bluuebunny/crossref_metadata_2025 huggingface dataset:
Circulating tumor DNA (ctDNA) status and clinical outcomes in patients (pts) with previously untreated diffuse large B-cell lymphoma (DLBCL) in the POLARIX study.
Authors: Herrera Alex Francisco , Tracy Samuel , Sehn Laurie Helen , Jardin Fabrice , Lenz Georg , Trneny Marek , Salles Gilles A. , Flowers Christopher , Tilly Herve , Sharman Jeff Porter , Friedberg Jonathan W. , Balasubramanian Sandhya , Raghavan Vibha , Hirata Jamie H. , Lee Calvin , Jiang Yanwen , Morschhauser Franck
Published: June 2023

7523

Background: the POLARIX study, pts with previously untreated DLBCL were randomized to Pola-R-CHP or R-CHOP (NCT03274492; Tilly et al. 2022). We previously validated the prognostic value of ctDNA at baseline and after one cycle of therapy in POLARIX (Herrera et al. 2022); here, we evaluate the relationship between ctDNA clearance and PFS and OS. Methods: Pts were included if baseline and longitudinal ctDNA results were available. Plasma ctDNA was measured at baseline, Cycle (C) 5 Day (D) 1, and end of treatment (EOT), with the AVENIO NHL CAPP-Seq assay (Stokowski et al. 2022). ctDNA clearance was determined as previously described (Herrera et al. 2022). PFS and OS according to ctDNA status were reported as landmarked hazard ratios (HR) and 3-yr rates. HRs were adjusted for IPI score (>2), region, bulky disease (>7.5cm), age (>60 years), and cell of origin. Results: At baseline, 654 pts had ctDNA results; 494 (76%) and 519 (79%) pts were evaluable at C5D1 and EOT, respectively. Undetectable ctDNA (ctDNA−) was achieved by 57% (152/265) of Pola-R-CHP-treated pts and 59% (135/229) of R-CHOP-treated pts at C5D1 (p=0.79), and by 66% (172/262) of Pola-R-CHP-treated pts and 67% (172/257) of R-CHOP-treated pts at EOT (p=0.83). Achieving ctDNA− was prognostic for PFS and OS in each treatment arm at C5D1 and EOT (Table). Pts in the Pola-R-CHP arm who had complete response (CR) with PET-CT and ctDNA− at EOT had superior PFS and OS compared with pts with CR and detectable ctDNA (ctDNA+) at EOT (PFS HR 0.30, 95% confidence interval [CI]: 0.14–0.66; OS HR 0.20, 95% CI: 0.07–0.60). This was not observed with R-CHOP (PFS HR 0.74, 95% CI: 0.34–1.63; OS HR 1.11, 95% CI: 0.30–4.16). Among pts with CR and ctDNA− at EOT, pts treated with Pola-R-CHP had superior PFS vs R-CHOP (HR 0.41, 95% CI: 0.21–0.82); this was not observed with OS (HR 0.41, 95% CI: 0.14–1.18). There was no statistically significant difference in PFS between treatment arms in pts with CR and ctDNA+ at EOT (PFS HR 1.20, 95% CI: 0.49–2.83). Conclusions: Achieving ctDNA− at C5D1 and EOT was prognostic for longer survival. Although no difference was observed in the number of pts with ctDNA− at EOT between arms, pts achieving CR and ctDNA− at EOT had superior PFS in the Pola-R-CHP vs the R-CHOP arm, suggesting deeper molecular responses in pts treated with Pola-R-CHP beyond the detection sensitivity of the assay used in this analysis. Clinical trial information: NCT03274492 . [Table: see text]
High complete response rate with TNB-486 in relapsed/refractory follicular lymphoma: Interim results from an ongoing phase 1 study.
Authors: Nair Ranjit , Jacobs Ryan , Cho Seok-Goo , Devata Sumana , Gaballa Sameh , Yoon Dok Hyun , Stevens Don A. , Kim Jin Seok , Shah Nirav Niranjan , Brennan Denise Marie , Law Jason , Chen Rob , Forcina Alessandra , Buelow Ben , Hou Jing-Zhou
Published: June 2023

7524

Background: Follicular lymphoma (FL) is incurable with a relapsing/remitting pattern and decreasing progression-free survival (PFS) interval per recurrence. In the relapsed/refractory (R/R) setting, patients (pts) failing CAR T or CD20 bispecific T-cell engagers (TCE) have few options. TNB-486 is a novel bispecific CD19xCD3 TCE that induces T-cell–mediated cytotoxicity with reduced cytokine release via a low-affinity αCD3 moiety. We present interim data from a phase 1 dose-escalation study of TNB-486 (NCT04594642). Methods: Third-line+ R/R FL pts (grade [G] 1–3a) were enrolled (prior CD19 therapy allowed). Escalating fixed TNB-486 doses (0.03–2.4 mg) without priming were evaluated prior to implementing single (day [D] 1) and double priming doses (D1 & 8) prior to target dose (D15). TNB-486 was given IV every 2 weeks in 28-d cycles (C) for up to 2 y. Response was assessed with RECIL 2017 by central image review. Adverse events (AEs) and CRS/ICANS were graded by CTCAE v5.0 and 2019 ASTCT criteria. Results: As of Dec 31, 2022, 17 pts received TNB-486 at target doses 0.03–10 mg (median age 68 y [range 33–86]; 53% male; 65% stage III/IV; 25% CD20− disease; median prior lines of therapy [LOT] 3 [range 2–9]). Prior therapies included αCD20 Ab (100%), alkylator (76%), IMiD (47%), CD20 TCE (12%), CD19 CAR T (12%), and ASCT (6%); 53% progressed or started 2nd LOT within 24 mo of initiating 1st LOT (POD24). Median time on study was 7 mo (range 1–22). Eleven pts were response evaluable for efficacy at target doses ≥2.4 mg. Objective response rate (ORR) and complete response (CR) rate were 91% (Table). ORR/CR for pts with CD20− disease, prior CD20 TCE, and POD24 was 100%. One pt progressed at C6 with preserved CD19 expression; all others remain in remission to date. The 6-mo PFS rate was 91%. No G3+ CRS occurred (59% G1, 12% G2). Neurologic events consistent with ICANS were reported in 24%, all G1–2 except 1 with a G3 event (confusion). All CRS/NT were transient, resolving in a median of 1.5 d (range 1–5). G3+ treatment-related AEs in >10% of pts included decreased lymphocytes (35%) and neutropenia (12%). No treatment-related deaths or AEs leading to discontinuation occurred (1 pt died and 1 discontinued due to COVID-19). One pt received double step-up priming dosing to date with no CRS/NT. Conclusions: TNB-486 induces high complete remission rates during early phase dose escalation. With limited follow-up, responses appear durable in heavily pretreated FL pts, with a manageable safety profile. Dose escalation is ongoing to identify the RP2D. Clinical trial information: NCT04594642 . [Table: see text]
Rates of cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) from Center for International Blood and Marrow Transplant Research (CIBMTR) data on US subjects (SUBJ) with lymphoma following chimeric antigen receptor T cell therapy (CAR-T).
Authors: Frigault Matthew J. , Amoloja Theresa , Burke Lea Micaletti , Morariu-Zamfir Rodica , Bhatt Valkal , Bibeau Kristen , Tang Xiao Ying , Moskop Amy , Maziarz Richard T. , DiPersio John F.
Published: June 2023

7528

Background: The engineered T-cell products axicabtagene ciloleucel (axi-cel) and brexucabtagene autoleucel (brexu-cel) are FDA approved for relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL), respectively. This study investigated real-world rates of CRS and ICANS following CAR-T. Methods: This study analyzed CIBMTR data of US SUBJ receiving axi-cel or brexu-cel for any indication from Oct 2020–Dec 2021 with ≥1 follow-up visit. CRS and ICANS were graded per American Society for Transplantation and Cellular Therapy consensus guidelines. Results: 927 SUBJ (median age, 63 y; men, 65%) from 87 centers were analyzed. Most received axi-cel (76%), 83% of whom had DLBCL or transformed follicular lymphoma (tFL); 24% received brexu-cel (MCL). Most SUBJ had Ann Arbor stage III/IV (63%), no active central nervous system disease (84%), and refractory disease at CAR-T infusion (66%). Among all 589 SUBJ with DLBCL/tFL who received axi-cel, 54% achieved complete response, 17% partial response, and 6% stable disease. 89/715 SUBJ with available data received treatment for CRS prevention, mostly tocilizumab alone (80% [71/89]) or in combination (3% [3/89]). Overall, 766 SUBJ (83%) developed CRS (grade ≥3, 64 [8%]; Table). Of the 89 SUBJ who received CRS prevention treatment, 78% developed CRS, with 3% (3/89) having grade ≥3. 77% of SUBJ with CRS received CRS treatment, 97% of whom received tocilizumab (alone or in combination [eg, with corticosteroids]). Most (64%) SUBJ with grade 1 CRS received treatment, 63% of whom received tocilizumab alone. ICANS occurred in 424/876 SUBJ with ICANS data (48%; Table), of whom 205 (48%) had grade ≥3. ICANS treatment was reported and administered to 86% of SUBJ with ICANS, 92% of whom received corticosteroids. Conclusions: CRS and ICANS incidence rates were consistent with previously published literature and highlight potential burdens of CAR-T. In addition, the treatment landscape for CRS is changing; SUBJ with grade 1 CRS often received treatment. These data will inform the design of future studies aimed at preventing and treating CAR-T toxicities. [Table: see text]
Fixed-duration ibrutinib + venetoclax for first-line treatment of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): 4-y follow-up from the FD cohort of the phase 2 CAPTIVATE study.
Authors: Barr Paul M. , Allan John N. , Siddiqi Tanya , Wierda William G. , Tam Constantine Si Lun , Moreno Carolina D. , Tedeschi Alessandra , Szafer-Glusman Edith , Zhou Cathy , Abbazio Chris , Dean James P. , Szoke Anita , Ghia Paolo
Published: June 2023

7535

Background: CAPTIVATE (PCYC-1142) is a multicenter phase 2 study of first-line ibrutinib (I) + venetoclax (V) in CLL/SLL. Follow-up results from the fixed duration (FD) cohort showed 3-y PFS rate of 88% overall and rates ≥80% in patients (pts) with high-risk features (Wierda, ASCO 2022). Here we present updated results from the FD cohort with 4-y follow-up. Methods: Pts aged ≤70 y with previously untreated CLL/SLL received 3 cycles of I then 12 cycles of I+V (I 420 mg/d orally; V ramp-up to 400 mg/d orally). Responses were investigator assessed per iwCLL 2008 criteria. Undetectable minimal residual disease (uMRD; <10‒4) was assessed by 8-color flow cytometry. Results: 159 pts were enrolled, including pts with high-risk features of unmutated IGHV (uIGHV) (56%) or del(17p) and/or TP53 mutation (17%). Median time on study was 50 mo (range 1‒53). At 4 y of follow-up, the best CR rate was 58% and ORR was unchanged at 96%. At 4 y, PFS rate was 79% (95% CI 71‒84) and OS rate was 98% (95% CI 94–99). 4 y PFS rates were numerically lower in pts with uIGHV (73%) or del(17p) and/or TP53 mutation (63%), while OS rates remained consistently high (Table). 4 y PFS rates by MRD status 3 mo after stopping treatment (EOT+3) were significantly higher overall in pts with uMRD vs detectable MRD (dMRD) in PB (90% vs. 66%, Table); this difference was minimal at 24 mo (100% vs 91%). Median TTNT was not reached overall (range 1–53 mo); the 4 y rate of freedom from next treatment was 84% (95% CI 77–89). Second malignancies continue to be collected off treatment; 1 AE of prostate cancer occurred during this y of follow-up. To date, 19 pts with PD after completing fixed duration I+V in either the FD cohort or MRD cohort placebo arm initiated retreatment with I. Responses in 17 pts with available data were 1 CR, 13 PR, and 1 each PR with lymphocytosis, SD, and PD. Median time on retreatment was 11 mo (range 0–39). The most common AEs (≥10%) with retreatment were diarrhea (n=3), COVID-19 (n=3), and anemia (n=2). In addition, 4 pts have started I+V retreatment to date. Conclusions: Results of the CAPTIVATE study support I+V as an all-oral, once-daily fixed-duration regimen for previously untreated pts with CLL/SLL. With 4 y follow-up, fixed-duration I+V continues to provide deep, durable remissions with clinically meaningful PFS and time off treatment, including in pts with high-risk disease features. New safety findings off-treatment were expectedly negligible, highlighting the benefits of a fixed duration regimen. Promising responses were observed upon retreatment with I in progressing pts. Clinical trial information: NCT02910583 . [Table: see text]
Real-world outcomes by race in patients (pts) with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): Final analysis results from the informCLL registry.
Authors: Barrientos Jacqueline Claudia , Sharman Jeff Porter , Gutierrez Meghan E. , Wu Linda , Qureshi Zaina P. , Raz Anat , Girardi Vincent , Naganuma Maoko , Ghosh Nilanjan
Published: June 2023

7536

Background: informCLL is a large, US-based, prospective, observational registry of pts with CLL/SLL initiating treatment (tx) in the era after approval of ibrutinib (Ibr). Here, we report real-world tx patterns and outcomes by race and line of therapy (LOT) from the final analysis of informCLL. Methods: Pts with CLL/SLL who initiated FDA-approved tx were enrolled between 10/2015 and 6/2019. Baseline characteristics, tx patterns, time to next tx (TTNT), OS, and safety are summarized by race (focus on Black and White pts) and LOT (first-line [1L] or relapsed/refractory [R/R], with focus on 1L). Results: Of 1459 eligible pts enrolled, 105 were Black (1L, n=58; R/R, n=47), 1323 were White (1L, n=779; R/R, n=544), and 31 were of other races (Asian [n=6], Native American [n=4], other/not reported [n=21]). Relative to White pts, 1L-treated Black pts were younger (median age 65 vs 70 y) and had worse performance status (ECOG status ≥1: 59% vs 50%), more advanced disease (Rai stage III-IV: 55% vs 46%), shorter time from diagnosis to 1L tx (median 7 vs 19 mo), and lower rates of del(17p) among tested pts (6% vs 13%). Across race, Ibr was the most common 1L tx (Black, n=29 [50%]; White, n=346 [44%]) followed by CIT (Black, n=25 [43%]; White, n=331 [42%]). With median follow-up of approximately 32 mo in 1L-treated pts, the estimated rate of freedom from next-line therapy at 36 mo was similar between Black and White pts across all-treated pts and among Ibr-treated subgroups (Table). Estimated 36-mo OS rates in all-treated pts were also similar by race, with a high OS rate observed among Ibr-treated Black pts (97% at 36 mo). In multivariate analyses (MVA) in 1L-treated pts, male gender, poorer ECOG status, and increased comorbidity burden were independent predictors of decreased OS while race was not associated with OS. In 1L Ibr-treated pts, the only factor associated with decreased OS in MVA was longer time from diagnosis to 1L tx. Rates of serious AEs and AEs leading to tx discontinuation appeared similar across race (Table). Conclusions: Although historical retrospective studies from the pre-novel agent era have shown poorer clinical outcomes among Black pts with CLL relative to non-Black pts, results from informCLL show similar or potentially improved outcomes, including OS, among 1L Ibr-treated Black pts relative to White pts. These results suggest that access to novel agents such as Ibr may in part overcome historical disparities in clinical outcomes by race in pts with CLL. Clinical trial information: NCT02582879 . [Table: see text]
A matching-adjusted indirect comparison (MAIC) of the efficacy and safety of acalabrutinib (acala) versus zanubrutinib (zanu) in relapsed or refractory chronic lymphocytic leukemia (RR CLL).
Authors: Kittai Adam , Skarbnik Alan , Miranda Miguel , Yong Alan SM , Roos Jack , Hettle Robert , Palazuelos-Munoz Sarah , Shetty Vikram , Ghia Paolo
Published: June 2023

7540

Background: The BTKi ibrutinib is the standard of care in RR CLL and was compared in head-to-head randomized clinical trials (RCTs) with second-generation BTKis: acala in ELEVATE-RR and zanu in ALPINE. However, major differences in these RCT's populations prevents comparison of acala and zanu. Acala was also assessed in the ASCEND RCT, which had a similar population to ALPINE but a different comparator. Thus, we used unanchored MAIC to compare the efficacy and safety of acala vs zanu using individual patient data (IPD) from ASCEND and published aggregate data from ALPINE. Methods: In the unanchored MAIC, acala IPD from ASCEND were weighted to match zanu baseline data from ALPINE. This reduced between-study differences in variables that were prognostic/effect-modifying of progression-free survival (PFS) in an exploratory multivariate cox regression analysis of ASCEND. These included sex, ECOG PS, bulky disease, prior chemoimmunotherapy, del(11q), del(17p), TP53 without del(17p), IGHV status, region, age, prior lines of therapy and Rai stage. An efficacy analysis assessed investigator-assessed PFS (INV PFS) in randomized patients with baseline data (acala, n = 149; zanu, n = 327). Pseudo IPD for INV PFS for zanu were obtained from Kaplan-Meier curves. A safety analysis assessed odds ratios (ORs) of AEs in treated patients with baseline data (acala, n = 148; zanu, n = 324). To allow comparison of the incidence of AEs, an artificial data cut-off (Feb 21, 2020) was imposed for acala to match the zanu median treatment exposure (both 28.4 months). Results: After matching, the effective sample size of acala was 99 (66.6%; 65% male; median age 66 years). 12- and 24-month INV PFS are shown below. The MAIC hazard ratio (HR) for INV PFS is similar for acala vs zanu (HR 0.90, 95% CI 0.60–1.36). The risk of having grade ≥ 3 AE (OR 0.66, 95% CI 0.41–1.05), atrial fibrillation (AF; OR 1.32, 95% CI 0.56–3.08), grade ≥ 3 AF/atrial flutter (OR 0.60, 95% CI 0.12–2.89), grade ≥ 3 hemorrhage (OR 0.61, 95% CI 0.19–2.03) or an AE leading to discontinuation (OR 1.14, 95% CI 0.61–2.13) was similar with acala vs zanu. The risk of having a serious AE (OR 0.61, 95% CI 0.39–0.97), hypertension (any grade: OR 0.18, 95% CI 0.09–0.37; grade ≥ 3: OR 0.22, 95% CI 0.09–0.54), any grade hemorrhage (OR 0.54, 95% CI 0.34–0.87) or an AE leading to dose reduction (OR 0.30, 95% CI 0.14–0.67) was lower with acala vs zanu. Conclusions: Acala and zanu have a similar efficacy in patients with RR CLL, while acala has a lower risk of grade ≥ 3 hemorrhage, any grade and grade ≥ 3 hypertension and dose reduction due to AEs vs zanu. Limitations of MAIC analyses mean the results should be viewed as hypothesis-generating. [Table: see text]
Utility of pharmacogenomic testing in predicting intolerance to BTK inhibitors.
Authors: Basher Fahmin , Scobie Micaela R , Kelley Michael J. , Voora Deepak , Friedman Daphne Ruth
Published: June 2023

7541

Background: Oral inhibitors of Bruton’s tyrosine kinase (BTKi) are used for a number of B-cell malignancies, including chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL) and lymphoplasmacytic lymphoma (LPL). Real-world data has demonstrated that BTKi discontinuation is commonly due to intolerance, but contributing factors are not fully understood. Prior work suggests that cytochrome P450 (CYP) polymorphisms may increase the risk of targeted therapy discontinuation in CLL. We utilized pharmacogenomic (PGx) testing in Veterans treated with BTKi to evaluate the potential contribution of CYP polymorphisms to intolerance and responses to BTKi. Methods: We identified Veterans receiving care through the Veterans Administration (VA) who were prescribed a BTKi and underwent testing through the Pharmacogenomic Testing for Veterans (PHASER) program, currently offered at 22 VA facilities. We analyzed factors including time on BTKi therapy, reasons for discontinuation, and use of concomitant medications known to strongly inhibit CYP. Event-free survival (EFS) was defined as time from BTKi initiation to discontinuation. Results: Eighty-nine Veterans treated with BTKi who had PGx testing were identified, of which 97% (86) were male and 85% (76) were diagnosed with CLL. Other diagnoses included LPL (4), MCL (3), and MZL (3). Seventy-seven patients (pts) were treated with ibrutinib, nine with acalabrutinib and three with zanubrutinib. Three pts had poor metabolizer genotype (PMG) for CYP2C19 and 25 pts received strong CYP2C19 inhibitors (inh). Thirty-two pts had PMG for CYP2D6, and 12 pts received strong CYP2D6 inh. With a median follow up time of 38.9 months, 25 pts (28%) permanently discontinued due to intolerance and 10 pts (11%) progressed on BTKi therapy. Another 25 pts temporarily discontinued therapy. Median duration of BTKi therapy was 11.0 months for pts discontinuing for intolerance, 23.2 months for pts discontinuing for progression, and 38.5 months for pts not discontinuing therapy. Reasons for intolerance included arrhythmia, bleeding, and infections. EFS due to intolerance or progression was not statistically different between pts who were either CYP2C19 PMG or who received strong CYP2C19 inh, compared to all other pts. Interestingly, EFS due to intolerance alone was statistically different comparing these groups (p = 0.014, median 49.4m vs NR), but EFS due to progression was not (p = 0.76, median 79.6m vs NR). EFS was not significantly different comparing pts who were either receiving strong CYP2D6 inh or were PM to those who were not. Conclusions: We found that Veterans who were treated with BTKi and who either took concomitant strong CYP2C19 inh or had a CYP2C19 PMG were more likely to have intolerable side effects of BTKi therapy leading to discontinuation. Our results suggest that evaluating polypharmacy and PGx factors should be considered when prescribing BTKi.
Safety and efficacy of ABR in pts with TN or R/R MCL: Ph Ib trial.
Authors: Phillips Tycel Jovelle , Wang Michael , Robak Tadeusz , Gallinson David , Stevens Don A. , Patel Krish , Ramadan Safaa , Wun Chuan-Chuan , Jurczak Wojciech , Smith Stephen Douglas
Published: June 2023

7546

Background: Acalabrutinib (A) is a next-generation Bruton tyrosine kinase inhibitor approved for relapsed/refractory (R/R) mantle cell lymphoma (MCL). Bendamustine (B) + rituximab (R) is used for treatment-naive (TN) and R/R MCL. We present updated data on safety and efficacy of ABR in patients (pts) with TN or R/R MCL. Methods: Eligible adults received ABR in this phase 1b study (NCT02717624) as follows: ABR for 6 28-d cycles, maintenance A+R for up to 2 y (TN cohort responders), then oral A continuously until progressive disease (PD) or treatment discontinuation due to toxicity (both cohorts). The primary endpoint was safety. Secondary endpoints were overall response rate (ORR), progression-free survival (PFS), and duration of response (DOR), all per Lugano. Results: Overall, 38 pts were enrolled (TN, n=18; R/R, n=20) with median age 66 y (range, 47–86). Baseline characteristics were (TN and R/R cohorts, respectively): stage IV disease in 88.9% and 95.0%, high-risk simplified MIPI score in 11.1% and 15.0%, bulky disease >5 cm in 16.7% and 30.0% or ≥10 cm in 5.6% and 10.0%, and blastoid morphology in 5.6% and 15.0%; R/R pts had a median of 2 prior lines of therapy. As of the data cutoff date (6/15/22), 6 (33.3%) TN pts and 4 (20.0%) R/R pts were receiving A monotherapy (Table). Most common any-grade AEs were nausea (n=14, 77.8%; TN) and neutropenia (n=11, 55.0%; R/R). Grade 3–4 AEs occurred in 13 (72.2%) TN pts and 17 (85.0%) R/R pts, most commonly neutropenia in both cohorts (n=7, 38.9% [TN]; n=10, 50.0% [R/R]). Serious AEs occurred in 11 (61.1%) TN pts and 13 (65.0%) R/R pts. There were no reports of ventricular tachyarrhythmia. Grade 3 atrial fibrillation occurred in 1 pt outside the safety reporting period and was not related to study treatment. Grade ≥3 major hemorrhage was reported in 2 (11.1%) TN pts and 3 (15.0%) R/R pts. Grade ≥3 hypertension was reported in 3 (16.7%) TN pts and 2 (10.0%) R/R pts. Five TN pts died (AE: pneumonitis, n=1; unknown, n=4) and 6 R/R pts died (AE: COVID and cerebrospinal meningitis, n=2; PD, n=2; unknown, n=2). ORR was 94.4% (n=17) in the TN cohort and 85.0% (n=17) in the R/R cohort, with CR rates of 77.8% (n=14) and 70.0% (n=14), respectively. Median DOR was not estimable (NE) in the TN cohort and 43.5 mo in the R/R cohort. Median PFS and overall survival were NE in the TN cohort (median follow-up 47.6 mo) and 28.6 mo and NE, respectively, in the R/R cohort (median follow-up 20.4 mo). Conclusions: Triple-combination ABR was tolerable and effective in pts with TN or R/R MCL. Clinical trial information: NCT02717624 . [Table: see text]
Real-world outcomes with novel therapies in R/R DLBCL.
Authors: Crombie Jennifer Leigh , Jun Monika P. , Wang Tongsheng , Mutebi Alex , Wang Anthony , Chibber Anindit , Kamalakar Rajesh , Ukropec Jon , Blædel Julie , Kalsekar Anupama
Published: June 2023

7552

Background: Outcomes have historically been poor for patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Despite an increase in approved R/R DLBCL treatment options, clinical outcomes of these therapies remain less certain. Novel treatments for R/R DLBCL patients include chimeric antigen receptor T-cell (CAR T) therapy, polatuzumab vedotin plus bendamustine and rituximab (pola-BR), tafasitamab plus lenalidomide (tafa-len), loncastuximab (lonca), and selinexor. The objective of this study was to examine real-world outcomes of these novel therapies. Methods: US patient data from the COTA electronic health records database (2010–2021) were used for this retrospective study. Patients had a diagnosis of DLBCL after 1/1/2010, with ≥1 prior line of systemic antineoplastic therapy (including an anti-CD20 antibody), and treatment with any of these novel therapies. Patients receiving variations of pola-BR or tafa-len regimens were included. Outcomes included overall response rate (ORR), complete response (CR) rate, median progression-free survival (mPFS), and median overall survival (mOS). Outcomes were also analyzed for those treated with any novel therapy following prior CAR T exposure. Results: A total of 175 R/R DLBCL patients were included (median age 63 y, 60.6% male, median of 2 prior therapies); 29.1% had an international prognostic index score ≥3, 61.7% had stage III/IV disease, and 65.7% had primary refractory disease. A total of 73, 69, and 27 patients were treated with CAR T, pola-BR, and tafa-len regimens, respectively. Only 6 patients were treated with lonca and no patients received selinexor. Among 169 patients treated in the 2L+ setting with tafa-len, pola-BR, and CAR T, the CR rate was 11.1%, 18.8%, and 52.1%, respectively (Table). A total of 112 patients were treated in the 3L+ setting with CR rate of 10.0%, 13.5%, and 41.8%, for tafa-len, pola-BR, and CAR T, respectively. Outcomes in the 18% of patients treated with any novel agent following CAR T exposure were ORR of 19.1%, CR of 4.8%, and mPFS and mOS of 1.4 mo and 2.3 mo, respectively. Conclusions: Outcomes of pola-BR and tafa-len regimens in the 2L+ and 3L+ R/R DLBCL setting remain suboptimal, with worse outcomes as patients advance through lines of therapy. Outcomes are particularly poor when these agents are used following CAR T therapy. [Table: see text]
Phase II trial of split-dose R-CHOP for older patients with diffuse large B-cell lymphoma (DLBCL).
Authors: Shah Nirav Niranjan , Szabo Aniko , Rajguru Saurabh , Devata Sumana , Howard Mitch , Pereira Deepa , Endres Mariah , Longo Walter L. , Hamadani Mehdi , Fenske Timothy S. , Fletcher Christopher David
Published: June 2023

7554

Background: Management of elderly DLBCL is limited by age associated comorbid conditions and decreased tolerance of chemotherapy regimens. Many elderly or unfit/frail patients (pts) with DLBCL receive either non-anthracycline based treatment (tx) or attenuated regimens such as Rituximab (R)-miniCHOP which is ~50% dose reduction from standard R-CHOP-21. Split-dose (SD) R-CHOP is an alternative approach where pts receive CHOP at a 50% dose reduction on Days 1 and 15 of each 28-day cycle with full dose Rituximab on Day 1 for 6 cycles. The cumulative dose of SD R-CHOP delivered over each 28 day cycle is equivalent in dose intensity to one cycle of standard R-CHOP-21. Methods: This is a Phase II, prospective, open label study conducted through the Wisconsin Oncology Network and included two academic centers (NCT03943901). Older pts aged≥75 years or 70-74 years plus elevated cumulative illness rating scale for geriatrics score with untreated de-novo or transformed Stage IIX-IV DLBCL were eligible. Treatment consisted of two months (4 doses) of SD R-CHOP with growth factor support followed by interim response assessment with PET/CT and peripheral blood cell-free clonoSEQ minimal residual testing (MRD). Pts with interim PET/CT score of Deauville 1-3 and MRD negativity were offered abbreviated therapy with two additional months of SD-R-CHOP. All others completed 6 cycles. The primary endpoint was end of tx (EOT) complete response (CR) rate. We utilized a Simon 2-stage design with interim analysis requiring at least 8 EOT CR in the first 16 pts (Stage I) to proceed to stage II. Results: To date, 14 pts have completed tx. The median age was 81 years (73-88) and 57% (n = 8) were male. Most pts had stage 4 disease (n = 8, 57%). 8 of 14 pts were interim PET/CT negative and 8 of 12 MRD evaluable pts were interim MRD negative. 10/14 (71%) pts achieved EOT CR exceeding our minimal threshold to continue the study early. The remaining 4 pts had progressive disease (PD) either during tx or at EOT evaluation. 6 pts were both interim MRD and PET negative; 5 de-escalated to the abbreviated arm with all achieving CR with no relapses to date. 7 pts (50%) had Grade 3+ non-hematologic toxicities and 4 pts (29%) had Grade 3-4 neutropenia. There were 2 deaths, one from COVID-19 with concurrent PD and the other from PD. Median PFS or OS have not been reached with a median follow-up of 13 months for surviving pts. Conclusions: SD-R-CHOP offers older pts with DLBCL equivalent dose intensity as R-CHOP-21 through a fractionated dosing schedule improving tolerability. Prespecified interim efficacy endpoint was met early with 10/14 pts with EOT CR. Interim stratification by MRD and PET/CT allowed de-escalation of tx in early responding pts without compromising efficacy. Clinical trial information: NCT03943901 . [Table: see text]
Long-term efficacy and safety of pembrolizumab with R-CHOP as first-line therapy for DLBCL.
Authors: Ho Carrie , Fromm Jonathan R. , Fang Min , Till Brian G. , Shadman Mazyar , Cowan Andrew , Lynch Ryan C. , Wu Vicky , Voutsinas Jenna M. , Rasmussen Heather A. , Blue Katharine , Ujjani Chaitra Shankar , Shustov Andrei R. , Cassaday Ryan Daniel , Gopal Ajay K. , Smith Stephen Douglas
Published: June 2023

7561

Background: Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) represents the historical 1st line treatment standard for DLBCL but fails to cure about 1/3 of patients. While generally ineffective in relapsed DLBCL-NOS, checkpoint inhibitors may have greater promise in untreated, immunocompetent patients. We previously reported safety and early efficacy of pembrolizumab plus RCHOP, noting objective responses in 90% of patients (CR 77%) and a 2-year progression-free survival (PFS) of 83%. We now report 5 year follow up of our study. Methods: Patients age > 18 with untreated DLBCL or grade 3b follicular lymphoma, intended to receive 6 cycles of R-CHOP, were eligible. Pembrolizumab 200 mg IV with R-CHOP was given in 21-day cycles for 6 cycles. For this updated analysis, progression and survival events, and immune-related toxicities, are reported. Additionally, prognostic factors including tumor PD-L1 expression (Qualtek/Merck) were re-analyzed. Results: 30 patients were treated (13/30 with IPI 3-5). Median follow up is now 4.8 years (95% CI, 4.5-5.4). Since our initial report (Smith BJH 2019) we have observed 1 additional relapse (alive after CAR-T therapy) and 2 deaths in remission (1 urothelial carcinoma, 1 respiratory failure in the setting of progressive ILD). 5-year PFS is 71% (CI, 54-94%) and 5-year overall survival 83% (CI, 71-98%). During the study period and at long term follow up, there were 8 total immune-related adverse events (IRAEs) among 7 patients (23%) (Table). Four were treatment-emergent AE (occurred within 90 days of completing treatment): grade 1 hyperthyroidism, grade 2 hyperthyroidism, grade 3 pneumonitis, and grade 3 rash. There were 4 late IRAEs: colitis, paraneoplastic pemphigus, rheumatoid arthritis, and Graves’ disease, occurring at 3, 5, 8, and 46 months after completing treatment, respectively. PD-L1 tumor expression was documented in 19 of 23 (83%) tested patients. At long-term follow up, none of the 19 patients who had any PD-L1 expression have relapsed. Two out of the 4 patients with no PD-L1 expression have relapsed. On univariate analysis, PD-L1 H-score >0 (p<0.0001) was associated with improved PFS. Conclusions: At 5 year follow-up, pembrolizumab plus R-CHOP has led to durable responses in most patients with the best outcomes in PDL1-expressing disease. Furthermore, the safety profile was manageable, with a low rate of grade 3 or higher IRAEs (10%) and no consistent pattern of late events. These data support ongoing strategies incorporating PD-1/PDL-1 inhibitors in 1st line DLBCL therapy and confirmation of predictive biomarkers including tumor PD-L1 expression. Clinical trial information: NCT02541565 . [Table: see text]
A multi-institutional prospective cohort study of minimal residual disease in peripheral T-cell lymphoma: Impact of autologous stem cell transplant.
Authors: Foley Nicole C. , Russler-Germain David , Watkins Marcus , Jacobsen Eric D. , Moskowitz Alison J. , Cashen Amanda F. , Fehniger Todd A. , Kahl Brad S. , Ghobadi Armin , Reagan Beth , Fischer Anne , Wan Fei , Jacobsen Austin , Elias Karina , Holman Matt , Hill Natalie , Gordon Skyler , Huang Ying , Horwitz Steven M. , Mehta-Shah Neha
Published: June 2023

7563

Background: Roughly 80% of pts with peripheral T-cell lymphomas (PTCL) respond to CHOP-based therapy but 5-yr survival ranges between 20-40%. The high relapse rate after complete response (CR) suggests more sensitive response assessment, such as minimal residual disease (MRD) testing, could have prognostic or predictive value. Next generation sequencing (NGS) of the T-cell receptor (TCR) can detect a known TCR clonotype at 10-5. In a prospective study, we evaluated the utility of MRD testing via TCR NGS in PTCL (NCT03297697). Here we report results for pts pre- and post-autologous stem cell transplant (ASCT). Methods: This investigator-initiated, multi-institutional, prospective cohort study assessed MRD testing by TCR NGS in PTCL. Pts with previously untreated PTCL not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AITL), anaplastic large cell lymphoma (ALCL), PTCL with T-follicular helper (TFH) phenotype, or monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) treated with anthracycline-based curative-intent therapy were eligible. Baseline TCR (TRG or TRB) clonotypes were established from diagnostic tissue or peripheral blood if tissue was not available. TCR clonality was determined positive via the LymphoTrack TRG/TRB Assays – MiSeq (Invivoscribe, San Diego, CA) when top % reads were ≥2.5% and ≥2x above background. Samples were obtained at diagnosis (pre-treatment), following induction therapy (EOT/pre-ASCT), and serially post-ASCT. Results: Of 43 enrolled pts, 19 underwent consolidative ASCT, of which 10 had post-ASCT samples available for MRD testing (Table). Median age at ASCT was 62 years (range: 38-77). Baseline TCR clonotypes were identified in 10/10 pts. At pre-ASCT evaluation, 7/10 pts had detectable TCR MRD (‘pos’) and 3/10 pts had TCR MRD below the level of detection (‘neg‘). Of the 3 MRD neg pts pre-ASCT, 2 had CR and 1 had PR by PET-CT. All 7 TCR MRD pos pts pre-ASCT had CR by PET-CT. Of 7 MRD pos pts pre-ASCT, 6 remained MRD pos and 1 became MRD neg post-ASCT. Of the 4 MRD neg pts post-ASCT, none have relapsed at 52, 31, 34, and 31 mo post-ASCT. Of 7 MRD pos pts pre-ASCT, 3 have relapsed following ASCT (at 3, 9, and 29 mo post-ASCT). Conclusions: In this cohort of patients with PTCL receiving consolidative ASCT in CR1, all 4 pts with negative TCR MRD post-ASCT remain in remission at median follow up of 32.5 mo post-ASCT. The negative predictive value of TCR NGS MRD post-ASCT should be further evaluated. Clinical trial information: NCT03297697 . [Table: see text]
Racial and ethnic disparities in risk of second primary malignancies among diffuse large B-cell lymphoma survivors.
Authors: Advani Pragati Gole , Attwood Kristopher , Herr Megan , Ba Aqeel Sheeba Habeeb , Torka Pallawi
Published: June 2023

7567

Background: Previous studies have shown an increased risk of second primary malignancies (SPMs) among diffuse large B-cell lymphoma (DLBCL) survivors; however, this has not been comprehensively examined by race/ethnicity. We utilized a large population-based database to examine disparities in SPM risk by race/ethnicity. Methods: From 17 United States population-based Surveillance, Epidemiology and End Results (SEER) program cancer registry areas, we identified 57,262 ≥12-month first-primary DLBCL survivors diagnosed between 2000-2019. Standardized incidence ratios (SIRs) and accompanying 95% confidence intervals (CIs) quantified SPM risk by race/ethnicity (non-Hispanic White, Black, Asian/Pacific Islander [API] and Hispanic), compared with the general population. Results: Overall, we observed 4,719 SPMs after DLBCL representing a 1.2-fold significantly increased risk (95% Confidence Interval [CI] = 1.16-1.23) compared to the general population and an excess of 23 cases per 10,000 person-years. SIRs for all second cancers combined varied significantly by race/ethnicity with APIs and Hispanics presenting higher overall SPM risk [SIRAPI: 1.42 (CI = 1.27-1.59), and SIRHispanic: 1.31 (CI = 1.19-1.43)] compared to the White or Black patients [SIRwhite: 1.17 (CI = 1.13-1.21), SIRBlack: 1.16 (CI = 1.03-1.30)] (p-heterogeneity < 0.001). Heterogeneity by race/ethnicity in SIRs was even more pronounced in DLBCL survivors diagnosed at a younger age, those who were ≥5 years into their survivorship, those who had received chemotherapy, or those who had received no radiation as their initial treatment. Although SIRs for SPM was significantly higher for advanced stage DLBCL survivors (compared to those with a localized/regional disease), heterogeneity by race/ethnicity in SPM risk was significant regardless of the stage. Results from site specific analyses reported significantly higher overall SIRs for second hematological malignancies compared to solid cancers [SIRhemat: 3.52 (CI = 3.22-3.85), and SIRsolid: 1.08 (CI = 1.04-1.11)]. Patterns by race/ethnicity also varied significantly by second cancer type, particularly for second primary anal cancer, Hodgkin’s lymphoma (HL), and Acute Non-Lymphocytic Leukemia (ANLL) (p < 0.001 for each). Strikingly elevated SPM risks (SIRs > 10) were observed for second primary anal cancer, HL and ANLL among the Black patients, and HL among the APIs and Hispanic DLBCL survivors, compared to the white patients. Conclusions: Using a large-scale population-based data, we observed substantial disparities in SPM risk by race/ethnicity, with patients belonging to minority groups experiencing higher risks. SPMs have emerged as an important challenge for DLBCL survivors, therefore, further research to understand drivers of the observed race/ethnicity heterogeneity is warranted.
Uncertainty and coping in patients with newly diagnosed indolent non-Hodgkin’s lymphoma (iNHL).
Authors: Newcomb Richard , Johnson Patrick Connor , Yang Daniel , Amonoo Hermioni L. , Dhawale Tejaswini More , Chen Yi-Bin Albert , El-Jawahri Areej
Published: June 2023

7568

Background: iNHLs are a heterogenous group of incurable diseases with prolonged illness courses requiring intermittent periods of surveillance and treatment. Due to illness uncertainty, patients with iNHL struggle with immense psychological distress. Yet, studies exploring coping, prognostic uncertainty and distress in this population are limited. Methods: We conducted a cross sectional study of adults (age ≥ 18) newly diagnosed with iNHL at a single academic center. We enrolled consecutive patients who were diagnosed ≤ 3 months prior to study enrollment. At baseline, we collected patient reported outcomes to assess QOL (Functional Assessment of Cancer Therapy), psychological symptoms (Hospital Anxiety and Depression Scale), prognostic understanding (Prognostic Awareness Impact Scale), and coping (Brief COPE). We categorized coping as approach-oriented (active coping, use of emotional support, positive reframing, acceptance) and avoidant (behavioral disengagement, denial, and self-blame). We used median split to differentiate between low and high utilizers of approach or avoidant coping. Results: We enrolled 70.6% (48/68) of eligible patients newly diagnosed with iNHL (mean age 66.8 yrs; 39.6% chronic lymphocytic leukemia/ lymphoma; 33.3% follicular lymphoma). At baseline, nearly one-third (31.2%) experience clinically significant symptoms of anxiety and depression. 45.8% of patients identified prognostic uncertainty as the “the most stressful part of being a patient,” and 31.2% reported having “difficulty letting go of thoughts about their prognosis.” Notably, patients had significant misperceptions about their prognosis with incurable iNHL, as 47.9% reporting that a cure was at least ‘somewhat’ likely. Patients with iNHL most often used acceptance (56.3%), denial (47.9%), and emotional support (47.9%) as coping strategies. Patients who were high utilizers of multiple approach-oriented coping strategies experienced fewer anxiety (B = -2.66, p = 0.01) and depression (B = -1.73, p = 0.02) symptoms and improved QOL (B = 9.43, p = 0.001). Patients who highly utilized any avoidant-oriented coping strategies experienced increased anxiety symptoms (B = 2.16, p = 0.05), but no difference in depression symptoms or QOL. Conclusions: Patients with iNHL report immense prognostic uncertainty and psychological distress. Use of multiple approach oriented coping strategies was associated with decreased psychological distress and improved QOL. Interventions to address prognostic uncertainty and to promote approach oriented coping in patients with iNHL are sorely needed and have the potential to ameliorate psychological distress and improve QOL in this vulnerable population.
Preliminary data of a phase 1b/2 study of BCL-2 inhibitor lisaftoclax (APG-2575) alone or combined with ibrutinib or rituximab in patients (pts) with Waldenström macroglobulinemia (WM).
Authors: Ailawadhi Sikander , Lasica Masa , Fu Chengcheng , Thomas Sheeba K. , Wu Depei , Yi Shuhua , Siddiqi Tanya , Yin Qingsong , Allan John N. , Chen Wenming , Matous Jeffrey V , Feng Ru , Chen Zi , Yu Min , Li Mingyu , He Zicong , Ahmad Mohammad , Wang Hengbang , Chanan-Khan Asher Alban Akmal , Zhai Yifan
Published: June 2023

7569

Background: B-cell lymphoma 2 inhibitors (BCL-2i) are well tolerated and effective in treating B-cell lymphoproliferative disorders such as CLL. Investigational agent lisaftoclax is a novel, oral, highly selective and potent BCL-2i. Preclinical data show a strong synergistic effect of lisaftoclax plus ibrutinib in an ibrutinib-insensitive PDXWM1 model. Methods: This global, open-label, multicenter study evaluates the safety and efficacy of lisaftoclax alone and combined with ibrutinib or rituximab in pts with WM. Pts were enrolled in 3 arms: Arm A (lisaftoclax), BTKi-resistant/intolerant pts; Arm B (lisaftoclax plus ibrutinib), treatment-naïve pts; and Arm C (lisaftoclax plus rituximab), BTKi-naïve relapsed/refractory pts. Lisaftoclax was escalated from 400 to 1,200 mg using a modified toxicity probability interval design. A 3-day ramp-up was used for pts at high TLS risk. Primary objectives were pharmacokinetics (PK), safety, and efficacy assessments; responses were assessed per IWWM criteria. Results: As of January 25, 2023, 46 pts were enrolled (Arm A [n = 14]; up to 1,000 mg; Arm B [n = 24]; up to 1,200 mg; Arm C [n = 8]; up to 800 mg). Baseline characteristics are shown in the table. Median (range) treatment duration was 6 (1-18; Arm A), 14 (1-27; B), and 8 (2-26; C) months. Overall response rates (ORRs) were: Arm A, 25% (median time to response [MTTR], 4.3 months); Arm B, 90.9% (MTTR, 1.9); Arm C, 37.5% (MTTR, 4.4). No significant difference was observed between pts with and without CXCR4-mut. At 1,200 mg, 1 DLT (grade 3 clinical TLS), due to pre-existing renal impairment, was reported. At 1,000 mg, 1 grade 3 laboratory TLS occurred in Arm B because of dehydration and active symptomatic therapies; abnormal electrolytes resolved after 1 day of drug interruption, without recurrence. Grade ≥ 3 lisaftoclax-related AEs included neutropenia (13%), leukocytopenia (4.3%), anemia (2.2%), weight loss (2.2%), and septic shock (2.2%). Ventricular arrhythmias were not observed. Only 1 pt required dose reduction (due to neutropenia). MTD has not been reached. A total of 14 pts discontinued study treatment because of disease progression (n = 5) and AE (n = 1). Lisaftoclax plus ibrutinib showed a PK exposure comparable to ibrutinib alone, indicating no potential DDI. Conclusions: Lisaftoclax alone or combined with ibrutinib/rituximab demonstrated measurable effects in pts with naïve or BTKi-treatment-failed WM. Internal study identifier: APG2575WU101. *SA and ML are co-first authors. Clinical trial information: NCT04260217 . [Table: see text]
Epidemiologic characteristics, treatment patterns, and survival analysis of plasmablastic lymphoma in the US.
Authors: Hansen Alec , Vardell Victoria , Fitzgerald Lindsey
Published: June 2023

7570

Background: Plasmablastic Lymphoma (PBL) is a rare aggressive subtype of diffuse large B-cell lymphoma primarily affecting the immunocompromised, including those living with HIV. There is no established standard of care, and current survival estimates range from 8-15 months (mos). With the largest previous study of PBL limited to 590 patients (pts), we aimed to evaluate epidemiologic characteristics, treatment patterns and survival trends on a national scale. Methods: Pts diagnosed with PBL from 2010-2020 were identified in the National Cancer Database (NCDB) and the Surveillance, Epidemiology, and End Results (SEER) Program. Age-adjusted incidence rates (IR) were calculated using SEER. Demographic and treatment characteristics and overall survival were evaluated in the NCDB using Kaplan-Meier and multivariate Cox regression analysis. Results: For the 1,153 pts identified in SEER, the incidence of PBL was 0.07 per 100,000 person-years, with higher IR in males (0.12) and pts age > 75 years (0.23). IR increased on average by 4.2% per year from 2010 to 2020 (95% CI 1.51-6.96). Of the 1,822 PBL pts in NCDB, the median age at diagnosis was 57 years. PBL was more common in male (77.2%) and White pts (76.8%). Most pts presented at an advanced (III or IV) Ann Arbor stage (59.9%). Pts were HIV+ in 50.2% of cases and 51.2% had extranodal disease. The median OS (mOS) was 22.4 mos (95% CI 16.2-28.6), with a 1-, 5-, and 10-yr OS of 56%, 40%, 32%, respectively. PBL pts treated with multiagent chemotherapy (N = 862, 66%) had mOS of 58.6 mos (95% CI 43.0-74.3). Pts who received no systemic treatment (N = 456, 25%) had mOS of 1.9 mos (95% CI 1.2-2.5). Pts with Stage I disease had a mOS of 86.2 mos, Stage II of 51.1 mos, Stage III of 35.9 mos, and Stage IV of 8.8 mos. Pts with HIV had a greater mOS (44.0 mos [95% CI 28.7-59.3]) than HIV- pts (21.7 mos [95% CI 12.4-30.9]). On multivariate Cox regression adjusted for age, race, and socioeconomic status, factors associated with worse OS included age (HR 1.03 [95% CI 1.02-1.04], p < 0.001), B symptoms (HR 1.35 [95% CI 1.11-1.65], p = 0.003) and advancing stage. Factors associated with improved OS included Hispanic ethnicity (HR 0.70 [95% CI 0.52-0.93], p = 0.014) and extranodal disease (HR 0.77 [95% CI 0.63-0.93], p = 0.001). HIV+ status had no significant impact on survival (HR 1.09 [95% CI 0.87-1.38], p = 0.443). Conclusions: We present the largest study to date describing the epidemiologic, survival, and treatment patterns of PBL. In contrast to prior studies, we found a longer mOS of 58.6 mos among those treated. This may represent a large real-world population providing more accurate estimates or reflect improved outcomes from a growing number of novel therapeutic options. Notably, HIV+ status did not have a significant impact on OS. While OS remains poor, advances in treatment over the last decade are promising and highlight the need for clinical advances to improve front line therapeutic options for PBL.