Kahl, Brad S.

Introduction: Health disparities negatively impact outcomes of patients (pts) with hematologic malignancies. Limited retrospective data correlating health disparities with lymphoma outcomes prohibit proper identification of reversible causes and elaboration of potential interventions. We present data from a coordinated effort between the National Clinical Trials Network (NCTN) cooperative groups (Alliance for Clinical Trials in Oncology [Alliance], Eastern Cooperative Oncology Group [ECOG], and the Southwest Oncology Group [SWOG]) to catalog the racial, ethnic, and socioeconomic characteristics of pts with lymphoma to better understand the quality of data collected, analyze selected health disparity indicators, and develop a prospective data collection tool. Methods: We conducted a retrospective analysis of demographic data from pts with lymphoma enrolled on 32 cooperative group therapeutic trials between 2005 and 2020. Special focus was placed on data regarding race, ethnicity, and proxies that help identify socioeconomic status (health insurance, residential zip code, Social Deprivation Index [SDI]). These were evaluated in relation to histology-based metrics from the Surveillance, Epidemiology, and End Results Program (SEER) Program with reported data through 2022. Here, our focus is to characterize baseline demographic and disparities data on the collection of these 32 NCTN lymphoma trials. Results: A total of 3,897 pts were included, with 3,406 non-Hodgkin lymphoma (87.4%) - 1,644 diffuse large B-cell (DLBCL, 48.3%), 905 follicular (26.6%), 669 mantle cell (19.6%), 113 primary central nervous system (3.3%), 75 T-cell (2.2%) - and 491 Hodgkin lymphoma (12.6%). Age at registration was available for 3,891 pts with median age 57.1 years (range: 18-92). The majority of patients were male (58.8%; one pt missing biological sex data). Race data were available for all but one patient, where most pts were white (W, 86.6%), followed by 246 African American (AA, 6.3%), 99 Asian (A, 2.5%), 13 American Indian or Alaska Native (AI, 0.3%), 8 Native Hawaiian or Pacific Islander (PI, 0.2%), 11 with more than 1 race reported (0.3%), and 145 with unknown/not reported race. Ethnicity data were unknown for 327 pts (8.4%) with 179 Hispanic or Latino (Hisp, 4.6%). Combined race/ethnicity data showed 3,010 non-Hisp white (NHW, 77.2%) and 219 non-Hisp black (NHB, 5.6%). For comparison, in the SEER database, 84.7% of all lymphoma cases were W, with 8.6% AA, 5.2% A/PI, 0.4% AI, and 1.1% unknown race, and with 13.9% of pts reported as Hisp. When focusing on the 804 pts enrolled on Alliance CALGB 50303 and ECOG-ACRIN 1412 studies, two randomized DLBCL studies, there was a more proportional representation of W and AA pts with DLBCL - 82.1% and 9.8% compared 84.6% and 7.7%, respectively, at SEER database, with 5.3% Hisp (with another 5.3% unknown) compared to 14.9% at SEER. Insurance information was missing in 113 pts. Of the remainder, 2,102 pts had private insurance only (55.6%), 549 with a mix of private and public (14.5%), 701 public only (18.5%, including 11.4% Medicare, 4.5% Medicaid, 0.8% both), and 166 self-pay (4.4%). Year-matched SDI score was available in 2,885 pts, where higher SDI scores = higher social deprivation. The total mean SDI score for the overall cohort was 42.5 with significant differences observed based on race/ethnicity and insurance type. Specifically, NHW were from less deprived areas (mean SDI=38.8) than NHB (66.4) or Hisp (65.5) (p<0.0001). Those without insurance (mean SDI=52.6) or only public insurance (48.9) were located in areas associated with greater deprivation compared to pts with private (40.1) or public+private (38.8) insurance (p<0.0001). Conclusion: To our knowledge, this is the largest retrospective catalog of racial, ethnic, and socioeconomic characteristics of pts with lymphoma enrolled on cooperative group therapeutic trials. The scope of NCTN cooperative group lymphoma studies provides a unique opportunity to assess novel therapeutic outcomes for patients representing racial, ethnic and socioeconomic subgroups with both common and rare lymphoma subtypes. From this resource, additional analyses on relationships between SDI, race/ethnicity, insurance coverage, disease subtype, and temporal trends will be presented. Support: U10CA180821, U10CA180882, UG1CA189823

Introduction: Scant data exist on prognostic factors, survival and treatment (Tx)-related outcomes in SCNSL. We conducted a multicenter international analysis to identify prognostic factors and outcomes in SCNSL at diagnosis (de novo), or after frontline Tx (1L) either with (concomitant) or without (isolated) systemic (syst) relapse. Methods: This study collected data from patients (pts) treated between 2001-2023 at 35 centers. Overall (OS) and progression-free survival (PFS) were calculated from SCNSL diagnosis to first event (death for OS, relapse/death for PFS) or last follow-up. Uni- (UVA) and multivariable (MVA) Cox analyses were performed to assess prognostic factors; Kaplan-Meier method was used to estimate survival. Results: 1173 (US: 863, UK: 273, Canada: 37) pts with SCNSL were included. Baseline characteristics were median age: 62 years (interquartile range 52.5-69), male sex: 58.7%, elevated LDH: 71.1%, stage III/IV: 88.6%, HIV: 3%, transformed LBCL (tLBCL): 13.8%, non-germinal center B-cell like (non-GCB) subtype: 52.3%, double expressor (DE): 40%, MYC rearrangement (MYC-R): 28.3%, MYC/BCL2 double hit: 16.6%, MYC/BCL2/BCL6 triple hit (TH): 6.1%. Among 522 pts with de novo SCNSL, 84.2% had involvement of a single CNS compartment (44.7% brain parenchyma; 40.4% leptomeningeal [lepto]). 1L regimens included 36.2% R-CHOP with high-dose methotrexate (HD-MTX), 12.5% MARIETTA-type, and 9.8% R-CODOX-M/IVAC; 54.6% received intrathecal chemotherapy. Consolidation Thiotepa-based autologous stem cell transplant (TT-ASCT) occurred in 15.3%. The majority of pts who underwent TT-ASCT had previously achieved CR or PR in syst (92.5%) and CNS (72.5%) compartments. At median follow-up 25.7 months (mos), subsequent relapse was observed in 27.5% TT-ASCT recipients: 36.3% had isolated CNS, 27.4% syst, and 36.3% concomitant. 588 pts presented with SCNS after 1L (66.2% isolated, 33.8% concomitant). Brain parenchyma involvement was observed in 56.8%, lepto in 22.6%. Tx included 31.6% HD-MTX combination (eg, R-MPV, MTR); 18.4% HD-MTX +/- rituximab; 16.2% MARIETTA-type; and 9.4% platinum-based regimen. Consolidation TT-ASCT occurred in 22.4% (n=132), and 13.8% (n=81) received CAR-T cell therapy (excluding subsequent relapses in de novo group). Syst (65.1%) & CNS (69.1%) responses (CR/PR) were higher before TT-ASCT compared to CAR-T cell (49.5% & 54.5%, respectively). After TT-ASCT, 52 pts (39.3%) relapsed, mainly in the CNS (n=30, 57.7%), with only 4 (7.7%) concomitant. After CAR-T, 48 pts (59.3%) relapsed: 15 (31.2%) isolated in CNS and 15 (31.2%) concomitant. 12-month cumulative incidence of relapse (with death as competing risk) was 21.1% after TT-ASCT and 55.8% after CAR-T. In 63 pts (5.4%), the first CNS event occurred >2 lines of Tx. With median follow-up of the entire cohort of 24.6 mos, median PFS and OS were 11 and 21 mos, respectively. mPFS and mOS were significantly better in pts with de novo SCNSL (13.4 & 47.4 mos) compared to SCNSL after 1L (10.4 & 14.2 mos) and >2 lines of Tx (6.5 & 9.7 mos); P<0.0001. Factors associated with significantly shorter OS in UVA across all presentations were age >60, male sex, GCB subtype, MYC-R, tLBCL, DE, TH, elevated LDH, ECOG PS ≥2, SCNSL after 1L (vs. de novo), and failure to achieve syst/CNS response to 1L. Of these, age >60, male sex, MYC-R, ECOG PS ≥2, and failure to achieve response to 1L remained significant in MVA. In de novo cases, age >60, DE, ECOG PS≥2, and failure to achieve syst/CNS response to 1L were associated with poorer OS; for pts with SCNSL after 1L, age >60, GCB subtype, and ECOG PS ≥2 were significant. Pts treated with HD-MTX-based regimens after 1L experienced longer OS than those treated with platinum regimens or high-dose cytarabine. In de novo cases, TT-ASCT was significantly associated with longer OS (HR=0.58; P=0.025) in MVA after adjusting for significant factors, 1L type, and response. For SCNSL at relapse, TT-ASCT (HR=0.34; P<.0001) and isolated SCNSL presentation (vs. concomitant HR=0.70, P=0.007) were associated with longer OS, adjusting for significant factors, type of second-line Tx, & site of CNS relapse. Conclusions: This study represents the largest analysis of SCNSL inclusive of all modes of presentation. Concomitant SCNSL at relapse was associated with poor outcomes, while TT-ASCT consolidation was associated with improved OS in de novo & relapsed disease. Despite advances in LBCL SCNSL remains an unmet therapeutic need.

Introduction: Adults older than 60 years constitute 20-25% of newly diagnosed classic Hodgkin lymphoma (cHL) and have inferior outcomes compared to younger patients (pts). Salvage therapy followed by an autologous stem cell transplant (ASCT) is a potentially curative option for pts with relapsed/refractory (R/R cHL). There is limited data regarding outcomes of older adults with R/R cHL who undergo ASCT in the current era where novel agents are employed in the R/R setting, in comparison with younger patients. Methods: This multicenter, international, retrospective study of 18 participating institutions included adults with R/R cHL who underwent ASCT from January 1, 2010 through December 31 2020. Retrospective chart review was performed to collect data on patient and disease characteristics at relapse, including lines and type of salvage therapy, pre-ASCT response by PET, and use of brentuximab vedotin (BV) as consolidation post-ASCT. Study objectives were to assess progression-free survival (PFS), overall survival (OS), and the probability of non-relapse mortality (NRM) with relapse as a competing event. NRM was defined as death without preceding relapse. Results: Of the total 1172 adults with R/R cHL enrolled in the parent cohort, 96 (8.1%) were age 60 years or older at the time of ASCT. In this older cohort, the median age was 66 years (range: 60-72). 54 (56%) were age 60-64, 31 (32%) were of age 65-69 and 11 (11%) were of age 70-72. 59 (61%) were male, 63 (66%) had advanced stage disease, 17 (18%) had bulky disease, 37 (39%) had B symptoms and 38 (40%) had extranodal disease. All patients (pts) received ABVD or ABVD-like frontline therapy. The median time to relapse was 6 months (range: 0-174). 48 pts (50%) relapsed within a year after completion of frontline treatment and 25 (26%) had primary refractory disease. Salvage therapy prior to ASCT included platinum-based chemotherapy (65%), BV-based regimen (34%), and PD-1 inhibitor-based regimens (3%). 16 pts (16%) underwent ASCT after >1 line of salvage therapy and 75 (78%) underwent ASCT after achieving a complete metabolic response (CMR). 14 pts (14.6%) received BV consolidation. Median follow-up for entire population was 53.4 months (range: 0.3-199.0). In older adults, the 5-year PFS was 54.2% (CI95: 43.4-67.6) not statistically different compared to pts <60 years (67.7% (CI95: 64.3-71.3), p=0.2). However, 5-year OS was inferior in older adults: 71.9% (CI95: 43.4-67.6) vs. 82.6% (CI95: 43.4-67.6) in pts <60 years (p <0.0001)). In pts ≥60, 26 (27%) died including 12 (12.5%) without preceding relapse. Older adults had 3-month, 1-year and 5-year probability of NRM of 5.2% (CI95: 2.2-12.2), 7.5% (CI95: 3.6-15.3), and 10.9% (CI95: 5.8-20.8), respectively. NRM was significantly higher in older adults compared to pts <60 who had 3-month, 1-year and 5-year probability of NRM of 0.3% (CI95: 0.1-1.0), 0.9% (CI95: 0.5-1.7), and 2.5% (CI95: 1.6-3.9), respectively (p<0.0001). Older adults had 3-month, 1-year and 5-year probability of relapse of 1% (CI95: 0.2-7.3), 7.5% (CI95: 3.6-15.3), and 28.6% (CI95: 19.1-42.1), respectively, which did not differ significantly from younger pts (p=0.3) who had 3-month, 1-year and 5-year probability of relapse of 0.6% (CI95: 0.3-1.3), 5.1% (CI95: 3.8-6.6), and 29.9% (CI95: 26.6-33.5), respectively. Conclusions: Although older adults with cHL are more likely to relapse after frontline treatment, only a minority of pts (<10%) in this large multicenter cohort underwent ASCT at age ≥60. In select older adults who underwent ASCT, the risk of relapse was similar to younger pts, but NRM was significantly higher, especially in the early post-ASCT period. Detailed assessment of comorbidity scores, toxicities of salvage therapies, and prognostic factors will be presented at the conference.

Mantle cell lymphoma (MCL) is a rare lymphoma with a median age at diagnosis of 60-70 years. Front line therapy has traditionally been bendamustine-rituximab (BR) in older patients and then Bruton Tyrosine kinase inhibitors (BTKi) for relapsed disease. Due to their efficacy, BTKi are now being combined with chemotherapy as induction treatment. The TRIANGLE trial of R-CHOP/R-DHAP +/- ibrutinib +/- transplant showed the benefit of adding a BTKi in young patients (Dreyling M, 2022). The SHINE trial, a phase III trial of BR +/- ibrutinib in patients >65 years, showed a significant improvement in median PFS (81 months vs. 53 months) (Wang M, 2022). However, this came with an increase in toxicity with more treatment related deaths in the ibrutinib arm (11% vs. 6%) and no difference in overall survival. Therefore, a better tolerated approach is still needed in older patients. A phase II study of rituximab + indefinite ibrutinib in 50 patients >65 years demonstrated efficacy of frontline BTKi with a 96% ORR and 71% CR (Jain P, 2021). However, a disadvantage of BTKi therapy is continuous treatment until disease progression or intolerance. In this study half of patients required dose reductions and almost a third of patients stopped treatment due to drug toxicity, most frequently atrial fibrillation or bleeding. If front line intermittent BTKi therapy is as effective as continuous therapy, it could minimize cumulative toxicity. A052101 (NCT05976763), an Alliance for Clinical Trials in Oncology trial, is a randomized phase 3 multicenter trial of upfront zanubrutinib that asks the question “in older patients with previously untreated MCL who obtain a CR with zanubrutinib-rituximab, is it safe and equally effective to stop treatment and restart it upon disease progression rather than continuing indefinitely?” The A052101 trial is enrolling pts with previously untreated MCL who are either >70 years old or 60-69 years old but are not transplant candidates due to cardiac ejection fraction <45%, DLCO <60% of predicted, creatinine clearance <70, Eastern Cooperative Oncology Group (ECOG) performance status of >2, or a Cumulative Illness Rating Scales score of >6. Key exclusion criteria include: history of a severe bleeding disorder or clinically significant cardiac arrhythmias. Patients will take zanubrutinib 320 mg daily and rituximab/rituximab biosimilar once monthly for 6 cycles. Patients with less than partial response after 6 cycles will go off study treatment. Patients with a complete remission will be randomized in a 1:1 manner to intermittent treatment versus continuous treatment. Randomization will be stratified by age (60-69 years vs ≥70 years) and MIPI score. Those randomized to the continuous arm will receive zanubrutinib until intolerance or disease progression. Those randomized to the intermittent arm will stop all study drugs after those initial 6 cycles and will restart zanubrutinib at first disease progression and continue it until intolerance or second disease progression. In order to make the study results generalizable to clinical practice, disease progression will be defined by clinical parameters rather than minimal residual disease testing. The primary objective of this study is to compare time from randomization to first progression or death (PFS1) in the continuous treatment arm to the time to second progression or death (PFS2) in the intermittent treatment arm. The primary evaluation will be to determine whether, for patients in a CR, active monitoring followed by retreatment with zanubrutinib therapy upon disease progression will result in non-inferior clinical outcomes compared to indefinite zanubrutinib. Serial quality of life testing and adverse event monitoring will be performed throughout the study to gain a full understanding of the impact of continuous vs intermittent zanubrutinib on patients' lives. A052101 has the potential to change management of older patients with previously untreated MCL. If our study demonstrates that the time to second progression/death when using the stop and retreat strategy is non-inferior to time to first progression/death when using continuous BTK therapy, then it might lead to a new standard of care in this patient population. This could result in decreased health care costs, decreased toxicity and improved quality of life for older patients with mantle cell lymphoma. Support: U10CA180821, U10CA180882; https://acknowledgments.alliancefound.org

Background: Approximately20% of patients with follicular lymphoma (FL) will experience disease progression or death within two years of years (POD24) of immunochemotherapy (IC) (Casulo et al, JCO 2015). A proportion of patients with POD24 have histologic transformation (HT), which heightens the risk of lymphoma-related death (Freeman et al, Blood 2019). To clarify the impact of HT on prognosis in POD24, we analyzed data from the Lymphoma Epidemiology of Outcomes (LEO) Consortium of Real-World Evidence (CReWE) to compare differences in outcomes among patients with POD24 with retained FL histology versus POD24 with HT. Methods: This was a multicenter study among 8 academic cancer centers. Eligible patients hadgrade 1-3a FL at diagnosis between 2003 and 2022, with POD24 following first line IC treatment with BR, R-CHOP, or R-CVP. POD24 was defined as disease recurrence within 24 months of IC. Patients with prior lines of treatment for FL were excluded. Patients with HT at first line IC were excluded. Biopsy at POD24 was obtained at the discretion of the treating physician. Three groups of POD24 were defined: POD24 with biopsy-proven retained FL histology (POD24_FL), POD24 with biopsy-proven HT to aggressive lymphoma (POD24_HT), and POD24 either without a biopsy or indeterminate histology on biopsy (POD24_I). We evaluated second-line treatments at time of POD24. Survival probabilities from second-line treatment initiation were estimated by the Kaplan-Meier method. Results A total of1,122 patients with FL were screened and308 patients with POD24 were identified.Median age at POD24 was 58 years (IQR 50-65).Among available data, race and ethnicity was reported as 76% non-Hispanic White, 3% non-Hispanic Black/African American, 9% Hispanic/Latino (any race), and 1% other minorities. First line therapy was R-CHOP in45% (140/308), BR in 33% (102/308) and R-CVP in 21% (66/308). Most patients (52%) had biopsy-proven retained FL at POD24 (162/308); 30% had no biopsy or indeterminate histology at POD24 (94/308), and 17% had biopsy-proven HT at POD24 (52/308). In the POD24_HT group, 52% received R-CHOP and 21% received intensive salvage chemotherapy as second line therapy. Patients with POD24_FL and POD24_I had similar rates of salvage chemotherapy (21% and 18%), BR (13% and 18%), R-CHOP (19% and 24%), and targeted therapies (8% and 5%), respectively, at second line. Consolidative autologous stem cell transplant was more common in POD24_HT patients at 21% versus 16% in POD24_FL and 6% in POD24_I. Patients with POD24_HT had significantly worse overall survival (OS) compared to POD24_FL (ref), with a hazard ratio of 3.79 (95% confidence interval [CI] 2.46-5.84), even after adjusting for age, FLIPI score, and first-line IC treatment. At 5 years, patients with POD24_HT had OS of 31% compared with an OS of 71% for patients with POD24_FL. Patients with POD24_I had similar outcomes to those with POD24_FL (5-year OS 75% versus 71%, respectively). Event-free survival (EFS) was also significantly lower in POD24_HT compared to POD24_FL: At 2 years, EFS was 27% for POD24_FL (21-35%) and 10% for POD24 _HT (4-23%). At 5 years, lymphoma remained the leading cause of death among patients with POD24, with 20% probability of lymphoma-related death in those with POD24_FL (95% CI 14.2-27.8) compared to 53% probability of lymphoma-related death in patients with POD24_HT (95% CI 40.6-70.7). Conclusions: In our multicenter cohort, we identified remarkable differences between the two biopsy-demonstrated entities of POD24 (i.e., with and without HT). Patients without a biopsy or indeterminate histology had similar outcomes as those with POD24_FL. Patients withearlyrelapse of FL after first-line IC remain a heterogeneous group with poor outcomes and a heightened risk of lymphoma-related mortality particularly compared with nonPOD24 groups. Even with retained FL histology, patients with POD24 had 20% probability of lymphoma-related death within 5 years of second-line treatment initiation. We demonstrate that poor survival is driven in part, but not entirely, by HT. Despite most patients receiving appropriate aggressive treatment, those with POD24_HT represent a distinctly vulnerable population warranting further study in directed prospective studies of both FL biology and clinical trials.

Background: The Phase 1/2 ECOG-ACRIN sponsored intergroup trial E4412 (NCT01896999) investigated brentuximab vedotin (BV) combined with the checkpoint inhibitors nivolumab (N) and ipilimumab (I) in patients with relapsed or refractory classic Hodgkin lymphoma (R/R HL). Here we present the safety and efficacy results for the cohort of pediatric patients aged 12-17 years. Methods: Patients were randomly assigned to treatment with the doublet of BV/N or triplet of BV/N/I, with the following dosing: BV 1.8mg/kg every 21 days for up to 16 cycles; Nivolumab 3mg/mg every 21 days for up to 34 cycles; Ipilimumab 1mg/kg every 9 weeks for up to 9 doses. Response evaluation by PET/CT was performed after 4 cycles. Transplant-eligible patients with CR could discontinue protocol therapy to receive a consolidative autologous stem cell transplant (ASCT). Results: Sixteen pediatric patients with a median age of 16 (range 12-17) were randomized. 75% of patients had received only 1 prior line of treatment with none having previously received BV and only 1 patient with prior ASCT. All patients were treated (8 in each arm) and included in the pediatric safety analysis cohort receiving at least one cycle of therapy. There were four reported grade (gr) 3 or greater toxicities: lymphopenia (gr 3) and neutropenia (gr 3) on the BV/N arm; and neutropenia (gr 4) and rash (gr 3) on the BV/N/I arm. Rash of any grade was more common in patients treated with BV/N/I (n=6) compared to BV/N (n=1). Peripheral sensory neuropathy was reported in 2 patients (BV/N, gr 2, n=2) There were no grade 5 toxicities. Fourteen patients (7 in each arm) were evaluable for response. The CR rate on both the BV/N and BV/N/I arms was 100%. The median survival follow up was 23.7 months (15.7 - 31.7). The 24-month PFS was 57% for BV/N and 100% for BV/N/I. Six patients (2 BV/N; 4 BV/N/I) discontinued protocol therapy to receive a consolidative ASCT. The 24-month PFS for patients consolidated with an ASCT was 100%, with all events occurring in patients randomized to BV/N, but not receiving an ASCT. Conclusion: Pediatric patients receiving both BV/N and BV/N/I had 100% CR rate with limited toxicity. Although this is a small cohort, there have been no progression events observed in patients treated with BV/N/I, including 3 patients treated without a consolidative ASCT.

Background: Due to recent advances, patients with follicular lymphoma (FL) have multiple treatment options with high response rates and durability. However, there is a gap in understanding how patient preferences influence treatment selection. To close this gap, we conducted a qualitative study using focus groups of adults with FL to understand their knowledge of treatment options, priorities, and decision-making process. We designed this study to inform the content of a planned discrete choice experiment in a larger population of patients with FL to better understand patient preferences and trade-offs around treatment delivery, side effects, outcomes, and quality of life. Methods: We conducted focus groups lasting 60-90 minutes, each with 3-5 participants recruited from the Lymphoma Epidemiology of Outcomes (LEO) Cohort Study. The LEO Cohort Study is a multi-institutional prospective cohort study of newly diagnosed adults with non-Hodgkin lymphoma from July 2015 to present. Each focus group was co-led by two investigators (U.D. and M.T.) and conducted using Zoom video technology. Participants were asked to comment on their understanding about FL and available treatments, their ideal treatment, their decision-making process about prior therapies, and quality of life and side effects associated with treatment. We performed exploratory content analysis of participant understanding of FL and their treatment preferences. We will continue to conduct focus groups until we reach thematic saturation, which we anticipate will occur with one additional focus group. Themes from all focus groups were identified and agreed upon by both investigators (U.D. and M.T.) and were verified by additional investigators (J.D., M.L, M.H., B.K.L, C.C., M.M.). Results: To date, we conducted five focus groups with a total of N=21 participants (median age 60 [range 41-88], 66.7% female, 71.4% non-Hispanic White, 14.3% Hispanic, 9.5% Asian, 4.8% Black/Hispanic). We identified the following themes and representative quotes: 1) Holistic approach:Participants wanted their oncologists to view their care from a holistic perspective, discussing their individual priorities and options that would accommodate their fitness routine and ability to work. “[I wish] if doctors can consider not just the physical choices, but also the mental and emotional choices as well, the holistic person.” - Participant 13 “There's zero chance I can go back to working in the type of career where other people rely on me for things. I can't keep things straight.” - Participant 16 2) Ideal treatment:An ideal treatment would limit impact on fatigue, cognitive function, and have minimal toxicity to preserve quality of life and an active lifestyle. “I would say something that has minimal impact on daily life would be ideal and something that would make you feel better.” - Participant 6 3) Shared decision-making: Participants wanted to be better informed about available treatment options and often utilized second opinions to inform their decisions. “It helped to get the second opinion versus not. It would've been a completely different set of events.” - Participant 17 4) Treatment burden:Financial impact and effort required by patients to receive care (e.g., travel, number of office visits, and duration of therapy) were key factors in patient decision-making. “Part of my quality of life went down because I had to fight with my insurance company consistently, and we pay a lot of money.” - Participant 11 “Really explain the time options and calendarize the treatment and be more specific about the amount of time that you're going to spend at the hospital and the process.” - Participant 20 5) Representation: Minority participants raised concerns about not knowing if the available treatment data pertained to them. “[My end-goal would be] having an understanding of how the treatment is going to be for minority people. Many times the treatments are tested, they are not tested for minorities.” - Participant 21 Conclusions: The patient perspective is critical for treatment decision-making and education. People living with FL expressed a desire for a holistic and individualized approach to treatment decision-making that incorporated their lifestyle, minimized side effects, and limited overall treatment burden. These focus groups identified emerging themes that warrant further investigation for survivors with FL.

Abstract Progression of disease within 24 months of initial immunochemotherapy (POD24) is a negative prognostic factor for patients with follicular lymphoma (FL). There is no standard treatment after POD24. Assembling an academic-based cohort from the Lymphoma Epidemiology of Outcomes Consortium for Real World Evidence, we evaluated patterns of care and outcomes for 220 patients with FL with POD24 and retained FL histology. Therapy after POD24 was heterogeneous, with no treatment category accounting for >25% of the total. Among patients initially treated with bendamustine-rituximab, rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) was the predominant second-line choice (48%). Among patients initially treated with R-CHOP, aggressive salvage therapy was the predominant second-line choice (38%). Overall response rate to therapy after POD24 was 64% (95% confidence interval [CI], 56-70); complete response rate was 39% (95% CI, 32-46). The median event-free survival for therapy after POD24 was 9.8 months (95% CI, 7.3-12.1); 5-year overall survival (OS) was 71% (95% CI, 65-78). OS was inferior for patients aged >70 years (hazard ratio [HR], 2.31; 95% CI, 1.27-4.20) and those with high-risk FL International Prognostic Index scores at diagnosis (HR, 2.10; 95% CI, 1.23-3.60). No treatment category stood out with more favorable results. Cause of death was predominantly lymphoma related. Patients with follicular histology at their POD24 event had a low cumulative incidence of transformation (1.1% at 5 years). Our study is among the largest cohorts describing contemporary patterns of care for patients with POD24, providing a focused data set useful for interpreting and designing prospective clinical trials in this population.

Abstract Recent introduction of 2 different lymphoma classifications has raised concerns about consistency in diagnosis, management, and clinical trial enrollment. Data from a large cohort reflecting real-world clinical practice suggest that differences between the classifications will affect <1% of non-Hodgkin lymphomas.

Abstract Underrepresentation of racial and ethnic subgroups in cancer clinical trials remains a persistent challenge. Restrictive clinical trial eligibility criteria have been shown to exacerbate this problem. We previously identified that up to 24% of patients treated with standard immunochemotherapy would have been excluded from recent first-line trials in diffuse large B-cell lymphoma (DLBCL) based on 5 laboratory-based criteria. These ineligible patients had worse clinical outcomes and increased deaths related to lymphoma progression, suggesting the potential exclusion of patients who could have benefited most from the novel therapies being evaluated. Using data from the prospectively enrolled Lymphoma Epidemiology Outcomes cohort study, with demographics broadly similar to the US patients diagnosed with lymphoma, we evaluated the impact of laboratory eligibility criteria from recent first-line DLBCL trials across various racial and ethnic backgrounds. There were significant differences in the baseline laboratory values by race/ethnicity with Black/African American (AA) patients having the lowest mean hemoglobin and highest creatinine clearance. Based on recent clinical trial eligibility criteria, AA and Hispanic patients had higher rates of laboratory-based ineligibility than non-Hispanic White patients. The largest gap in the clinical outcomes between eligible and noneligible patients was noted within AA patients with an overall survival hazard ratio based on POLARIX clinical trial criteria of 4.09 (95% confidence interval, 1.83-9.14). A thoughtful approach to the utility of each criterion and cutoffs for eligibility needs to be evaluated in the context of its differential impact across various racial/ethnic groups.