatment response in MCL. PET-CT is however frequently used for these purposes in clinical practice in MCL. Although convincing data exists regarding the prognostic utility of PET-CT imaging in Hodgkin Lymphoma (interim & post treatment) and DLBCL (post treatment), its prognostic utility both during treatment and immediately following treatment have not systematically been evaluated in a large MCL patient cohort to support its use in clinical practice. Methods: We conducted a two-center (JTCC & UPenn), retrospective cohort study to examine the prognostic utility of pre-treatment (PET-1), interim-treatment (PET-2 after 2–3 treatment cycles) and post-treatment PET-CT (PET-3) imaging in a uniform MCL patient cohort undergoing dose-intensive chemotherapy (R-HCVAD) or high-dose chemotherapy followed by autologous stem (ASCT) cell rescue in the 1st line setting. The primary study endpoints were PFS and OS. PET-CT images were centrally reviewed for the purposes of this study using standardized response criteria proposed by the Imaging Subcommittee of International Harmonization Project in Lymphoma (Juweid et al, JCO 2007). Radiologists were blinded to clinical outcomes at the time of PET-CT review and results were dichotomized at each time point and their concomitant SUV max at a suspected site of disease was recorded. Result: 82 pts (median age 61, range 35–95) with advanced stage (98% stage IV) MCL with PET-CT data were identified for this analysis. Of these, 57 pts were treated with R-HCVAD (50) or ASCT (7) in the first-line setting. 154 PET-CT scans were reviewed. Overall treatment response rate (IWG) was 93% (76% CR + 17%PR). With median follow-up of 23 months (disease progression) and 27 months (overall survival), 3 year PFS and OS estimates were 70% (CI 53–82%) and 82% (CI 65–91%) respectively. Median baseline characteristics: WBC 7.4, ECOG PS 1, LDH/ULN .82, Ki-67 (MIB-1) 28% (range 10–90%), MIPI 3.5 (31% intermediate risk, 19% high risk). 20% and 30% of pts were blastoid variant and leukemic phase at diagnosis respectively. Pre-treatment PET-CTs were FDG-avid in 92% of MCL patients with a median SUV max of 7.8 (range 2.4–36.7) at a suspected site of disease. Pre-treatment PET-CT SUV max was positively associated with high Ki-67 (variance-weighted least-squares regression, p=.01). PET-2 and PET-3 were positive in 34% and 18% of patients respectively. Kaplan Meier and Cox regression survival analyses were used to test the association between PET-CT and survival. Interim PET-CT status was not associated with PFS (HR 1.1, CI .4-3.6, p=.8) or OS (HR .8, CI .15-4.6, p=.8). Post treatment PET-CT status was statistically significantly associated with PFS (HR 5.4, CI 2.0–14.5, p=.001, Harrell's C =.70, Figure) and trended towards significant for OS (HR 3.2, CI .8-11.9, p=.1). Post treatment PET-CT status remained an independent predictor of PFS in multivariate analysis which included MIPI score, blastoid variant and Ki-67. Conclusion: Our cohort is the first large series of MCL patients treated essentially with R-HCVAD examining the correlation between PET-CT and outcome in the front-line setting. A positive PET-CT following the completion of therapy identifies patients with an inferior PFS and a trend towards inferior OS. These data do not support the prognostic utility of PET-CT in pre-treatment (no upstaging) and interim treatment settings. This information should be incorporated into the design of future prospective clinical trials. We are currently examining the relationship of novel computer-assisted quantitative FDG-PET/CT measures of total tumor volume and total tumor metabolic burden with clinical outcome in patients with mantle cell lymphoma. Disclosures: No relevant conflicts of interest to declare.