bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term safety with ≥12 months of pirtobrutinib in relapsed/refractory (R/R) B-cell malignancies.
Authors: Coombs Catherine Callaghan , Shah Nirav Niranjan , Jurczak Wojciech , Woyach Jennifer Ann , Cheah Chan , Patel Krish , Maddocks Kami J. , Wang Yucai , Muehlenbein Catherine E. , Wang Chunxiao , Abhyankar Sarang , Tsai Donald Edward , Eyre Toby A. 
Published: June 2023

7513 Background: While Bruton tyrosine kinase inhibitors (BTKi) can induce sustained remissions, ongoing response requires continuous treatment and thus long-term safety/tolerability is critical for adherence, maintaining dose intensity, and delivering maximum efficacy. Pirtobrutinib is a highly selective, non-covalent (reversible) BTKi approved by the FDA in January 2023 for R/R mantle cell lymphoma after 2 prior lines of therapy including a BTKi. Pirtobrutinib has demonstrated promising efficacy with low discontinuation and dose reduction rates in patients (pts) with multiple subtypes of R/R B-cell malignancies. However, the long-term safety and tolerability of pirtobrutinib has not yet been reported. Here we report the clinical safety in pts with long-term (≥12 months) pirtobrutinib treatment from the phase 1/2 BRUIN trial. Methods: Pts with R/R B-cell malignancies who received ≥12 months of pirtobrutinib were included. Median time to onset, dose reduction, discontinuation, and cumulative incidence rates were determined for treatment emergent adverse event (TEAE) that occurred in ≥20% of pts and select AE of interest associated with BTKi. Results: As of 29 July 2022, 773 pts were enrolled, and 326 (42%) pts received treatment for ≥12 months. Among these 326 pts, median time on treatment was 19 months (IQR: 16,25), with 231 (71%) remaining on pirtobrutinib. The most common TEAE (all grade, regardless of attribution) in this long-term 326 pt cohort were fatigue (32%), diarrhea (31%), Covid-19 (29%), contusion (26%), cough (25%), and back pain (21%). TEAE leading to dose reduction or discontinuation occurred in 23 (7%) and 11 (3%) pts, respectively. Four (1%) pts discontinued due to a treatment-related AE, and 1 pt had a fatal treatment-related AE (Covid-19 pneumonia). Select AE of interest for the long-term pts are shown in the Table. Comprehensive safety analyses describing the frequency of TEAE over time will be presented. Conclusions: Prolonged pirtobrutinib therapy continues to demonstrate a safety profile amenable to long-term administration at the recommended dose without evidence of new or worsening toxicity signals. The safety and tolerability observed in pts on therapy for ≥12 months was similar to previously published safety analyses on all pts enrolled regardless of follow-up. Clinical trial information: NCT03740529 . [Table: see text]
Efficacy and safety of pembrolizumab every six weeks in relapsed/refractory classical Hodgkin lymphoma or primary mediastinal B-cell lymphoma: The phase 2 KEYNOTE-B68 trial.
Authors: McDonald Andrew Bruce , Verburgh Estelle , Gotti Manuel , Pinto Antonio , Zaucha Jan , Ivanov Vladimir , Melnichenko Vladimir , Mocikova Heidi , Ozcan Muhit , Patti Caterina , Farias Joao , Goncalves Iara , Mayer Jiří , Saydam Guray , Tomassetti Sarah , Pathiraja Kumudu , Ryland Katherine , Chakraborty Samhita , Jurczak Wojciech 
Published: June 2023

7517 Background: Pembrolizumab (pembro) 200 mg Q3W demonstrated robust antitumor activity and manageable safety in relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) and R/R primary mediastinal B-cell lymphoma (PMBCL), resulting in FDA approval. Recently, the FDA granted accelerated approval of pembro 400 mg Q6W in all approved indications based on data from solid tumor trials in solid tumors. The global Phase 2 trial (NCT04875195) evaluates the efficacy and safety of pembro 400 mg Q6W in R/R cHL and R/R PMBCL. We present, for the first time, data from 66 patients (pts) with approximately 9 months (mo) of follow up. Methods: In this nonrandomized, open-label trial, pts aged ≥18 years with PD-1 inhibitor naïve R/R cHL or PMBCL received 400 mg pembro Q6W for ≤ 18 cycles, until progression, unacceptable toxicity, or withdrawal. Eligible pts with cHL must have relapsed or failed to respond after ≥1 prior lines of therapy (LOT) or relapsed or failed to respond after ≥1 prior multiagent LOT or autologous stem cell transplant (ASCT). Eligible pts with PMBCL must have relapsed or failed to respond after ≥2 prior LOT including rituximab and relapsed or failed to respond to or were ineligible for ASCT. The primary endpoint was ORR per Lugano criteria by investigator (Lugano, INV). Secondary endpoints were DOR (Lugano, INV) and safety. Exploratory endpoints were PFS (Lugano, INV) and OS. Data cut-off date was October 18, 2022. Results: At data cut-off, 66 pts (60 R/R cHL, 6 R/R PMBCL) were enrolled. Median follow-up (range) was 8.9 mo (1 – 15.9) for pts with R/R cHL and 10.6 mo (5.1 – 15.4) with R/R PMBCL. The ORR was 65% (95% CI, 51.6 – 76.9 [33.3% CR; 31.7% PR]) for pts with R/R cHL, and 50% (95% CI, 11.8 – 88.2 [33.3% CR; 16.7% PR]) for R/R PMBCL. Drug-related adverse events (AE) occurred in 24 pts (40%) with R/R cHL and 2 pts (33.3%) with R/R PMBCL. Grade ≥3 drug-related AEs occurred in 3 pts (5%) with R/R cHL and 1 pt (16.7%) with R/R PMBCL. Immune-mediated AEs occurred in 13 pts (21.7%) with R/R cHL and 1 pt (16.7%) with R/R PMBCL. Grade ≥3 immune-mediated AEs occurred in 2 pts (3.3%) with R/R cHL. Antitumor activity is summarized in the Table. Conclusions: With approximately 9 mo of follow up, pembro 400 mg Q6W demonstrates robust antitumor activity in pts with R/R cHL and R/R PMBCL. The ORR observed is similar to pembro 200 mg Q3W in R/R cHL and R/R PMBCL. Pembro 400 mg Q6W had no new safety concerns, confirming Q6W dosing in hematologic indications. Clinical trial information: NCT04875195 . [Table: see text]
Subgroup analysis of elderly patients (pts) with diffuse large B-cell lymphoma (DLBCL) in the phase 3 POLARIX study.
Authors: Hu Bei , Reagan Patrick Michael , Sehn Laurie Helen , Sharman Jeff Porter , Hertzberg Mark , Zhang Huilai , Kim Austin Injae , Herbaux Charles , Molina Lysiane , Maruyama Dai , Smolewski Piotr , Stenner Frank , Craine Veronica , Kothari Rucha , Hirata Jamie H. , Sahin Deniz , Sugidono Matthew Dean Sei , Lee Calvin , Tilly Herve 
Published: June 2023

7518 Background: In the Phase 3 POLARIX study (NCT03274492), polatuzumab vedotin with rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) significantly improved progression-free survival (PFS) compared with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), with a similar safety profile in pts aged 18–80 years with previously untreated DLBCL (Tilly et al. 2022). Combination regimens may be associated with higher rates of toxicity in elderly pts. We report the efficacy and safety of Pola-R-CHP vs R-CHOP in pts aged ≥70 years enrolled in POLARIX. Methods: POLARIX methods were described by Tilly et al. (2022). Pts with previously untreated DLBCL were randomized 1:1 to receive 6 cycles of Pola-R-CHP or R-CHOP, plus 2 cycles of rituximab. This analysis focused on pts aged ≥70 years at enrollment. Results: Overall, 284 pts were analyzed for efficacy (Pola-R-CHP, n=141; R-CHOP, n=143) and 280 pts were analyzed for safety (Pola-R-CHP, n=137; R-CHOP, n=143). Median age was 74 years (range 70–80), and 69.7% had an International Prognostic Index score of 3–5. Most pts in either arm received all 6 doses of polatuzumab vedotin or vincristine (88.3% and 91.6% in the Pola-R-CHP and R-CHOP arms, respectively). At data cutoff (June 28, 2021; median follow-up: 24.2 months), the risk of progression, relapse or death was lower with Pola-R-CHP vs R-CHOP (hazard ratio [HR] 0.64; 95% confidence interval [CI]: 0.41–0.99) (Table). Death by any cause occurred in 14.2% and 19.6% of pts treated with Pola-R-CHP and R-CHOP, respectively. Overall survival (OS) and disease-free survival (DFS) results are presented in the Table. Safety profiles were generally comparable for Pola-R-CHP vs R-CHOP, including rates of Grade 3–5 adverse events (AEs), Grade 5 AEs, serious AEs, peripheral neuropathy (any grade), neutropenia (Grade 3–4), and infection (Grade 3–4) (Table). Conclusions: Pola-R-CHP and R-CHOP demonstrated similar safety profiles in pts aged ≥70 years with previously untreated DLBCL. The risk-benefit profile favored Pola-R-CHP vs R-CHOP. Clinical trial information: NCT03274492 . [Table: see text]
Metabolic response rates of epcoritamab + R-CHOP in patients with previously untreated (1L) high-risk diffuse large B-cell lymphoma, including double-hit/triple-hit lymphoma: Updated EPCORE NHL-2 data.
Authors: Falchi Lorenzo , Clausen Michael , Offner Fritz , de Vos Sven , Brody Joshua , Linton Kim M. , Snauwaert Sylvia , Cordoba Raul , Wu Jun , Bykhovski Irina , Wang Liwei , Rana Ali , Belada David 
Published: June 2023

7519 Background: Patients (pts) with 1L diffuse large B-cell lymphoma (DLBCL) typically receive rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP); however, around 40% relapse. Complete response rates and long-term outcomes are worse for high-risk pts with International Prognostic Index (IPI) 3–5 or double-hit/triple-hit lymphoma, representing an underserved pt population requiring better curative options. Data from the pivotal study of single-agent epcoritamab, a T-cell–engaging bispecific antibody, demonstrated impressive efficacy and a manageable safety profile (Thieblemont et al, JCO 2022). Preliminary data for epcoritamab + R-CHOP in 1L DLBCL (NCT04663347) showed encouraging efficacy. Here we present results for a larger cohort with longer follow-up. Methods: Pts with 1L CD20+ DLBCL and IPI ≥3 received subcutaneous epcoritamab (cycle [C] 1–4, QW; C5–6, Q3W) + R-CHOP for 6 Cs (21 d each) followed by epcoritamab monotherapy Q4W (28-d Cs) up to a total of 1 y. Results: As of Oct 31, 2022, 47 pts (median age, 64 y) had received epcoritamab 48 mg + R-CHOP with a median follow-up of 11.5 mo (range, 0.8–15.5). All pts had IPI 3–5, 37 (79%) had stage IV disease, and of 25 pts with FISH data available, 11 (44%) had double-hit/triple-hit DLBCL. Median time from diagnosis to first dose was 28 d (range, 3–423). Median dose intensity for R-CHOP was ≥95%. The most common treatment-emergent AEs (TEAEs) of any grade (G) were neutropenia (64%), anemia (62%), CRS (60%), fatigue (40%), pyrexia (40%), injection-site reactions (38%), and nausea (38%). TEAEs led to epcoritamab discontinuation in 3 pts; 1 pt had a G5 TEAE (COVID-19, unrelated to treatment). CRS was predominantly low grade (57% G1–2, 2% G3) and occurred mostly after the first full dose (C1D15); all cases resolved. One pt experienced G2 ICANS, which resolved. All response-evaluable pts (100%) had a response, and 76% had a complete metabolic response (CMR; Table). Notably, response rates were similar for double-hit/triple-hit pts (CMR rate, 82% [9/11]). The median durations of response, progression-free survival, and overall survival were not reached. Responses were durable; at 9 mo, an estimated 96% of pts with CMR remained in CMR. Updated data will be presented. Conclusions: Subcutaneous epcoritamab + R-CHOP induces high CMR rates with a manageable safety profile in pts with 1L high-risk DLBCL, including double-hit/triple-hit pts. These results support the ongoing phase 3 study of epcoritamab + R-CHOP in 1L pts (NCT05578976). Clinical trial information: NCT04663347 . [Table: see text]
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]