bluuebunny/crossref_metadata_2025_split huggingface dataset:
Superior outcomes after allogeneic stem cell transplantation (SCT) among patients (Pts) ≥ 60 years (yrs) treated with cladribine (CLAD), low dose cytarabine (LDAC) plus venetoclax (Ven) for newly diagnosed acute myeloid leukemia (AML).
Authors: Senapati Jayastu , Kantarjian Hagop M. , Bazinet Alexandre , Reville Patrick Kevin , Borthakur Gautam , Daver Naval Guastad , Dinardo Courtney Denton , Bataller Alex , Jabbour Elias , Short Nicholas James , Popat Uday R. , Alousi Amin Majid , Shpall Elizabeth J. , Garcia-Manero Guillermo , Ravandi Farhad , Kadia Tapan M. 
Published: June 2023

7047 Background: CLAD/LDAC/VEN alternating with AZA-VEN has shown promising outcomes in older pts with AML ( Kadia, JCO Nov 2022). Improved disease control and preserved performance status achieved with CLAD/LDAC/VEN treatment, may translate into superior post-SCT outcomes. Methods: We compared outcomes of pts ≥ 60 yrs of age treated on the phase II study of CLAD-LDAC-VEN who underwent SCT in 1st remission (CR1) to a retrospective cohort of pts ≥ 60 yrs treated with hypomethylating agent (HMA)-VEN based or intensive (INT) therapy who underwent SCT in CR1 between 2013-2022. Relapse free survival (RFS) was from response to relapse/death & overall survival (OS) from start of therapy to death. Results: 35 pts treated with CLAD-LDAC-VEN were compared to 42 pts treated with INT & 40 pts with HMA-VEN therapy for remission induction prior to SCT at our center (Table). The median age of pts in the low-intensity arms were similar (68 yrs), but lower on the INT arm (62 yrs). More pts post INT therapy received a myeloablative conditioning (MAC). At a median follow up of 17+ months (m) for CLAD-LDAC-VEN arm, 59 m for INT arm, and 30 m for HMA arm, the median RFS (NR vs. 50 m vs. 20 m respectively, p <0.01) and OS (NR vs. 58 m vs. 32 m respectively, p < 0.01) was superior for the CLAD-LDAC-VEN arm. 3-yr cumulative incidence of relapse & NRM (as competing events) were both significantly lower with CLAD-LDAC-VEN (4% and 7%) compared to INT (17% and 23%) or HMA-VEN (41% and 27%) therapy. Conclusions: Older pts with AML proceeding to SCT after CLAD-LDAC-VEN therapy had significantly improved survival, characterized by significantly lower rates of NRM and relapse compared to HMA-VEN or INT therapies. Larger studies and longer follow up is needed to confirm its benefit. [Table: see text]
Effects of ruxolitinib and magrolimab on calreticulin in myelofibrosis CD34+ cells in vitro: Proof of concept for combination therapy.
Authors: Rinaldi Ciro Roberto , Boasman Kristian , Simmonds Matthew 
Published: June 2023

7064 Background: In solid tumours, calreticulin (CALR) overexpression produces a pro-phagocytic signal and is counteracted by concomitant expression of anti- phagocytic CD47, reflecting an apoptosis vs survival mechanism. We have previously found that CD47, not CALR, is overexpressed on the membrane of patients with MPN. Anti-CD47 Magrolimab, is currently being evaluated in clinical trials in AML, MDS but have yet to be tested, either in monotherapy or in combination in MF. Methods: Mononuclear cells were collected by Ficoll separation from bone marrow of 6 MF patients and from 2 controls. CD34+ cells and monocytes were purified using Dynabeads kits from Thermofisher. Cells expression of CALR and CD47 was measured by flow cytometry, before and after incubation with ruxolitinib (Jak inhibitor) alone and in combination with magrolimab. Cells survival was calculated after combining CD34 with monocytes. Informed Consent was obtained for all samples collected. Results: CD47 membrane expression was 57% in untreated MF cells compared to 12% in the control samples and CALR membrane expression was 51.8% in untreated MF cell compared to 12.5% in the control samples. After incubation with ruxolitinib, MF CD34+ cell survival decreased to 98.2%. Following Incubation with magrolimab alone, MF CD34+ cells show no changes in survival (100% alive). The combination of ruxolitinib and magrolimab reduced slightly the MF CD34+ cell survival to 92%. A substantial membrane overexpression of CALR was observed in MF CD34+ cells when incubated with Ruxo and Magrolimab, 74.1%, vs Ruxo alone 52.6%, Magrolimab alone 53.4% and in untreated (51.8%). Interestingly, in the healthy controls, the exposure to combination therapy did not cause the same degree of CALR overexpression (20.7% vs 12.5%), indicating a much stronger pro-phagocytic effect following magrolimab/ruxolitinib combo in MF cancer cells. Conclusions: In vitro, treatment with ruxolitinib or ruxolitinib plus magrolimab, slightly reduce the overall cell survival rate in CD34+ MF samples, comparing with no significant changes in single agent magrolimab. However, the combination of Ruxolitinib and Magrolimab significantly increases CALR membrane expression comparing with Ruxo or Magrolimab alone, signalling a much stronger pro-phagocytic message in MF cells comparing with controls. The induced CALR over-expression, could stimulate a stronger immune response in vivo, where the presence of macrophages would allow removal of CALR rich cells and potentiate the cytoreductive activity towards MF clone. These data support the rational of combining Ruxolitinib with Magrolimab in the next clinical trial stage in myelofibrosis.
Pirtobrutinib in covalent BTK-inhibitor (cBTKi) pre-treated mantle cell lymphoma (MCL): Updated results and subgroup analysis from the phase 1/2 BRUIN study with >3 years follow-up from start of enrollment.
Authors: Shah Nirav Niranjan , Jurczak Wojciech , Zinzani Pier Luigi , Eyre Toby A. , Cheah Chan , Ujjani Chaitra Shankar , Izutsu Koji , Ma Shuo , Flinn Ian W. , Alencar Alvaro Jose , Lewis David John , Patel Krish , Maddocks Kami J. , Wang Yucai , Munir Talha , Zelenetz Andrew David , Balbas Minna , Tsai Donald E , Wang Chunxiao , Wang Michael 
Published: June 2023

7514 Background: Pirtobrutinib is a highly selective, non-covalent (reversible) BTKi. Here, we report updated results of pirtobrutinib in patients (pts) with cBTKi pre-treated relapsed/refractory (R/R) MCL and more than 3 years follow-up from start of enrollment. Methods: Pts with cBTKi pre-treated R/R MCL received pirtobrutinib monotherapy in a multicenter phase 1/2 BRUIN trial (NCT03740529). Efficacy was assessed in the prespecified primary efficacy cohort that comprised the first 90 enrolled pts who had measurable disease, had received a prior cBTKi, and had no known central nervous system involvement. The primary endpoint was overall response rate (ORR) as assessed by independent review committee. Secondary endpoints included duration of response (DOR) and safety. A data cut of 29 July 2022 was utilized. Results: Among MCL pts who received a prior cBTKi (n=90), median age was 70 years (range, 46-87), median prior lines of therapy were 3 (range, 1-8), 82% discontinued a prior cBTKi due to disease progression, and 78% had intermediate/high risk sMIPI score. Of samples available, 17/36 (47%) had TP53 mutations and 25/34 (74%) had Ki67 ≥30%. The ORR was 57% (95% CI, 46-67), including 19% complete responses (n=17) and 38% partial responses (n=34). At a median follow-up time of 13 months, the median DOR among the 51 responding pts was 17.6 months (95% CI, 7.3-27.2). The 12- and 18-month estimated DOR rates were 58% (95% CI, 41-72) and 45% (95% CI, 27-61), respectively. ORR and DOR by subgroups are shown in the Table. The median progression-free survival was 7.4 months (95% CI, 5.3–13.3). The median overall survival was 23.5 months (95% CI, 15.9-NE). In the MCL safety cohort (n=166), the most frequent treatment-emergent adverse events (TEAE) were fatigue (31%), diarrhea (22%), and anemia (17%). The most common Grade ≥3 TEAE was neutropenia (15%). Grade ≥3 TEAE of hemorrhage (3%) and atrial fibrillation/flutter (2%) were infrequent. Only 5 (3%) pts discontinued due to a treatment-related AE. Conclusions: Pirtobrutinib continues to show durable efficacy and a favorable safety profile in heavily pre-treated R/R MCL pts with prior cBTKi therapy. Responses were observed in pts with high-risk disease features including pts with blastoid/pleomorphic variants, elevated Ki67 index, and TP53 mutations. Clinical trial information: NCT03740529 . [Table: see text]
Impact of imaging frequency on progression free survival in Alliance clinical trials enrolling patients with untreated follicular lymphoma.
Authors: Rutherford Sarah C. , Yin Jun , Pederson Levi D , Blum Kristie A. , Martin Peter , Jung Sin-Ho , Grant Barbara , Rosenbaum Cara , Cheson Bruce D. , Bartlett Nancy L. , Mandrekar Sumithra J. , Leonard John Paul 
Published: June 2023

7520 Background: With goal of simplifying clinical trials in lymphomas, we reported that bone marrow biopsies are irrelevant for response assessment in most patients (pts) with follicular lymphoma (FL) on trials (Rutherford JCO 2023). We then investigated impact of imaging frequency in FL clinical trials. We hypothesized that progression free survival (PFS) would not be different when imaging is performed less frequently than required by trials. Methods: We identified all trials through Alliance for Clinical Trials in Oncology that enrolled untreated pts with FL from 2008-2016. We considered 2 imaging schedules: protocol specified (control) vs relaxed (X) in which response assessments at every other required time point were omitted. For each trial, we estimated PFS using Kaplan Meier methods for the 2 schedules then determined difference in PFS between schedules as % change from control schedule in 2 year (yr) PFS rate. We performed simulation studies to approximate impact of less frequent imaging on PFS estimation using 50901 (low-intermediate risk FL) and 50904 (intermediate-high risk FL, control arm). We assumed exponential distribution for PFS, where rate parameter was calculated based on observed median PFS with uniform censoring distribution. Protocols for 50901 and 50904 mandated imaging every 4 months (mos) for 2 yrs then every 6 mos (S0). We ran 1000 iterations of 100 observations using 3 tumor assessment follow up schedules: every 6 mos for 2 yrs then yearly (S1), every 8 mos for 2 yrs then yearly (S2), or yearly (S3) for simulated progression times. We calculated deviation of PFS using simulated schedules from truth (S0). Results: Across 5 FL trials, median percent change of schedule X from control schedule in estimated 2yr PFS was 2.1% (0.0-30.8%) and in estimated 4yr PFS was 0.9% (-8.6-25.7%). Disparate result in 50901 is due to small shift in events with low number of pts at risk for progression. Simulation study results by trial were: for 50901, true median PFS 1.9 yrs and average median PFS for S1, S2, and S3 of 2.05, 2.11, and 2.21 yrs; for 50904 (control arm), true median PFS 4.1 yrs and average median PFS for S1, S2, and S3 of 4.16, 4.12, and 4.05 yrs. Conclusions: Our findings support decreased frequency of imaging studies in FL clinical trials, which would improve resource use and decrease pt burden. We plan a larger analysis to confirm results. https://acknowledgments.alliancefound.org . Clinical trial information: NCT00553501 , NCT01145495 , NCT01190449 , NCT01286272 , NCT01829568 .[Table: see text]
Effectiveness and safety outcomes in patients with EBV+ PTLD treated with allogeneic EBV-specific T-cell immunotherapy (tabelecleucel) under an expanded access program (EAP) in Europe.
Authors: Choquet Sylvain , Clark Andrew , Renard Cécile , Uttenthal Ben , Chaganti Sridhar , Trappe Ralf Ulrich , Comoli Patrizia , Duan Xinyuan , Xing Baodong , Wu Charley , Gamelin Laurence , Terwey Jan-Henrik , Friedetzky Anke , Dierickx Daan 
Published: June 2023

7521 Background: Pts with relapsed or refractory (r/r) EBV+ post-transplant lymphoproliferative disease (PTLD) in Europe have had historically poor overall response rates and median overall survival (OS) with no approved treatment options. Tabelecleucel, an off-the-shelf, allogeneic EBV-specific T-cell immunotherapy has shown clinical benefit and favorable safety profile in the treatment of EBV+ PTLD failing rituximab ± chemotherapy (Prockop EBMT 2021, ATC 2021, ASH 2022). Its recent European marketing authorization (EMA) represents the first approval of an allogenic T-cell immunotherapy globally. Methods: Atara Bio supported expanded access requests for tabelecleucel in Europe. Here we report updated effectiveness and safety data for r/r EBV+ PTLD pts who provided consent for research between Sep 2020 and Dec 2022. Results: 74 EAP requests were received from 10 countries for pts with r/r EBV+ diseases. 27 EBV+ PTLD pts consented to secondary use of data and 24 pts had received ≥1 dose of tabelecleucel, including 4 pts with primary central nervous system (PCNS) PTLD. 16 of 24 (66.7%) PTLD pts achieved a partial (PR) (33.3%) or complete (CR) (33.3%) response, with median time to response (TTR) of 1.0 mo (0.8–2.2). Response rate for PCNS PTLD pts was 75% (1 CR, 2 PR). 1-yr OS Kaplan–Meier (KM) estimate rates were 73.7% (95% CI: 47.3, 88.3) overall, 87.5% in allogeneic hematopoietic stem cell transplant (HCT) and 66.5% in solid organ transplant (SOT), with a median follow-up time of 9.9 (2.4–13.9) and 6.0 (0.7–18.0) mo, respectively. Serious treatment-emergent adverse events (TESAEs) were reported in 7 (29.2%) pts, including 1 fatal event of disease progression. Predefined risks for tabelecleucel were reported in 3 pts; 1 (4.2%) SOT pt had a TESAE of liver transplant rejection (grade 2) and 2 (8.3%) HCT pts had non-serious TEAEs of chronic graft-versus-host disease (grade 1 and 2). No cases of cytokine release syndrome or tumor flare reaction were reported. No AEs were reported as related to tabelecleucel by the treating physician. Conclusions: These updated real-world results for pts with r/r EBV+ PTLD post-HCT or post-SOT treated in the European EAP continue to reinforce the favorable risk:benefit profile of tabelecleucel and are in line with clinical study data supporting its recent EMA approval. [Table: see text]
Analysis of racial disparities accounting for treatment received in chronic lymphocytic leukemia: A real-world cohort analysis.
Authors: Kittai Adam , Huang Ying , Bhat Seema Ali , Clark Abi , Grever Michael R. , Roberts Melyssa , Rogers Kerry Anne , Teschemaker Anna , Munoz-Sagastibelza Maria , Woyach Jennifer Ann , Barrientos Jacqueline Claudia 
Published: June 2023

7533 Background: Recent population-based studies have shown that Black patients (pts) with CLL have worse overall survival (OS) than White pts with CLL. These studies could not account for the use of modern therapies, CLL prognostic variables, or comorbidity and thus the root cause of this disparity remains unclear. Here, we use the Flatiron Health Database (FHD) to study this disparity, while accounting for disease-specific variables and treatment (tx) received. Methods: Retrospective analysis of pts with CLL in the FHD treated between 2002 to 2022 was performed. Pt characteristics such as age at diagnosis (dx), year (yr) of dx, months (mos) from dx to first tx, race, sex, IGHV status, ECOG performance status (PS), and use of small molecule inhibitors at any time (including BTK inhibitors, venetoclax, PI3K inhibitors, and lenalidomide) were collected and analyzed. OS was measured from tx start. Multivariable cox regression (MVA) was used to determine adjusted odds of survival. Results: 13646 pts with CLL were identified. Mean age at dx was 65.3 yrs, and mean time from dx to tx was 32.3 mos. 81.2%, 8.4%, and 10.4% of pts were White, Black, or other race, respectively, and 63.2% of pts were male. 61.4% of pts were IGHV unmutated, and 89.1% of pts had a ECOG PS 0/1. 58.7% of pts were treated with a small molecule inhibitor at any point during their tx. After a median follow-up of 5.3 yrs, the median OS was 10.5 yrs (95% CI: 10.2-10.8). Black pts were younger at dx (63.1 vs 65.4), had shorter time to first tx (23.6 mo vs 34 mo), were more likely to be IGHV unmutated than White pts (83% vs 60.1%), and had more small molecule inhibitor use (69% vs 58.5%). These differences were all statistically significant (p <0.01). 90.8% and 89.1% of Black and White pts had an ECOG PS of 0/1, respectively. Median OS for Black pts was 10 yrs (95% CI: 9.1-11.1) vs 10.5 yrs (95% CI: 10.2-10.8) for White pts. On MVA, Black pts had higher risk of death than White pts of the same age despite increased use of small molecule inhibitor (Table). However, the interaction between age and race was also significant, indicating a decreasing disparity between Black and White race as pts aged. Time to first tx, IGHV unmutated status, and ECOG PS were also independently associated with worse OS. Conclusions: Black race especially at younger age was independently associated with worse OS despite the use of small molecule inhibitors, IGHV status, and ECOG PS. [Table: see text]
Outcomes among adult recipients of CD19 CAR T-cell therapy for Burkitt lymphoma.
Authors: Samples Laura S. , Sadrzadeh Hossein , Frigault Matthew J. , Jacobson Caron Alyce , Hamadani Mehdi , Gurumurthi Ashwath , Strati Paolo , Shouval Roni , Riedell Peter A. , Dahiya Saurabh , Yared Jean , Jain Michael D. , Locke Frederick L. , Leslie Lori Ann , Epperla Narendranath , Ghosh Monalisa , Skarbnik Alan , Hill Brian T , Kamdar Manali K. , Shadman Mazyar 
Published: June 2023

7571 Background: Burkitt lymphoma (BL) is a rare, but highly aggressive B-cell lymphoma associated with especially poor outcomes in patients with relapsed/refractory disease. Multiple CD19 chimeric antigen receptor (CAR) T-cell products have been FDA approved to treat relapsed/refractory B-cell non-Hodgkin lymphoma in the second-line setting, however little is known about CAR T-cell responses in patients with BL. This multicenter study aims to assess real-world outcomes among patients with BL treated with CAR T-cell therapy across the United States. Methods: This multicenter, retrospective chart review was conducted by abstracting data from the medical charts of patients with BL who received CAR T-cell therapy. Demographic characteristics were assessed along with pre-CAR treatments, bridging therapies, infusion-related complications, CAR-T responses, and the use of post-CAR systemic therapy and/or hematopoietic stem cell transplant. Results: A total of 13 patients with relapsed/refractory BL received CAR T-cell therapy after a median of 3 prior therapies (range 1-6). Most patients received axi-cel (n = 8), although tisa-cel (n = 3) and liso-cel (n = 2) were also represented. The median age of these patients was 38 (range 24-68). A total of 6 (46.2%) had evidence of central nervous system involvement at diagnosis and 5 (38.5%) had a prior history of autologous stem cell transplant. The overall response rate 1 month after infusion was 69.2% with a complete response rate of 53.8%. All patients experienced grade 1-2 cytokine release syndrome (CRS). No one experienced grade ≥3 CRS, but 2 patients developed grade ≥3 immune effector cell-associated neurotoxicity syndrome (ICANS). Twenty-eight-day mortality was 23%, including one patient who died from grade 4 ICANS. Regarding long term data, only 4 (30.8%) patients sustained a complete response for more than 6 months. Median progression-free survival was 4.2 months (95% CI 28.2-257.6), and the 1-year overall survival rate was 61.5% (95% CI 0.56-0.67). Two (15.4%) patients received consolidative allogeneic stem cell transplants after CAR T-cell therapy, but both ultimately developed progressive disease. Conclusions: Relapsed/refractory BL is a rare and aggressive disease that remains challenging to treat despite the advent of CAR T-cell therapy. Further investigation is needed to determine the most effective management of these patients. We expect to include additional patients in this analysis over the coming months.
A phase 3, open-label, randomized study to evaluate the efficacy and safety of single-agent belantamab mafodotin (belamaf) compared to pomalidomide plus low-dose dexamethasone (Pd) in patients (pts) with relapsed/refractory multiple myeloma (RRMM): DREAMM-3.
Authors: Weisel Katja , Hungria Vania TM , Radinoff Atanas , Delimpasi Sosana , Mikala Gabor , Masszi Tamas , Li Jian , Capra Marcelo , Matsumoto Morio , Sule Neal , Li Mary , McKeown Astrid , He Wei , Bright Shelley , Currie Brooke , Boyle Julia , Opalinska Joanna , Dimopoulos Meletios A. 
Published: June 2023

8007 Background: Belamaf, an antibody-drug conjugate targeting B-cell maturation antigen, induces cell death by direct cell kill and immune-mediated mechanisms. The DREAMM-2 trial (NCT03525678) showed rapid, deep and durable responses to belamaf monotherapy in pts with RRMM. The Phase 3, open-label, randomized, multicenter DREAMM-3 trial (NCT04162210) evaluated belamaf monotherapy vs Pd in adult pts with RRMM at second relapse (third line) or later. Methods: Pts were randomized (2:1) to belamaf 2.5 mg/kg Q3W or Pd (pom 4 mg PO daily on days 1–21 of 28 day cycle; dex, 40mg PO [20mg if >75 years]) Q1W. The primary endpoint was progression free survival (PFS). Results: 325 pts were enrolled (belamaf n=218, Pd n=107). Median (range) age was 68 (38–90) years; 57% were male. Median (range) duration of exposure for belamaf was 4.1 (0.4, 22.9) months (mo) and 5.3 (0.4, 24.0) for Pd. Median (range) duration of follow-up was 11.5 (0.6, 24.2) mo for belamaf and 10.8 (0.0, 26.4) mo for Pd. Median PFS was longer for belamaf (11.2 [6.4, 14.5] mo) vs. Pd (7.0 [4.6, 10.6] mo). There was no statistically significant difference in PFS between the 2 treatment groups, (HR 1.03 [95% CI: 0.72, 1.47]), based on the stratified Cox model (p=0.558). Belamaf induced deeper responses vs Pd (Table). Median duration of response (DoR) was more durable for belamaf than for Pd (Table). At 12 mo, the probability (95% CI) of maintaining response was 0.768 (0.641, 0.854) for belamaf and 0.484 (0.258, 0.679) for Pd. Median PFS2 was 18.7 mo (95% CI 14.5, NR) for belamaf and 12.7 mo (9.3, 21.1) for Pd. PFS2 rate at 6 mo was 73% for belamaf and 76% for Pd. Overall survival (OS) data were immature (37.5% overall maturity) at this analysis; median OS was 21.2 mo (95% CI 18.7, NR) for belamaf and 21.1 mo (15.1, NR) for Pd (HR 1.14 [95% CI 0.77, 1.68]; p=0.746). Adverse events (AEs) were reported in 97% and 93% of patients (Table). The safety profile was consistent with previous reports for belamaf and Pd. Conclusions: Belamaf monotherapy did not demonstrate PFS superiority when compared to a doublet (Pd). However, median PFS was longer for belamaf monotherapy and belamaf induced deeper, more durable responses than Pd. No new safety signals were observed. Subgroup analyses and PRO outcomes will be reported. Belamaf continues to be investigated in combination with established and novel agents.[Table: see text]