Durani, Urshila

Background: Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin lymphoma with historically poor outcomes. Induction therapy with high-dose methotrexate (HD-MTX)-based regimens followed by consolidation with autologous stem cell transplant (auto-SCT) has become the mainstay of treatment with overall response rates (ORR) of 69-87% and two-year overall survival (OS) of 66-70% reported in prospective clinical trials. Limited data are available regarding a maintenance approach with single-agent HD-MTX, particularly in patients who are not auto-SCT candidates. Herein, we describe a comparison of outcomes in patients with PCNSL who underwent HD-MTX-based induction followed by either HD-MTX maintenance or auto-SCT consolidation at Mayo Clinic, Rochester. Methods: Patients with a diagnosis of PCNSL who received HD-MTX as part of induction therapy at Mayo Clinic between October 2010 and June 2022 were identified. Patients with prior or concurrent diagnosis of systemic lymphoma were excluded. Primary endpoints were progression-free survival (PFS) defined as time from post-induction treatment initiation to relapse, progression, or death due to any cause; and OS defined as time from post-induction treatment initiation to death due to any cause. We compared baseline characteristics by post-induction therapy using descriptive statistics. The primary endpoints PFS and OS were evaluated using Kaplan-Meier curves and compared by risk scores using a log-rank test. Results: A total of 148 patients were identified (51% female, 95% white) with median age at diagnosis of 66 years (range 29-85), with 48 patients (32%) age > 70. Most patients had multifocal disease (n=89, 60%) and deep brain involvement (n=100, 70%) at diagnosis. Few had vitreoretinal (n=15, 10%) or CSF involvement (n=9, 6%) at diagnosis. Using the Memorial Sloan Kettering (MSKCC) prognostic score for PCNSL, 35 patients (26%) scored class 3 (poor prognosis), 85 (62%) scored class 2, and 17 (12%) scored class 1. In total, 117 patients (79%) received methotrexate, rituximab, and temozolomide (MRT) induction therapy, and the remaining 31 patients (21%) received methotrexate and rituximab (MR) induction therapy (Table 1). A total of 70 patients (47%) underwent consolidation with auto-SCT and 37 patients (25%) received maintenance methotrexate. The patients who received maintenance methotrexate had higher median age of 72 versus 62 years, higher proportion of patients older than 70 (54% versus 16%, p<0.001), higher proportion of MSKCC prognostic score class 3 patients (33% versus 17%, p=0.026), and trend towards higher proportion of patients ECOG 2 or higher (41% versus 29%, p=0.109). A higher proportion of patients who underwent auto-SCT received MRT (vs MR) induction (n=64, 91%) compared to those who received maintenance methotrexate (n=24, 65%, p=0.004) (Table 1). The median follow-up for all patients was 4.5 years. At 1-, 3-, and 5-years post-induction treatment initiation, the PFS in the auto-SCT cohort was 85.8% (95% CI 77.7-94.9), 81.0% (95% CI 72.0-91.0), and 74.6% (95% CI 63.3-87.9), respectively; and the PFS in the HD-MTX maintenance cohort was 88.6% (95% CI 78.7-99.8), 72.6% (95% CI 58.8-89.8), and 72.6% (95% CI 58.8-89.8), respectively. At the same time points, the OS in the auto-SCT cohort was 94.0% (95% CI 88.4-99.9), 81.3% (95% CI 71.8-92.0), and 76.0% (95% CI 65.0-89.0), respectively; and the OS in the HD-MTX maintenance cohort was 94.3% (95% CI 86.9-100.0), 87.5% (76.8-99.8%), and 82.4% (69.0-98.4), respectively. Overall, there was no significant difference in PFS (p=0.64) or OS (p=0.95) based on post-induction treatment (Figure 1). Conclusions: Our study demonstrates comparable outcomes in PCNSL between a post-induction treatment approach with maintenance HD-MTX and consolidation auto-SCT, even though baseline characteristics indicate that patients who went on to receive auto-SCT were younger and had overall better performance status. This suggests that maintenance HD-MTX is a reasonable, time-limited strategy for patients with PCNSL responding to initial induction therapy, particularly in patients who are not candidates for auto-SCT.

Introduction: Histologic transformation (HT) from follicular lymphoma (FL) to an aggressive lymphoma is infrequent but has unfavorable outcomes. Sarkozy et al. (J Clin Oncol, 2019) reported that approximately half of FL-related deaths within the first decade of diagnosis occurred following HT. Our recent analysis showed heterogeneous outcomes with median overall survival (OS) of 61 months (Day et al., ASH, 2022). Prognostic tools post HT would be clinically useful but development has been limited by small cohort sizes. Factors previously associated with outcomes following HT have included age, time to progression, prior therapy, anthracycline exposure, and early HT. Utilizing the Lymphoma Epidemiology of Outcomes (LEO) Consortium of Real World Evidence (CReWE), we describe patterns of care and evaluate other prognostic factors following HT. Methods: This multicenter observational cohort consists of prospectively enrolled patients in the LEO Cohort, and patients with HT retrospectively identified at LEO centers. Patients diagnosed with biopsy proven grade 1-3A FL at diagnosis, and a subsequent biopsy showing HT to an aggressive lymphoma (FL grade 3B, diffuse large B cell lymphoma [DLBCL], or high-grade B cell lymphoma [HGBCL]) between 2002-2022, were eligible for the study. Patients with a component of FL grade 3B, DLBCL, or HGBCL at diagnosis were excluded. HGBCL was defined as double or triple hit or another aggressive subtype. OS was defined as the time from HT until death from any cause and calculated via Kaplan-Meier. Associations between clinical factors at time of HT and/or diagnosis and OS were evaluated using Cox models. Cause of death was evaluated using a competing risk approach. Results: Overall, 328 patients were confirmed with HT during the study period, 41% were female, and the median age at HT was 63 years (interquartile range [IQR] 56-70). The median time from diagnosis to transformation (TDT) was 35 months (IQR 12-66). At HT, 88% had advanced stage disease (III-IV) and LDH was elevated in 49%, while few patients exhibited B symptoms (5%) and ECOG performance status was >2 in 9%. 23% did not receive systemic therapy prior to HT. For those with prior therapy, the median time from prior therapy to HT was 15 months (IQR 7-39). The most frequent treatment regimens following HT were CD20-CHOP (42%), followed by platinum-based salvage therapy (20%), R-EPOCH (10%), CD20-Benda (8%), R-Mono (4%), and R-Gem-Ox (3%). 50 (15%) patients underwent consolidation with autologous stem cell transplant, 3 underwent allogeneic transplant (30 platinum-based, 15 CD20-CHOP, 5 R-EPOCH, 3 Other), and 2 received CAR T-cell therapy (Figure 1). After median follow-up of 85 months from HT, 170 patients had died; 5-year OS was 52% and median OS was 65 months (95% CI: 55-107). Among 160 patient deaths, cause was most often lymphoma-related (progression, n=107 [63%]; therapy-related, n=14 [7%]) compared to non-lymphoma (n=20, 13%) or missing/unknown causes (n=29, 17%). Clinical factors at the time of HT that were associated with worse OS include: ECOG PS >2, age ≥70, IPI 3-5, and shorter TDT (<24 months), hemoglobin <10 g/dl and elevated LDH. A transformation to HGBCL was also associated with inferior OS (Table 1). OS did not significantly differ by gender, BMI, stage, presence of B-symptoms, absolute lymphocyte count, number of extranodal groups, presence of bulky disease at HT, or response to prior FL treatment. Factors at the time of FL diagnosis that were associated with decreased OS after HT included FLIPI score 3-5 (high risk), FLIPI 2 (moderate risk), and FL grade 3A at diagnosis. Exposure to any systemic therapy for FL prior to HT was associated with shorter OS, with the worst outcomes in patients receiving an anthracycline prior to HT. POD24 to frontline immunochemotherapy was associated with inferior OS after HT (Table 1). Conclusions: Patterns of care in Transformed FL are heterogeneous and vary greatly in intensity. These data confirm previous reports that age, early HT, and any systemic therapies prior to HT are negative prognostic indicators for OS. At HT elevated LDH, low hemoglobin, POD24 status, poor performance status, and HT to HGBCL were associated with poor outcomes following HT. These data provide a basis for future prognostic indices to identify patients with highest risk of lymphoma related mortality for whom study of novel treatments is greatly needed.

Introduction: Our group previously published that the infusion autograft inhibitor KIR2DL2 (CD158b+CD337-) and activating NKp30 (CD158b- CD337+) Natural killer (NK) cells receptors were predictors of clinical outcomes in lymphoma patients undergoing autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT) (Porrata et al. Leukemia Research 2019; 81: 1-9). To assess if these subsets of NK cells still hold clinical relevance, we set up to investigate their prognostic ability to predict clinical outcomes at Day 100 post-APBHSCT. Methods: 107 lymphoma patients who participated in our double-blind phase III trail (Porrata et al, Biology of Blood and Marrow Transplantation 2016; 22(6); 1017-1023) and had clinical assessment at Day 100 post-APBHSCT were included in this study. Nkp30 and KIR2DL2 at Day 100 were assessed by flow cytometry analysis. Results: With a median follow-up for the entire cohort from Day 100 was 94.7 months (range: 4.83-158.1 months). Figure 1 shows the overall survival (OS) and progression-free survival (PFS) based on the absolute numbers of KIR2DL2 and Nkp30 NK cells. At Day 100, patients with a KIR2DL2 < 0.08 and Nkp30 ≥0.19 experienced superior OS and PFS compared with patients with a Day 100 KIR2DLD2 ≥0.08 and NKp30 < 0.19. In the multivariate analysis both the KIR2DL2 [OS: HR = 1.767, 95%CI, 1.302-30.31, p < 0.04; and PFS: HR = 2.663, 95%CI, 1.108-6.403, p < 0.03] and Nkp30 [OS: HR = 2.594, 95% CI, 1.239-5.432, p < 0.01; and PFS: HR = 3.676, 95% CI, 1.875-7.206, p < 0.01] were independent predictors for OS and PFS. Conclusion: Day 100 inhibitory KIR2DL2 and activating NKp30 NK cells are prognostic immune-biomarkers in lymphoma patients undergoing APBHSCT.

Health insurance literacy (HIL) constructs are related to financial toxicity in patients with cancer.

11005 Background: Despite progress in the enrollment of underrepresented in medicine (UIM) individuals in medical schools, hematology/oncology (HO) remains one of the least diverse medical subspecialties. We evaluated current recruitment efforts and barriers to the inclusion of UIM individuals in HO fellowship programs. Methods: We conducted a national online survey of program directors (PDs) and associate PDs (reported in aggregate as PDs) of adult and pediatric HO fellowships. Each PD received a unique survey link via email and 4 email reminders over the 8-week study period. Interim results at 4-weeks are presented and summarized with descriptive statistics. Results: At a pre-defined interim time point of 4 weeks, 78 HO PDs participated (18% response rate) and 69 completed the survey (88% completion rate). Most self-identified as women (57%, n = 38) and White (55%, n = 37), were affiliated with an academic program (79%, n = 53), and led an adult HO fellowship (73%, n = 49). Most PDs reported under or no representation of UIM faculty in their divisions; 9% (n = 6) self-identified as UIM. PDs reported their HO fellowships matched a median of 3 UIM fellows over the last 5 years (IQR 2-5 over 5 years); 46% (n = 32) reported UIM recruitment was unchanged and 4% (n = 3) decreased during this period. About half of PDs (51%, n = 35), matched a UIM candidate in the 2023 match. Of the 21% (n = 14) of PDs whose programs had no UIM fellows, 0% matched a UIM applicant in the 2023 match. 52% (n = 36) of PDs endorsed an inability to match UIM applicants despite consistently ranking them highly. PDs perceive the top 3 barriers to UIM recruitment as: low number of UIM applicants (53%, n = 41), geographic program location (50%, n = 39), and lack of diverse faculty/fellows in their program (42%, n = 31). 10% (n = 7) also reported meeting resistance about DEI initiatives. While 53% (n = 41) of PDs believe fellow demographics should reflect the local population, 23% (n = 16) don’t know how to increase diversity and 11% (n = 8) do not believe their program’s diversity needs to increase. In answers to open ended questions, some PDs expressed disagreement with the definition of UIM and reported a perceived limited number of qualified UIM applicants. Almost all institutions provide DEI training (96%, n = 72) for faculty and most PDs believe it has improved recruitment and inclusion of diverse individuals (52% and 65%, respectively). Yet, 34% (n = 23) agree that UIM fellows in their program are treated differently because of their race/ethnicity and 22% (n = 15) agree that UIM fellows repress their identity or background to be respected by faculty, peers, and staff. Conclusions: Historically and currently excluded populations remain underrepresented in the HO workforce. PDs face multiple barriers to the recruitment of diverse fellows, including differing views on the definition of UIM and perception of the value of diversity in the physician workforce.

1533 Background: FDA-approved chimeric antigen receptor T-cell (CAR-T) and bispecific T cell engager (TCE) therapy are most commonly managed inpatient. Here we report our experience with hospital-based outpatient (HBO) management of patients (pts) receiving FDA-approved CAR-T or TCE and a predictive model for increased risk of early hospitalization (≤3 days post CAR-T). Methods: We reviewed the outcomes of pts who received FDA-approved CAR-T (axi-cel, brexu-cel, ide-cel, cilta-cel) or TCE (teclistamab) in the HBO unit between 3/2021 and 1/2023 at Mayo Clinic, Rochester. Results: 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. CAR-T and TCE are given on HBO followed by monitoring per REMS and as clinically needed until admission criteria is met. Remote patient monitoring (RPM) tools were used as part of outpatient monitoring. Out of 169 CAR-T pts, 87 (51%) were dosed with new indication/products (follicular lymphoma, mantle cell lymphoma, myeloma). Among those, 80 (92%) pts were dosed outpatient, among whom 21 (27%) were never hospitalized. CRS and ICANS incidences were comparable to that reported in registration studies. Median time to first admission from CAR-T infusion was 1 day (range, 0-9), with 31% (n=18/59) of admissions after day 3 post infusion. The most common cause of hospitalization was fever (n=40, 59%). Median length of hospital stay was 4 days (range, 1-49). Median time to tocilizumab (n=45, 80%), steroid (n=1, 2%), escalation of oxygen support (n=7, 12%), vasopressor (n=2, 3%), ventilator (n=1, 2%), hemodialysis (n=1, 2%) and ICU transfer (n=3, 5%) was 1 day (range, 0-31) after first admission. Use of bridging therapy, elevated CRP and LDH were predictive of early admission (ROC AUC 0.62). Four pts received teclistamab on HBO and enrolled in RPM. Data from more pts will be reported at ASCO. Conclusions: Our expanded study in CAR-T and TCE confirms that HBO is feasible and that CAR-T and TCE can be safely dosed outpatient. Approximately 31% of pts were admitted after 3 days from CAR-T infusion, and 27% of our pts were never admitted. Variables associated with aggressive disease can predict early hospitalization in pts receiving FDA-approved CAR-T. Extension of HBO practice to TCE is feasible.[Table: see text]