Citations

Abstract B-cell chronic lymphocytic leukemia (B-CLL) is the most common leukemia in adults with CD19-targeting CAR T-cell therapy showing an excellent initial curative response. However, 10-20% of patients who receive anti-C19 CAR T-cell treatment experience relapse due to CD19 antigen loss. B-cell activating factor receptor (BAFF-R) that is expressed on the surface of normal and neoplastic B cells mediates the survival of mature peripheral B cells along with the B-cell receptor. Since B-CLL is characterized by apoptotic disruption and subsequent accumulation of mature B cells, BAFF-R is a logical, novel target for CAR T-cell therapy directed against B-CLL, especially if CD19 antigen loss occurs. In this study, we first manufactured BAFF-R CAR T-cells by infecting healthy donor Tnaïve/memory (Tn/mem) cells with BAFF-R CAR lentivirus before evaluating the antitumor activity of BAFF-R CAR T-cells on wild type MEC-1 (a B-CLL cell line), modified MEC-1, and primary cell lines. Antigen-specific cytotoxicity and activation of the BAFF-R CAR T-cells or control CD19 CAR T-cells were determined upon incubation with B-CLL cell lines and patient-derived primary B-CLL by measuring degranulation and IFN-γ release, respectively. BAFF-R CAR T-cells demonstrated substantial cytotoxicity against MEC-1, CD19-deficient MEC-1, and primary B-CLL cell lines; CD19 CAR T-cells showed no effect on CD19-deficient MEC-1 cells but did show effects with primary B-CLL and MEC-1 cells. Similarly, the release of IFN-γ was greater when BAFF-R CAR T-cells were co-cultured with CD19-deficient MEC-1 or primary B-CLL compared to CD19 CAR T-cells co-cultured with CD19-deficient MEC-1. In summary, BAFF-R CAR T-cells exert significant antitumor properties not only on patient-derived primary B-CLL cells but also on a CD19-deficient B-CLL cell line. We, therefore, assert BAFF-R-targeting CAR T-cells to be a novel therapeutic avenue for patients newly diagnosed with B-CLL and patients experiencing relapsed B-CLL after anti-CD19 therapy. Citation Format: Yan Luo, Kaihin Lui, Tommy T. To, Andrew liu, Farah Yassine, Mohamed A. Kharfan Dabaja, Martha E. Gadd, Hong Qin. Antitumor activity of BAFF-R targeting CAR T-cells on chronic lymphocytic leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2855.

7556 Background: The majority of R/R NHL progressions after CART involve pre-existing sites, suggesting a promising role for bridging radiotherapy (bRT). We assessed the local control rate of disease sites bridged with radiotherapy prior to CART and identified predictors of in-field recurrence. Methods: We retrospectively reviewed 35 patients with aggressive B-cell NHL who received bRT between leukapheresis and CART infusion between 2018 and 2021 at a multi-site single institution. bRT local control rate (LC), calculated based on the total number of irradiated sites, was defined from bRT end date. Progression-free survival (PFS) and overall-survival (OS) were defined from the date of CART infusion. In-field recurrence was defined as disease relapse occurring within the radiation planning target volume. Kaplan-Meier plots and cox regression modeling were used to estimate the desired output. Results: Median age of the cohort at time of CART infusion was 59 (range 19-73). The median equivalent 2 Gy dose (EQD2) administered was 23.3 Gy (range 4-41 Gy). The median time from end of bRT to CART infusion was 14 days (range 6-42). Five (14%) patients also received bridging chemotherapy with bRT. Among the 34 evaluable patients, 30 (88%) achieved an objective response (59% complete response and 29% partial response). At a median follow-up of 12 months, 1-year PFS was 48% and 1-year OS was 72%. No progression occurred beyond 240 days. On review of treatment plans and pre-treatment PET/CT scans, 59 sites were identified that received bRT prior to CART infusion. The median size and SUVmax of the irradiated sites were 8.7cm (range 1.5-22) and 13 (range 4-46), respectively. Of the 59 irradiated sites, 8 sites (13.6%) in 7 patients had in-field local recurrence, translating to 1-year LC of 84%. No in-field recurrence occurred beyond 180 days. Moreover, no local recurrence occurred in patients who received radiation to all known sites of active disease to EQD2> 30 Gy (n = 4 patients); these patients remained in remission except for 1 who experienced progression outside the bRT field. On univariate analysis, triple hit lymphoma (THL) (OR 22.8, 95% CI: 3.8-138.3; p < 0.001), tumor size (OR 1.25, 95% CI: 1.1-1.4; p < 0.001), specifically ≥ 9cm (OR 9.4, CI: 1.2-77.3; p = 0.036) and SUVmax (OR 1.1, CI: 1.02-1.15; p = 0.008), specifically ≥ 20 (OR 5.6, CI: 1.3-23.7; p = 0.018), were significantly associated with increased risk of in-field recurrence. On multivariate analysis, THL (OR 32.9, CI: 3.2-336.0; p = 0.03) and tumor size (OR 1.3, CI: 1.1-1.6; p = 0.01) retained significant association with in-field recurrence. Conclusions: Bridging radiotherapy prior to CART provides excellent and durable in-field local control for R/R B-cell NHL. Patients with triple hit histology and bulky disease are likely at higher risk of in-field recurrence and may benefit from higher doses of bRT.

e19049 Background: Prognosis of COVID-19 is poor in the setting of immunosuppression. Casirivimab/imdevimab (REGEN-COV), bamlanivimab, and sotrovimab are investigational monoclonal antibodies (MoAbs) authorized for treatment of mild/moderate COVID-19 for patients (pts) 12 years or older and who are at high-risk for progression to severe COVID-19. These neutralizing antibodies, against SARS-CoV-2 spike proteins, have been shown to decrease risk of progression to severe disease. Recipients of allogeneic stem cell transplants (allo-SCT) or chimeric antigen T cell therapy (CAR T cell) represent a high risk population. However, treatment outcomes with these MoAbs in these pts are not well described. Methods: This retrospective study included 33 consecutive adult pts who developed mild/moderate COVID-19 and received anti-spike SARS-CoV-2 MoAbs between December 2020 and November 2021. Allo-SCT (N=27) or CAR T cell (N=6) recipients were included, and outcomes were analyzed separately. Pts received REGEN-COV (N=19), bamlanivimab (N=11), or sotrovimab (N=1), missing (N=2). Results: In the allo-SCT cohort (N=27), median age at time of COVID-19 was 55 (23-76) years. Median time from allo-SCT to COVID-19 was 31 (22-64) months. Two pts received CAR T-cell therapy prior to allo-SCT. Diagnoses included leukemia or myeloid diseases (82%), lymphoma (11%), or myeloma (7%). Transplant characteristics are summarized (Table). Thirteen pts were vaccinated against SARS-CoV-2 prior to breakthrough COVID-19. Events considered included hospitalization due to COVID-19, disease progression, or death from any cause. The 6-month event-free and overall survivals were 81% and 91%, respectively. In the CAR T cell recipients cohort (N=6), 4 pts received axicabtagene ciloleucel for diffuse large B-cell or follicular lymphoma and 2 received brexucabtagene autoleucel for mantle cell lymphoma. The median follow-up was 8 (1-11) months. Two pts received autologous SCT prior to COVID-19. Median time from CAR T cell therapy to COVID-19 was 10 (3-24) months. Three pts were vaccinated prior to COVID-19. Only 1 pt was hospitalized due to severe COVID-19 requiring mechanical ventilation leading to death. Conclusions: These results show a potential benefit of MoAbs in high-risk pts, namely allo-SCT or CAR T cell recipients. Future studies should evaluate the role of prophylactic use MoAbs in these populations. A comparative analysis with a matched control cohort (who did not receive MoAbs) will be provided at the meeting. [Table: see text]

1512 Background: In response to the COVID-19 pandemic, many cancer practices adopted telehealth, including telephone and video appointments. Following a period of initial expansion that began in March 2020, sustained telehealth integration has emerged across the Mayo Clinic Cancer Practice (MCCP) in 2021. The primary objective of this study was to identify factors associated with utilization of telehealth appointments. Methods: A cross-sectional, multi-site, retrospective analysis was conducted across MCCP – a multisite, multiregional cancer practice with tertiary referral campuses in Minnesota, Florida, and Arizona, as well as rural, community-based hospitals and clinics throughout the Upper Midwest. Multivariable models were used to examine the association of patient- and provider-level variables with telehealth utilization. Results: Outpatient appointments conducted in July – August 2019 (n = 32,932) were compared with those from 2020 (n = 33,662) and 2021 (n = 35,486). The rate of telehealth appointment utilization increased from <0.01% in 2019 to 11.0% in 2020 and 14.0% in 2021. The strongest provider-level predictor of telehealth utilization was female physician provider type (OR 1.06, 95% CI 1.01 to 1.11; P = 0.0297), a trend consistently observed across career stages, practice locations and settings in 2020 and 2021. Additionally, while the rate of telehealth utilization was not significantly different at referral and community-based campuses in 2020, providers at referral campuses were significantly more likely to utilize telehealth than community-based campuses in 2021 (OR 1.1, 95% CI 1.01 to 1.12; P = 0.0289). Regarding patient-level factors, rural residence (defined by Rural-Urban Commuting Area codes), which accounted for 44.2% of the patient population, was significantly associated with lower telehealth utilization as compared to patients with urban residences, particularly for video appointments (OR 1.04, 95% CI 1.02 to 1.07; P < 0.0001). Notably, the disparity in telehealth utilization between rural and urban populations was found to be less pronounced in 2021 as compared to 2020. Conclusions: Multivariable analysis across a multi-site, multi-regional cancer practice identified several factors associated with increased telehealth utilization. These included female physician provider type, referral-based campuses, and patients residing in urban settings. A detailed understanding of the factors that influence telehealth utilization – a method of care delivery which represents a “new normal” across many cancer practices – will be essential to enable continued equitable access to high-quality, high-impact, patient-centered cancer care.

Immunoproliferative small intestinal disease (IPSID) is an uncommon disease with a higher prevalence in the developing world. IPSID diagnosis relies mainly on a tissue biopsy and a high index of suspicion. Treatment options are variable; however, they mainly include anthracycline-based chemotherapy with or without antibiotics in advanced stages. Because of the paucity of IPSID, our perception of the disease remains narrow, and investigating the optimal lines of therapy and prevention without a complete comprehension of the disease is challenging. In our review, we explore the expansion of knowledge about IPSID, which has been developing over the years, to help increase the detection of IPISD cases and further research the most appropriate lines of therapy and prevention.

AbstractPatients with relapsed follicular lymphoma who do not respond to CAR‐T have a poor outcome. We present a case of refractory follicular lymphoma who relapsed after two CAR‐T infusions and achieved a complete remission after treatment with obinutuzumab and lenalidomide. This represents a promising treatment option in the post‐CAR‐T setting.

Hodgkin lymphoma (HL) is an uncommon malignancy of B-cell origin. Classical HL (cHL) and nodular lymphocyte–predominant HL are the 2 main types of HL. The cure rates for HL have increased so markedly with the advent of modern treatment options that overriding treatment considerations often relate to long-term toxicity. These NCCN Guidelines Insights discuss the recent updates to the NCCN Guidelines for HL focusing on (1) radiation therapy dose constraints in the management of patients with HL, and (2) the management of advanced-stage and relapsed or refractory cHL.

SummaryThere have been no large studies comparing reduced‐intensity/non‐myeloablative conditioning (RIC/NMA) to myeloablative conditioning (MAC) regimens in T‐cell non‐Hodgkin lymphoma (T‐NHL) patients undergoing allogeneic transplant (allo‐HCT). A total of 803 adults with peripheral T‐cell lymphoma, anaplastic large cell lymphoma and angioimmunoblastic T‐cell lymphoma (age 18–65 years), undergoing allo‐HCT between 2008–2019 and reported to the Center for International Blood and Marrow Transplant Research with either MAC (n = 258) or RIC/NMA regimens (n = 545) were evaluated. There were no significant differences between the two cohorts in terms of patient sex, race and performance scores. Significantly more patients in the RIC/NMA cohort had peripheral blood grafts, haematopoietic cell transplantation‐specific comorbidity index (HCT‐CI) of ≥3 and chemosensitive disease compared to the MAC cohort. On multivariate analysis, overall survival (OS) was not significantly different in the RIC/NMA cohort compared to the MAC cohort (hazard ratio (HR) = 1.01, 95% confidence interval (CI) = 0.79–1.29; p = 0.95). Similarly, non‐relapse mortality (NRM) (HR = 0.85, 95% CI = 0.61–1.19; p = 0.34), risk of progression/relapse (HR = 1.29; 95% CI = 0.98–1.70; p = 0.07) and therapy failure (HR = 1.14; 95% CI = 0.92–1.41, p = 0.23) were not significantly different between the two cohorts. Relative to MAC, RIC/NMA was associated with a significantly lower risk of grade 3–4 acute graft‐versus‐host disease (HR = 0.67; 95% CI = 0.46–0.99, p = 0.04). Among chemorefractory patients, there was no difference in OS, therapy failure, relapse, or NRM between RIC/NMA and MAC regimens. In conclusion, we found no association between conditioning intensity and outcomes after allo‐HCT for T‐cell NHL.