Khurana, Arushi

Background: Real world multi-institutional data of anti-CD19 CAR-T therapy from across the US shows similar response rates and toxicities as that of the registration trials. For axicabtagene ciloleucel (axi-cel), bridging therapy (BT) during CAR-T manufacturing was not allowed. Real world data shows that patients who received BT had lower complete remission (CR) rates, duraiton of response (DOR) and overall survival (OS). Whether the poorer outcome is due to the effect of the BT or the aggressive biology of the disease is unknown. Patients with lower disease burden had higher response rate in the registration study ZUMA-1 for axi-cel. We examined the impact of response to BT on CAR-T outcome. Specifically, we also describe our experience using polatuzumab vedotin, bendamustine and rituximab (Pola-BR), also a recently approved therapy for relapsed/refractory diffuse large B-cell lymphoma (DLBCL), prior to CAR-T as salvage (ST) and BT. Methods: A retrospective review of 63 patients who received axi-cel for NHL from June 2016 - March 2020 at Mayo Clinic, Rochester was performed. ST was defined as the last therapy prior to leukapheresis and grouped into categories - autologous stem cell transplant (ASCT), and non-ASCT (chemotherapy and immunotherapy) . BT was defined as lymphoma-directed therapy given between leukapheresis and CAR-T infusion. Response to all lymphoma-directed therapy was evaluated using 2014 Lugano criteria. Event free survival (EFS) was defined as time from axi-cel infusion to progression, next treatment, or death. Overall survival (OS) was defined as time from axi-cel infusion to death. Results: Patients received BT if there were concerns for symptomatic progression of disease during CAR-T manufacturing that would reduce the likelihood of eligibility to receive CAR-T. The decision and choice of BT was at the discretion of the treating physician. Sixty-eight percent (n=43) of the patients received BT (19 chemo, 24 immunotherapy). Demographics of the patients based on their response to BT are shown in table 1. More patients in the BT responder group had received chemotherapy as type of bridge (58% vs. 33%). With a median follow up of 12-months for those still alive, significant improvement in EFS was seen in patients who had partial response (PR) or stable disease (SD) to BT than patients who continued to progress (median 12 months vs. 3 months, p = 0.01) [Figure 1A]. OS however, was not significant between the two groups (median OS 18 months - responders vs. 12 months non-responders, p = 0.19) [Figure 1B]. We also describe in the case series below 11 patients who received Pola-BR in salvage setting (ST) and/or BT (Table 2). Due to the lymphopenic effects of bendamustine, it was avoided before T-cell collection if possible. Two patients, however, received bendamustine as part of Pola-BR for salvage therapy as its need was determined per the managing physician. Axi-cel was successfully manufactured for all 10 patients. One patient did not have measurable disease after Pola-BR BT and remains on observation. A second patient died before CAR-T infusion from progressive disease. Four of the nine patients treated with CAR-T remained in response. Updated outcome will be presented. Conclusion: While patients who received BT have worse EFS than those who didn't, having some control of lymphoma after BT was associated with better EFS compared to patients who continued to have progressive disease after BT. Preliminary data from Pola-BR case series shows 60% (6/10) patients achieved PR/SD before CAR-T infusion, but requires longer follow up for its impact on survival. Disclosures Bennani: Purdue Pharma: Other: Advisory Board; Kite/Gilead: Research Funding; Affimed: Research Funding; Verastem: Other: Advisory Board. Ansell:AI Therapeutics: Research Funding; Takeda: Research Funding; Affimed: Research Funding; Regeneron: Research Funding; Seattle Genetics: Research Funding; Bristol Myers Squibb: Research Funding; ADC Therapeutics: Research Funding; Trillium: Research Funding. Lin:Janssen: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Novartis: Consultancy; Celgene: Consultancy, Research Funding; Bluebird Bio: Consultancy, Research Funding; Juno: Consultancy; Legend BioTech: Consultancy; Merck: Research Funding; Takeda: Research Funding; Gamida Cells: Consultancy; Sorrento: Consultancy, Membership on an entity's Board of Directors or advisory committees; Vineti: Consultancy.

e15020 Background: Durable responses were seen in registration trials for CAR-T in NHL across poor prognostic groups including early relapse post stem cell transplant (ASCT). Multi-center reports of real-world practice noted patients who received BT prior to CAR-T had decreased survival. The impact of last ST and response to BT on clinical outcome are examined here. Methods: Retrospective chart review was performed on 47 patients who received axicabtagene ciloleucel from June 2016 – September 2019 at Mayo Clinic, Rochester. ST was defined as last therapy prior to leukapheresis and grouped into categories – non-ASCT (chemotherapy, and immunotherapy), and ASCT. BT was defined as therapy given between leukapheresis and CAR-T. Response to therapy was evaluated using 2014 Lugano criteria. Event free survival (EFS) was defined as time from CAR-T infusion to progression, next treatment, or death. Results: The ST distribution was 77% non-ASCT [chemo 66% (31), and immunotherapy 11% (5)], and 23% (11) ASCT. EFS was significantly prolonged for the ASCT (median not reached) vs non-ASCT (median 3.8 months, p = 0.03) despite no difference in median prior lines of therapy. This may reflect more aggressive disease in the non-ASCT arm, as time from start of ST to leukapheresis was shorter (median non-ASCT 2.2 months vs. ASCT 4.4 months, p = 0.0008). Patients received BT if there were concerns for symptomatic progression during CAR-T manufacturing that would reduce the likelihood to receive CAR-T. Sixty-two percent (29) patients received BT (11 chemo, and 18 immunotherapy). The EFS did not differ between the type of BT. However, patients who progressed after BT had worse EFS than those who achieved stable disease or partial response (median 2.8 vs 8.7 months, p = 0.03). Conclusions: Patients who received CAR-T as the next treatment after ASCT had better EFS than those after other types of ST. While patients who received BT have worse survival than those who didn’t, having some control of lymphoma progression with BT was associated with better EFS than those who continued to have progressive disease.

3028 Background: Chimeric antigen receptor T-cell (CAR-T) therapy induces complete remission (CR) in 30-40% of patients with non-Hodgkin lymphoma (NHL). However, for patients who do not achieve CR as their first response, predictors for achieving CR as best response can guide management between careful observation or early intervention. Increased absolute lymphocyte count to absolute monocyte count ratio (ALC/AMC) predicts better response rates and survival in NHL patients receiving chemotherapy and/or autologous stem cell transplant. We evaluated the prognostic impact of ALC/AMC in CAR-T therapy for NHL. Methods: This was a retrospective review of patients who received CAR-T for NHL from June 2016-August 2019. ALC/AMC was assessed at the start of lymphodepletion (LD) chemotherapy. The receiver operator curve (ROC) was used to determine the best cutoff for ALC/AMC in predicting CR at 3 months. Event-free survival (EFS) was defined from time of CAR-T infusion to relapse or death, whichever occurred first. Overall survival (OS) was defined from time of infusion to death of any cause. Results: Forty-seven patients received axicabtagene ciloleucel, with a median follow-up of 14 months. By ROC, ALC/AMC > 0.8 before LD chemotherapy was predictive of achieving CR at 3 months. Baseline characteristics were similar between the high (n = 30) and low (n = 17) ALC/AMC groups. Patients with an ALC/AMC > 0.8 at the time of LD chemotherapy were more likely to achieve CR at 3 months (46% vs. 12%, p = 0.01), 6 months (52% vs. 0%, p < 0.0005), and 12 months (42% vs. 0%, p = 0.01). Correspondingly, the EFS and OS were significantly shorter in patients with ALC/AMC≤0.8 vs. those > 0.8 (median EFS: 2 vs. 13 months, P < 0.0001) and (median OS: 15 months vs. not reached, P = 0.03), respectively. Association between ALC/AMC ratio and EFS and OS remained consistent in multivariate Cox models after adjusting for other prognostic variables, including abnormal lactate dehydrogenase and increased ferritin level at infusion day. Conclusions: ALC/AMC > 0.8 before lymphodepletion chemotherapy is a strong predictor for complete remission as well as improved event-free and overall survival for axicabtagene ciloleucel in NHL.

e14100 Background: Only 3-5% of adult cancer patients in the US enroll in clinical trials. Patients with organ dysfunction are often excluded from clinical trials, regardless of specific drug metabolism or relative function of the organ. The ASCO and the US FDA recommend modernizing criteria related to baseline organ function and comorbidities. In hematological malignancies, often the disease itself is the reason for organ function derangement. In order to better inform clinical trial eligibility and improve participation in the future, we evaluated the impact of baseline organ function on the potential eligibility for clinical trial enrollment for real world patients with newly diagnosed DLBCL. Methods: Consecutive, newly diagnosed lymphoma patients were offered enrollment from 2002-2015 into the Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence. This analysis is based on 1270 DLBCL patients receiving immunochemotherapy. Baseline organ function parameters were identified from the exclusion criteria for hemoglobin, absolute neutrophil count (ANC), platelet count, creatinine, and bilirubin reported in recent frontline trials in DLBCL (Table). Abstracted clinical labs from the MER were used to determine the percent of patients that would be excluded based on the criteria. Results: We determined that 11-23% of MER DLBCL patients receiving standard of care frontline therapy would have been excluded in the various trials utilizing baseline organ function alone (Table). Hemoglobin and renal function had the greatest impact on exclusion. Conclusions: Current national and international (phase II and III) trials are excluding up to 23% of patients from clinical trial participation based on organ function alone in DLBCL. These data will be useful in future clinical trial development to meet ASCO recommendations to increase trial accrual, while balancing the drug toxicities and patient safety. An online tool was developed based on these results to aid future trial development. [Table: see text]

BACKGROUND: Malignant lymphomatous involvement of the eye and its surrounding structures is a rare phenomenon. Due to the unique location, non-specific symptomatology, limitations for invasive procedures, physician experience, and significant effect on the quality of life related to vision, it poses many challenges in the diagnosis and management. Ocular involvement can be primary or secondary in lymphoma. Primary ocular lymphoma, based on its clinical and pathological characteristics, has been divided into 2 main groups: those involving the orbit and adnexal tissues including lacrimal gland, conjunctiva and cornea and, those affecting intra-ocular structures mainly vitreous and retina. We aim to evaluate the SEER database to assess patterns and outcomes in patients with primary ocular involvement with lymphoma. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients (≥18 years) diagnosed with primary ocular lymphomas between 1975 and 2016. B-cell and T-cell lymphomas with stage I disease and primary site labeled as ocular (orbital, retina, conjunctiva, cornea, choroid, ciliary, lacrimal gland) were included. Treatment effect (surgery, radiation, systemic therapy) was analyzed when available.Overall survival (OS) was estimated using the Kaplan-Meier method and compared using the Log-Rank test. Cox proportional hazards models were used for adjusted survival analyses. RESULTS: We identified 3610 patients with primary lymphoma of the eye and adnexa. The median age was 66 years (18-103). 70% of the patients were Caucasians, followed by Hispanic (10%). Slight female preponderance was noted (55%). Most common site of involvement was orbit (n = 2063; 57%) followed by conjunctiva (n = 986; 27.3%). 8% (n = 292) of the patients were noted to have bilateral involvement. MALT (n = 2208; 61.2%) was the most common histology followed by DLBCL (n = 576; 16%) and follicular lymphoma (n = 519; 14.4%). Other histologies were rare (see Table 1). Most common treatment modality was radiation (n = 2117; 58.6%). Systemic therapy was utilized in only about 25% of the patients. Radiation treatment was associated with improved survival HR = 0.44 (0.23-0.83 95%CI, p = 0.01). Interestingly, patients that received systemic therapy had worse survival in univariate analysis (p<0.05) but was not significant in multivariate analysis. Site-specific survival suggested conjunctiva had the best median OS (19 years [16.3 - 21.7 95% CI]), followed by orbital and lacrimal gland involvement (median OS 12 years [10.92-13.23 95% CI]) - Figure 1. Retina (median OS 1.9 years) and choroid/ ciliary body (median OS 6.3 years) involvement were associated with shorter survival (p<0.05). DISCUSSION: Ocular lymphoma is a rare occurrence. Overall MALT was the most common subtype followed by DLBCL and FL. Very few instances of Burkitt's lymphoma, T-cell, and CLL were identified. Site-specific data in our subset, albeit with low numbers, suggest worse survival in the ciliary body and choroid similar to what is seen within vitreoretinal involvement. Due to small numbers in our subset, this requires confirmation in a larger dataset to identify potential change in management similar to primary vitreoretinal lymphoma, which is now recognized and managed as primary CNS lymphoma. Patients receiving systemic therapy showed a trend towards worse survival, which may be explained by a selection bias for more aggressive disease. Our study highlights the small but relevant prevalence of primary ocular lymphomas and reports the interesting observation of different survival patterns based on the site of involvement. Disclosures Yazbeck: Celgene: Membership on an entity's Board of Directors or advisory committees; Gilead Sciences: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.

Introduction: Primary extranodal lymphomas of the salivary glands constitute 12% of head and neck lymphomas, and less than 5% of salivary gland neoplasms. Parotid gland is the most commonly involved structure. Mucosa-associated lymphoid tissue (MALT) lymphoma is considered the most common histology in parotid lymphomas and carry a favorable prognosis. In this study, we sought to explore the impact of histologic subtype on survival. Methods: The Surveillance, Epidemiology and End Results (SEER) database was used to identify patients (≥18 years) diagnosed with primary parotid lymphomas between 1975 and 2016. B-cell, T-cell, and Hodgkin's lymphomas were included. Treatment effect (surgery, radiation, chemotherapy) was analyzed when available. Only stage I lymphomas by Ann-Arbor staging system were included to ensure parotid gland as the primary site. Overall survival was estimated using the Kaplan-Meier method, and compared using Log-Rank test. Cox proportional hazards models were used for adjusted survival analyses. Results: A total of 1482 patients were included in the analysis. Median age was 66 years (18-102), and the majority were female (n=904, 61%) and Caucasian (n=1074, 72.5%). MALT was the most common histology (N=681, 46%), followed by follicular lymphoma (FL; N=407, 27.5%), and diffuse large B-cell lymphoma (DLBCL; N=310, 21%). Small lymphocytic lymphoma was the least common histology (CLL/SLL; N=3, 0.8%). A total of 1084 patients (73%) had surgery, 433 (29%) had systemic therapies and 691 (47%) had radiation. Median overall survival was 13 years [12-14.5; 95% CI]. Survival was different by histological type (Figure 1, P<0.001). Compared with MALT, DLBCL was associated with higher mortality (HR 2.05 [1.60-2.63], P <0.001), while FL was not significantly different (HR 1.11 [0.89-1.40], P=0.32); independent of other variables. In a multivariate model; surgery (HR 0.81 [0.66-0.99], P=0.042) and radiation (HR 0.67 [0.56-0.82], P <0.001), but not systemic therapies (HR 0.93 [0.76-1.15], P=0.55) were associated with lower mortality (Figures 2-4). Adjusted mortality decreased by a relative 3% annually (HR 0.97 [0.95-0.99], P=0.03). Conclusion: Primary parotid lymphomas are rare extranodal lymphomas affecting mostly elderly Caucasian women. Using a large population database, MALT was still the most common histology and carried a favorable prognosis with a median overall survival of greater than 10 years despite the high median age at diagnosis. DLBCL histology did significantly worse which highlights the need for potentially more aggressive interventions to improve outcomes. Surgery and radiation were associated with improved outcomes. Disclosures Yazbeck: Gilead Sciences: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees.