Citations

7555 Background: While CAR-T therapy is not myelo-ablative, patients with aggressive lymphoma treated with CD19 chimeric antigen receptor T cell therapy (CAR-T) are lymphodepleted and have prolonged B cell aplasia. The impact of CAR-T on immunologic protection from vaccine-preventable diseases (and thus the need to revaccinate) is not known. We report the vaccine titers of patients treated with axicabtagene ciloleucel (axi-cel) at Mayo Clinic. Methods: Retrospective chart review of adult lymphoma patients who received axi-cel from 9/2018 to 9/2020 for anti-viral and anti-bacterial titers prior to CAR-T infusion and at month 3 (MO3) post CAR-T. Results: Prior to CAR-T therapy, positive titer rate was highest for tetanus and lowest for Strep pneumoniae (Strep PNA) (Table). Similar trends were seen whether patients had stem cell transplant (ASCT) within 2 years of CAR-T (i.e. within immunization timeframe post ASCT) or not (Table). Compared to patients who had ASCT, those who did not had higher rate of positive titer for Strep PNA and lower rate for hepatitis B, Mumps, and VZV. The same trend for sero-positive rate were observed at MO3 post CAR-T. Patients with IgG<400 mg/dl received IVIG supplement for prophylaxis. Among the 23 patients who received IVIG, variable rate of conversion from negative to positive titers were seen for measles (1/2, 50%), mumps (2/3, 67%), rubella (2/3, 67%), varicella-zoster (VZV, 3/3, 100%), hepatitis A (6/6, 100%), hepatitis B (6/7, 86%) and Strep PNA (0/10, 0%). For patients who did not receive IVIG prophylaxis, there was one loss of seropositivity for Strep PNA (1/4, 25%). Conclusions: The presence of protective vaccine titers is variable for patients receiving CAR-T, regardless of recent ASCT. The loss of protective titers post CART was low. IVIG variably impacted vaccine titer status. Immunization remains important for patients with ASCT prior to CART, without completion of post ASCT immunization protocol. Further study is needed to inform the need for immunization and optimal timing post CART.[Table: see text]

7554 Background: Chimeric antigen receptor T-cell therapy (CAR-T) are commonly administered inpatient due to concern for early onset cytokine release syndrome (CRS), especially with axicabtagene ciloleucel (axi-cel). We report Mayo Clinic Rochester experience for hospital-based outpatient (HBO) management of patients (pts) receiving axi-cel and identify opportunities for improvement. HBO is closely integrated with inpatient practice and includes the same specialty trained clinical team. It is the first point of contact 24/7 for pts and triage evaluations. Lymphodepletion chemotherapy and CAR-T infusion is given on HBO followed by daily monitoring till day 8 and thereafter, as clinically needed until admission criteria is met. Methods: We retrospectively analyzed database of pts who received axi-cel between 1/2018 and 1/2021. After 06/2020, remote patient monitoring (RPM) tools were implemented to collect patient-reported neurologic symptoms and vital signs via bluetooth-enabled devices 4 times daily through month 1. Adverse data trends are addressed by the HBO team. Results: Among 72 recipients, 89% received their cells outpatient; 8% remained outpatient for the entire month. CRS and neurotoxicity incidence were comparable to those reported from CIBMTR. Median time to first admission was 2 days (Table). Use of bridging therapy, increased CRP and LDH were associated with early admission (≤3 days). Median time to tocilizumab, steroid, oxygen support, vasopressor was 4 days after admission. Half of HBO visits required intervention such as blood transfusions, IV medications through the first month. Nine pts had enrolled in RPM to date; with 8 having evaluable data. With 4 scheduled entries/day, a median of 1 entry/day was skipped and 2 entries/day were answered incompletely. An average of 57 additional unscheduled entries were generated per pt. Among a median of 373 (range 91-522) readings per pt over the first month, 4% (2%-20%) of the readings generated alerts. An average of 4 alerts were seen within 48 hours prior to admission. Data including additional subjects will be presented at ASCO meeting. Conclusions: We report a feasible outpatient care model for management of axi-cel recipients with safe outcomes. Clinical characteristics associated with more aggressive disease are associated with likelihood of early admission. Early RPM experience suggest use of digital tools could improve monitoring compliance and may predict evolution to symptoms requiring escalation of care.[Table: see text]

7542 Background: 60-70% of patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) can be cured with R-CHOP or R-CHOP-like immunochemotherapy. However, patients ≥80 years of age were either excluded or underrepresented in modern DLBCL trials, and their outcomes are understudied. The aim of this study is to define the survival trends and risk factors for inferior survival in older adult patients with DLBCL. Methods: Patients with newly diagnosed DLBCL were identified from the National Cancer Database (2004-2017, representing the rituximab era). Clinical characteristics, treatment, and outcomes were compared between patients ages ≥ 80, 65-79, and < 65 years. The Kaplan-Meier method and Cox proportional hazards model were used for survival analysis. Results: A total of 231,756 patients with newly diagnosed DLBCL were identified; 46,250 (20%) were ≥80 years, 87,702 (38%) were 65-79 years, and 97,904 (42%) were < 65 years. Patients ≥80 years were more likely to have a higher Charlson-Deyo Comorbidity Index score (CDS) (CDS ≥2, 12% vs 11% vs 8%, p = 0.001), less likely to receive systemic chemotherapy (63% vs 83% vs 89%, p < 0.001), and more likely to receive treatment at a non-academic center (71% vs 65% vs 48%, p < 0.001), compared to patients 65-79 and < 65 years, respectively. Median overall survival (OS) was significantly worse for patients ≥80 years compared to patients 65-79 years (11.6 vs 61.0 months, p = 0.001) and patients < 65 years (11.6 vs 178.1 months, p = 0.001). During the study period, the median OS had only minimally improved for patients ≥80 years (10.6 months in 2004-2007 vs 11.5 months in 2008-2011 vs 12.3 months in 2012-2016, p = 0.006). In contrast, the OS improvement appears more meaningful in patients 65-79 years (median in months: 51 vs 61.2 vs 65.9, p = < 0.001) and patients < 65 years (median in years: 14.6 vs 11.3 vs not reached, p < 0.001) in the prespecified intervals (2004-07, 2008-11, and 2012-16). In multivariate analysis, the most substantial risk factor for worse survival in patients ≥80 years was not receiving systemic therapy (hazard ratio [HR] = 3.26, 95%CI = 3.01-3.54, p = 0.001). Other risk factors associated with worse survival included high-risk IPI score (HR = 2.16, 95%CI = 1.96-2.39, p = 0.001), CDS score ≥2 (HR = 1.56, 95%CI = 1.40-1.73, p = 0.001), male sex (HR = 1.16, 95%CI = 1.09-1.24, p = 0.001), B symptoms at diagnosis (HR = 1.16, 95%CI = 1.08-1.25, p = 0.001), and treatment at a non-academic center (HR = 1.1, 95%CI = 1.01-1.20, p = 0.001). Conclusions: Patients ≥ 80 years of age with DLBCL have a significantly inferior survival which has not meaningfully improved in recent years. More than 1/3 of patients ≥ 80 years did not receive systemic therapy. Older adult patients with DLBCL should be assessed for fitness for chemotherapy using validated geriatric assessment tools. Novel therapeutic strategies with favorable safety profiles are urgently needed for this expanding patient population.

7530 Background: Clinical trials of novel salvage therapies (ST) have encouraging outcomes for relapsed/refractory classic Hodgkin lymphoma (R/R cHL) eligible for autologous stem cell transplant (ASCT). In this observational study, we report efficacies and outcomes of different ST in ASCT-eligible R/R cHL. Methods: Consecutive ASCT-eligible R/R cHL pts at 3 Mayo Clinic sites were included. Demographics and clinical variables at relapse were recorded by medical records review. Time to event endpoints were defined from relapse. Univariate associations were confirmed in multivariate models of age, sex, B symptoms, stage, bulky disease (BD, single mass > 6 cm) extra nodal disease (END), primary refractory disease (PRD) and early relapse (ER, within 1 year). Results: From Jan 2008 to May 2020, 207 ASCT-eligible pts with R/R cHL were included. Median age was 33 (24-43) years, 53% were male, 52% had advanced stage, 24% had BD, 36% had B symptoms, 41% had END, 11% had PRD and 43% had ER. All patients received ST and underwent ASCT; 43 (21%) received 2 ST, 14 (7%) 3 ST and 4 (0.5%) received 4 ST. 6 groups of ST were identified: ifosfamide, carboplatin and etoposide (ICE), bendamustine/brentuximab (BBV), brentuximab vedotin (BV), gemcitabine-based therapy (Gem), checkpoint inhibitor (CPI), and others. Table lists response to first line ST. BBV had significantly higher overall response rate (ORR) and complete response (CR) as first ST in univariate and multivariate models. 114 (79%) after ICE, 30 (97%) after BBV, 15 (56%) after BV, 25 (76%) after Gem, 8 (73%) after CPI and 15 (79%) after other ST underwent ASCT. Higher number of pts were bridged to ASCT after BBV than ICE (p<0.01). 110 (53%) went to ASCT in CR, 74 (36%) in partial response (PR) and 11% in progressive disease (PD). 43 received BV maintenance (BVm) after ASCT. Pts going to ASCT in PR or PD had significantly lower progression free survival (PFS) compared to pts in CR (2 yr PFS: 62%, 18% vs 77%, respectively, p<0.0001) in univariate and multivariate models. There was no difference in PFS and overall survival (OS) by type of ST. BVm was associated with higher PFS (HR 0.3 (CI95 0.2-0.8)) and higher number of ST was associated with lower OS (HR 2 (CI95 1.4-3)) in multivariate model (p<0.001). For pts transplanted in CR, there was no significant difference in PFS and OS by type of ST but higher number of ST predicted lower OS (HR 2.4 (CI95 1.2-3.5), p<0.01). Conclusions: Type of ST did not predict survival, response to and number of ST did. For pts with CR, number of ST not type of ST predicted survival. BBV had higher response rates, higher rates of bridge to ASCT, and may be a preferable ST than ICE. Large, randomized trials are needed to evaluate efficacy of BBV compared to ICE.[Table: see text]

6539 Background: The impact of insurance status on survival in diffuse large B‐cell lymphoma (DLBCL), the most common aggressive lymphoma, has not been evaluated after the implementation of the Affordable Care Act (ACA). The aim of this study is to compare overall survival (OS) in patients across insurance status groups and in the periods before and after the ACA. Methods: Adult patients with newly diagnosed DLBCL were identified from the National Cancer Database. The analysis was restricted to patients 64 years of age or younger as most patients 65 years or older are eligible for Medicare under the ACA. The 2004-2017 period was chosen to represent the immunochemotherapy era preceding and following the ACA. Logistic regression was used to explore associations between abstracted variables and insurance status groups. The Kaplan-Meier method and Cox proportional hazards model were used for survival analysis. Results: 93,692 adults (age < 64 years) with newly diagnosed DLBCL and known insurance status were identified (41.3% female, median age 54 years [range: 18 – 64], 81.8% White and 12.1% Black). 7,211 (7.7%) patients were uninsured, 64,744 (69.1%) had private insurance, 11,936 (12.7%) had Medicaid, and 9,801 (10.5%) had Medicare. When compared to insured patients (private insurance, Medicaid or Medicare), uninsured patients were more likely to have a median household outcome of < $38,000 [OR 1.93 (95% CI 1.79-2.07)], less likely to receive chemotherapy [OR 0.69 (0.64-0.77)], more likely to be male [OR 1.14 (1.07-1.21)], more likely to be non-White [OR 1.30 (1.20-1.40], and more likely to present with stage III or IV disease [OR 1.24 (1.16-1.32)]. Uninsured patients had an inferior OS [HR 1.21 (95% CI 1.15-1.27)] when compared to insured patients after adjustment for baseline comorbidity (Charlson-Deyo score ≥2), advanced stage, treatment with chemotherapy, and sociodemographic factors including sex, age, race, household income, facility type (academic/community), and location (urban/rural). With a median follow-up time of 14.8 years (95% CI 14.6-not reached), median OS was lower in uninsured patients [13.4 years (12.3-not reached) vs 14.8 years (14.7-not reached); p < 0.0001]. Despite the lack of major changes in DLBCL therapies, a diagnosis after the implementation of the ACA (in 2010 or later) was associated with a superior OS when compared with the outcomes of patients diagnosed in 2010 or earlier [HR 0.93 (95% CI 0.90-0.95)]. Similarly, five-year OS was superior in the insured group [HR 0.93 (95% CI 0.89-0.96)]. Conclusions: Uninsured patients with DLBCL and < 64 years old had inferior OS when compared with insured patients, and uninsured status emerged as an independent risk factor for inferior OS. Our data highlight the independent effect of insurance disparities - a potential indicator of variations in access to health care - on survival in DLBCL.

1503 Background: Patients with cancer and COVID-19 are at risk for poor clinical outcomes. An established multi-site remote patient monitoring (RPM) service was rapidly adapted to support a novel, interdisciplinary COVID-19 program for outpatient management of patients at high-risk for severe illness. The goal of this study was to assess the impact of the RPM program on clinical outcomes and acute care utilization in cancer patients diagnosed with COVID-19. Methods: This is a cross-sectional analysis following a multi-site prospective observational study performed at Mayo Clinic Cancer Center (MCCC). All adult patients with active cancer – defined as currently receiving cancer-directed therapy or in recent remission on active surveillance – and PCR-confirmed SARS-CoV-2 infection between March 18 and July 31, 2020 were included. RPM was comprised of in-home technology to assess symptoms and physiologic data with centralized nurse and physician oversight. Results: During the study timeframe 224 cancer patients were diagnosed with COVID-19 at MCCC. Initial management included urgent hospitalization (within 48 hours of diagnosis) in 34 patients (15%). Of the remaining 190 patients (85%) initially managed in the outpatient setting, those who did not receive RPM were significantly more likely to experience hospitalization than those receiving RPM (OR 3.6, 95% CI 1.036 to 12.01, P = 0.044). Following balancing of patient characteristics by inverse propensity weighting, rates of hospital admission for RPM and non-RPM patients were 3.1% and 11% respectively, implying that RPM was associated with an 8% reduction in hospital admission rate (-0.077; 95% CI: -0.315 to -0.019, P = 0.009). Use of RPM was also associated with lower rates of prolonged hospitalization, ICU admission, and mortality, though these trends did not reach statistical significance. Conclusions: In the midst of a global pandemic associated with inpatient bed, ventilator, and PPE shortages, the RPM program provided an effective strategy for outpatient clinical management and was associated with decreased rates of hospitalization, ICU admission, and mortality in cancer patients with COVID-19. This care model enabled simultaneous opportunity to mitigate the increased risks of exposure, transmission, and resource utilization associated with conventional care.

e19527 Background: While extra nodal involvement by MCL is relatively common, involvement of the central nervous system (CNS) is a rare ( < 5% of cases) complication with limited treatment options. We report the outcomes of a large cohort of patients (pts) with CNS MCL. Methods: MCL pts with CNS involvement seen at Mayo Clinic between 1/1/1995-9/16/2020 were identified. CNS involvement was defined by histologically confirmed CNS MCL, CSF analysis demonstrating lymphoma cells, and/or neuroimaging findings compatible with CNS lymphoma. Medical records were reviewed for baseline characteristics, treatment, and outcome. Kaplan-Meier method was used for time to event analysis. Results: Out of 1,753 pts with MCL, 36 (2%) had CNS involvement by MCL. Median age at MCL diagnosis was 64 years (range 36-83) and 26 were male (72%). At MCL diagnosis, non-CNS extranodal involvement was seen in 30 pts, 24 with 1 site and 6 with ≥ 2 sites; 24 had bone marrow involvement. 11 (31%) pts had blastoid variant. Median Ki-67 was 40% (range 15-100%). MIPI score was available in 17 pts [low risk (n = 5, 29%), intermediate risk (n = 9, 53%), high risk (n = 3, 18%)]. The most common frontline regimen for MCL was R-CHOP and 14 (39%) pts underwent autologous stem cell transplant in CR1. The incidence of CNS involvement was overall similar over the study period. Median time from MCL diagnosis to CNS involvement was 25 months (m) (range 0-167). 4 (11%) pts presented with CNS involvement at initial diagnosis and 32 presented at relapse (12 isolated CNS relapse and 20 concurrent CNS and systemic relapse. Abnormal CSF was noted in 27 (87%) pts [consistent with MCL diagnosis (n = 26), atypical lymphocytes (n = 1)]. Abnormal CNS imaging was reported in 27 (75%) pts [leptomeningeal (n = 18), leptomeningeal and parenchymal (n = 5), parenchymal (n = 2), ocular (n = 2)]. First line CNS-directed therapy data was available in 33 (92%) pts. 12 (34%) received intrathecal (IT) therapy alone, 19 (54%) received systemic +/- IT therapy, 2 (6%) received radiation alone, and 2 (6%) pts received no treatment (hospice). The overall CNS response to therapy was CR in 13 (42%) pts, PR in 3 (10%), SD in 8 (26%), and PD in 7 (22%) pts. Three pts received BTK inhibitors [ibrutinib (n = 2) or acalabrutinib (n = 1)] as the first CNS-directed therapy. One patient achieved a CR with a response lasting 4 m, another patient achieved a PR with response lasting 10 m. CNS response data was not available in the remaining pts. Median follow up from CNS involvement was 72 m (95% CI: 41-NR). Median EFS for the 1 st CNS-directed therapy was 3.7 m (95% CI: 1.6-6.1). At last follow up, 30 pts were deceased. The cause of death was CNS lymphoma in 10 (33%) pts and systemic lymphoma in 9 (30%) pts. Median OS from CNS involvement was 4.7 m (95% CI: 2.3-6.7). Conclusions: CNS involvement by MCL has dismal outcomes as evident by a median OS of approximately 5 m. BTK inhibitors may have a role in treatment of this rare complication, but further prospective investigation is needed.

Abstract Comparative data guiding initial therapy for Waldenström macroglobulinemia (WM), an infrequently encountered non‐Hodgkin lymphoma, are sparse. We evaluated three commonly used rituximab‐based frontline regimens: rituximab‐bendamustine (R‐Benda); dexamethasone, rituximab, cyclophosphamide (DRC); and bortezomib, dexamethasone, rituximab (BDR) in 220 treatment‐naïve patients with WM, seen at Mayo Clinic between November 1, 2000 and October 31, 2019. The median follow‐up was 4.5 (95%CI: 4–5) years. The R‐Benda cohort (n = 83) demonstrated superior overall response rate (ORR: 98%), in comparison to DRC (n = 92, ORR: 78%) or BDR (n = 45, ORR: 84%) cohorts, p = 0.003. Similarly, longer progression‐free survival (PFS) was evident with R‐Benda use [median 5.2 vs. 4.3 (DRC) and 1.8 years (BDR), p < 0.001]. The time‐to‐next therapy (TTNT) favored R‐Benda [median, not‐reached, 4.4 (DRC) and 2.6 years (BDR), p < 0.001). These endpoints were comparable between the DRC and BDR cohorts. Overall survival (OS) was similar across the three cohorts, p = 0.77. In a subset analysis of 142 patients genotyped for MYD88 L265P mutation, the ORR, PFS and TTNT were unaffected by the patients' MYD88 signature within each cohort. In conclusion, ORR, PFS and TTNT with R‐Benda are superior compared to DRC or BDR in treatment‐naïve patients with active WM. The patient outcomes with any one of these three regimens are unaffected by the MYD88 L265P mutation status.

AbstractIntroductionHypoalbuminemia is a known adverse prognostic factor in lymphomas. Yet, it is unknown if axicabtagene ciloleucel (axi‐cel) overcomes the adverse prognostic impact of hypoalbuminemia in relapsed/refractory large B‐cell lymphoma.MethodsWe conducted a retrospective analysis across three Mayo Clinic centers to assess the relationship of hypoalbuminemia (defined as a serum albumin (SA) levels ≤ 3.5 g/dL) on outcomes of patients treated with axi‐cel.ResultsThis analysis included 81 patients. Two patients had no available SA levels preceding axi‐cel infusion. Eighteen patients (22.8%) had hypoalbuminemia with a median SA of 3.3 g/dL. Patients with normal SA had a statistically higher ORR than those without hypoalbuminemia (P = .018). There was no difference in 1‐year PFS and OS between the group with hypoalbuminemia and the group with normal SA levels (48% vs 49%, P = .81) and (74% vs 73%, P = .97), respectively. There was no difference in the severity or median duration of cytokine release syndrome or neurotoxicity between the two groups.ConclusionNotwithstanding the limitations related to the relatively small sample size, axi‐cel therapy appears to overcome the adverse effect of hypoalbuminemia on OS and PFS. Large multicenter clinical studies are certainly needed to validate these findings.