bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patients with radioiodine-refractory differentiated thyroid cancer (RAI-R DTC) with BRAF V600E and/or K601E mutation status: A real-world view of effectiveness of lenvatinib monotherapy.
Authors: Worden Francis P. , Wirth Lori J. , Reynolds Neil , Cooper Charley , Rajkovic-Hooley Olivera , Milligan Gary , Pham Phananh , Saal Hakim , Brose Marcia S. 
Published: June 2024

6098 Background: Lenvatinib was approved for the treatment of patients RAI-R DTC in the United States (US) in 2015, and the treatment landscape has evolved with agents targeting specific driver mutations. We assessed real-world clinical effectiveness of first line therapy with lenvatinib in patients with BRAF-mutated tumors, wild-type (WT) tumors, and patients who have not been tested for BRAF mutations (BRAF untested tumors). Methods: A retrospective chart review of RAI-R DTC patients in the US who initiated first-line lenvatinib monotherapy between February 13, 2015, and September 30, 2020. Data, including a boosted cohort of patients with BRAF-mutated tumors collected in late 2023, were abstracted from patients’ electronic health records and were de-identified. Descriptive analyses were conducted in patient cohorts with BRAF V600E and/or K601E mutated tumors, wild-type (WT) tumors, and BRAF untested tumors. Best response in first-line therapy was captured, real-world progression-free survival (rwPFS) and real-world overall survival (rwOS) were assessed using Kaplan-Meier methods. Results: Of the 361 patients reviewed, 185 had records showing BRAF mutational status testing. 89 had BRAF V600E and/or K601E mutated tumors, 96 had WT tumors. 176 patients did not have BRAF mutational assessment. Of all subjects, 73.7% were White/Caucasian, 15.2% were African American, and 16.8% were Hispanic/Latino; 27.1% had ECOG performance status ≥2. The median follow-up times for each cohort were 30.0, 18.7 and 18.0 months, showing the longer follow up period for the BRAF-mutated cohort boost. Kaplan-Meier estimation for lenvatinib treatment discontinuation for the three cohorts at 24-months were as shown in the table below. Provider-reported overall response rate (complete or partial response) was 76.4%, 75.0% and 69.3% respectively. The estimated 24-month rwPFS rates (95% CI) were 74.1% (62.2%-82.8%), 61.7% (49.6%-71.8%), and 69.8% (60.9%-77.0%) respectively. Median rwOS was not reached for patients with BRAF-mutated and WT tumors, median OS was 54.2 months for BRAF untested tumors. Estimated rwOS rates at 12- and 48-months were 93.2% (85.4%-96.9%) and 83.9% (73.3%-90.3%) in BRAF-mutated patients, 90.6% (82.8%-95.0%) and 68.5% (53.4%-79.6%) in WT patients, and 90.2% (84.7%-93.8%) and 72.5% (61.6%-80.7%) in BRAF untested patients respectively. Conclusions: In this US real-world experience, the effectiveness of lenvatinib is consistent across a diverse cohort of RAI-R DTC patients with BRAF-mutated, WT, and BRAF untested tumors. This has implications for the first-line use of lenvatinib in BRAF mutated patients. [Table: see text]
Preclinical assessment of IPH6501, a first-in-class IL2v-armed tetraspecific NK cell engager directed against CD20 for R/R B-NHL, in comparison with a CD20-targeting T cell engager.
Authors: Demaria Olivier , Vetizou Marie , Remark Romain , Chiossone Laura , Vagne Constance , Courtois Rachel , Denis Caroline , Maguer Aurélie , Le Floch François , Represa Agnès , Blanchard Alvarez Audrey , Gauthier Laurent , Quaratino Sonia , Paturel Carine , Vivier Eric 
Published: June 2024

7030 Background: The therapeutic landscape for relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL) is evolving to include targeted T-cell based immunotherapies, including CD19-targeted CAR-T and CD3xCD20 T-cell engaging (TCE) bispecific antibodies. Yet, there remains an unmet medical need for patients who are refractory to, or ineligible for these treatments. Leveraging natural killer (NK) cells emerges as a promising strategy in hematological malignancies, as shown in a Phase 1 study with IPH6101/SAR’579 in R/R AML (Stein, ASCO 2023; Bajel, ASH 2023). Methods: We developed IPH6501, a tetraspecific antibody-based NK cell engager that simultaneously targets on NK cells the CD16a and NKp46 receptors, the IL-2 receptor with an engineered IL-2 variant (IL2v) and on B-NHL cells the CD20 antigen. This approach boosts NK cell activation and proliferation, cytotoxicity against tumor cells, and cytokine production. The IL-2 variant is designed with mutations that prevent binding to CD25 (IL-2Rα), limiting Treg activation and potential IL-2-related side effects. IPH6501 has been evaluated in mouse, non-human primate, and human-derived models, including cells from R/R B-NHL patients. Results: In vivo studies in non-human primates and tumor mouse models revealed that IPH6501, at well-tolerated doses, significantly boosted peripheral NK cell proliferation, drove their accumulation at tumor locations, and effectively eradicated CD20+ cells in blood and tissues. In human derived-models, IPH6501 significantly induced NK cell proliferation and cytotoxicity. Notably, IPH6501 showed potent activity against a range of B-NHL cell lines, including those with low CD20 expression. In addition, IPH6501 upregulated the expression of activating receptors on NK cells, such as NKG2D, essential for the recognition and killing of malignant cells, thereby introducing another mode of action enabling the elimination of CD20-negative tumor cells. In a comparative analysis with a CD3xCD20 TCE, IPH6501 induced lower cytokine secretion, suggesting a potentially safer profile. Additionally, IPH6501 showed higher killing efficacy compared to the TCE in samples from healthy individuals as well as R/R B-NHL patients, underscoring its therapeutic potential. Conclusions: The preclinical demonstrations of IPH6501 activities across various in vivo models and its effectiveness in ex vivo assays using cells from R/R B-NHL patients provide compelling evidence of its therapeutic potential and tolerability. IPH6501 is emerging as a promising new candidate within the treatment landscape for R/R B-NHL and is currently being investigated in a global, first-in-human phase 1/2 study (NCT 06088654).
Epcoritamab + R-DHAX/C in transplant-eligible patients (pts) with high-risk relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL).
Authors: Karimi Yasmin , Abrisqueta Pau , de Vos Sven , Nijland Marcel , Offner Fritz , Osei-Bonsu Kojo , Rana Ali , Archer Kimberly G. , Song Yaou , Cordoba Raul , Falchi Lorenzo 
Published: June 2024

7032 Background: While high-dose therapy (HDT)–autologous stem cell transplant (ASCT) is potentially curative for pts with R/R DLBCL, many do not receive this treatment (tx) due to insufficient response to salvage chemoimmunotherapy; better options are needed. Epcoritamab is a CD3xCD20 bispecific antibody with efficacy and safety in R/R DLBCL as a single agent and in combination. We report updated data from epcoritamab in combination with rituximab, dexamethasone, cytarabine, and oxaliplatin or carboplatin (R-DHAX/C) in pts with R/R DLBCL eligible for HDT-ASCT, including high-risk pts (progressed within 12 mo of initial tx or primary refractory), from EPCORE™ NHL-2 (phase 1/2; NCT04663347). Methods: Adults with R/R CD20+ DLBCL eligible for HDT-ASCT received R-DHAX/C and epcoritamab (2 step-up doses, then 24- or 48-mg full doses) in 21-d cycles (Cs): QW, C1–3. If HDT-ASCT was deferred, pts could continue epcoritamab (21-d C: QW, C4; 28-d Cs: Q2W, C5–9; Q4W, C≥10) until disease progression. Primary endpoint was overall response rate (ORR; Lugano criteria). Results: As of Dec 15, 2023, 29 pts (median age, 58 y) received epcoritamab (24 mg, n=3; 48 mg, n=26) + R-DHAX/C. At baseline, 24 pts (83%) had progressed within 12 mo of initial tx, 19 (66%) had primary refractory disease (no response or relapse within 6 mo of initial tx), and 3 (10%) had prior CAR T. At 27.5 mo median follow-up, 16 (55%) pts had proceeded to HDT-ASCT and 2 (7%) remained on tx. ORR was 76% and complete response (CR) rate was 69% (Table). Median time to response was 1.4 mo (CR, 1.5 mo). At 24 mo, per Kaplan–Meier estimates, 60% of pts remained progression free, while 90% of pts who proceeded to ASCT (n=16) and 60% of pts who continued epcoritamab without ASCT (n=5) remained progression free; additionally, 90% of pts with CR who received ASCT (n=15) and 100% of high-risk pts with CR who received ASCT (n=12) remained in response. An estimated 86% of pts remained alive at 24 mo. The most common tx-emergent AEs (TEAEs) of any grade (G) were thrombocytopenia (76%), anemia (59%), nausea (48%), and neutropenia (48%; febrile neutropenia, 17%). CRS was low grade (38% G1, 7% G2), resolved, and did not lead to tx discontinuation. ICANS (G2) occurred in 1 pt and led to tx discontinuation. There were no fatal TEAEs. Conclusions: Longer follow-up reaffirms the efficacy and feasibility of epcoritamab + R-DHAX/C in ASCT-eligible DLBCL. Response rates were high and most pts proceeded to ASCT. Safety was manageable and consistent with prior data. These results, including new high-risk subgroup analyses, support future evaluation of epcoritamab + R-DHAX/C in ASCT-eligible DLBCL. Clinical trial information: NCT04663347 . [Table: see text]
First-line (1L) treatment of follicular lymphoma (FL) with atezolizumab and obinutuzumab (A+O) +/- radiotherapy (RT): Results from the FLUORO study.
Authors: Chong Geoffrey , Lee Denise , Lee Sze Ting , Grobler Anneke , Khor Richard , Campbell Belinda A. , Thachil Thanuja , Manos Kate , Martynchyk Arina , Douglas Genevieve , Keane Colm , Palmer Jodie , Hawkes Eliza Anne 
Published: June 2024

7070 Background: Standard 1L immunochemotherapy in FL is highly effective but not without significant toxicity. Up to 75% of FL patients (pts) have grade 3-5 adverse events (AEs), primarily infection and myelosuppression. More tolerable approaches are needed. PD1/PDL1 inhibitors are active in FL. A+O yield responses in 57% of rituximab-refractory FL pts (Palomba 2017). Our phase 2 study of 1L nivolumab + rituximab in FL yielded 92% overall response rate (ORR), (54% Complete Response (CR)). Toxicity compared favourably with chemotherapy: 41% grade 3-5 AEs (Hawkes 2021). FL is sensitive to low dose RT, with proven abscopal effects, is safe and synergistic with PDL1i (Hawkes 2023), potentially improving treatment efficacy with minimal extra toxicity. This investigator-led, multicentre PET-adapted phase 2 trial assessed A+O +/- RT efficacy for treatment-naïve FL. Methods: ‘FLUORO’ (NCT03245021) is an open-label, multi-centre, phase 2, Simon’s 2-stage study of A+O+/-RT (N = 46; 15 in initial cohort). Key eligibility were stage II-IV grade 1-3A FL requiring therapy; ECOG ≤2; adequate organ function. All pts received 6 cycles (C) of A 1200mg + O 1000mg IV 3-weekly (plus O on C1, days 8 & 15). Pts with < CR on PET post C2 had RT (4Gy) to residual PET-avid disease. Pts with CR or PR(partial response) received 12 cycles 8-weekly maintenance O. Primary endpoint (EP) was CR rate with <5/15 CR deemed futile in 1st stage. Secondary EP included ORR, Progression-free survival (PFS), overall survival (OS) and AEs. Exploratory EP included biomarker studies and PET radiomics. Results: 16 pts were enrolled from 08/2021-10/2022, 1 pt was replaced due to Grade(G) 4 infusion reaction to O requiring cessation. Baseline characteristics included median age 53y (range 33-79), stage IV disease in 81%, B symptoms in 12.5%, 44% had FLIPI >2. Primary EP was met, with CR at end of induction in 13/15 (87%) evaluable pts (ORR 100%). 12 pts (80%) required RT. 2 pts (13%) discontinued due to progressive disease (Table). AEs were mostly G1-2; fatigue 44%, constipation 31%, nausea 25%. fever 25%, abdominal pain 18.6%. SAEs were reported in 7/16 (44%) pts, including grade 3 infections: COVID19 12%, upper respiratory tract 12%, urinary tract 6.2%. Median follow-up is 24m (range 16-28) and ongoing, 16m PFS & OS is 87% & 100%. Biomarker analysis is ongoing. Conclusions: Atezolizumab +Obinutuzumab +/- PET-adapted 4Gy RT yielded high complete response rates with low toxicity in treatment-naïve FL. CR threshold to proceed to stage 2 was met, however was not deemed commercially viable. Clinical trial information: NCT04962126 .[Table: see text]
Impact of extramedullary multiple myeloma on outcomes with idecabtagene vicleucel.
Authors: Zanwar Saurabh , Sidana Surbhi , Shune Leyla , Castaneda Puglianini Omar Alexis , Pasvolsky Oren , Gonzalez Rebecca , Dima Danai , Afrough Aimaz , Kaur Gurbakhash , Davis James A. , Herr Megan , Hashmi Hamza , Forsberg Peter A. , Sborov Douglas W. , Richard Shambavi , Khouri Jack , Lin Yi , Patel Krina K. , Kumar Shaji , Hansen Doris K. ,   US Multiple Myeloma Immunotherapy Consortium
Published: June 2024

7508 Background: Idecabtagene vicleucel (Ide-cel) has demonstrated excellent efficacy in patients with relapsed/refractory multiple myeloma (RRMM). However, outcomes in patients with extramedullary disease (EMD) remain to be better characterized. Methods: We included patients from 11 US academic centers, who were evaluated for EMD and were infused with ide-cel between May 2021 and April 2023. Patients with soft tissue or visceral lesions non-contiguous from bony lesions were classified as having true EMD, with paraskeletal disease classified as non-EMD. Disease responses were evaluated using the IMWG criteria. Time-to-event analyses were performed from the date of ide-cel infusion. Results: Among 351 patients with RRMM treated with ide-cel, 84 (24%) had EMD prior to infusion. Median follow-up for the entire cohort was 18.2 months (95% CI: 17-19.3). Baseline characteristics at ide-cel infusion for EMD and non-EMD cohorts are depicted in the table. For the EMD and non-EMD cohorts, the Day 30 objective response rates (ORR) were 58% vs. 69% (p=0.1), Day 30 ≥complete response rates were 16% vs 24% (p=0.11), the Day 90 ORR were 52% vs 82% (p<0.001), and best ORR were 58% vs 82%, respectively. The median progression-free survival (PFS) was 5.3 months (95% CI: 4.1-6.9) for the EMD cohort vs. 11.1 months (95% CI: 9.2-12.6; p<0.0001) for the non-EMD cohort. The median duration of response for EMD among day 30 responders was 6.4 months (95% CI: 5.1-8.4). In a multivariable analysis, EMD was an independent predictor of inferior PFS [hazard ratio 1.8 (95% CI: 1.2-2.5), p<0.001] after adjusting for ECOG status, revised ISS stage, penta-drug refractoriness, elevated ferritin, prior BCMA-directed therapy and use of bridging therapy. Pattern of progression in the EMD cohort (n=68/84) included EMD site only (21%), hematologic only (22%), or both (57%), with comparable PFS for type of progression (p=0.19). The median overall survival (OS) was 14.8 months [95% CI: 9-Not reached (NR)] for EMD and 26.9 months [95% CI: 26.3 vs NR, p=0.006)] for the non-EMD group. Rates of Grade ≥2 cytokine release syndrome or neurotoxicity syndrome were comparable between the two cohorts. Conclusions: Patients with EMD demonstrate significantly inferior Day 90 ORR and presence of EMD is an independent risk factor for inferior PFS. [Table: see text]
Apixaban versus warfarin for primary thromboprophylaxis in patients with multiple myeloma undergoing immunomodulatory treatment.
Authors: Chang Yu-Cheng , Chiang Cho Han , Tang Zhiting , See Xin Ya , Chiang Cho Hung , Chi Kuan-Yu , Chang Yu , Gao Wenli 
Published: June 2024

7548 Background: Immunomodulatory drugs (IMiDs) have been demonstrated to improve clinical outcomes in patients with multiple myeloma (MM), but are associated with an elevated risk of thromboembolism. Existing guidelines recommend low-dose direct oral anticoagulants as an alternative to warfarin for primary thromboprophylaxis in MM. However, the data comparing these two therapies are limited. We aim to compare the efficacy and safety of apixaban versus warfarin in patients with MM undergoing IMiD treatment. Methods: We conducted a retrospective propensity score-matched cohort study using the TriNetX Analytics Network database, which contains de-identified data from over 120 participating healthcare institutions. We included adult patients with MM who underwent IMiD treatment. Patients treated with apixaban were matched in a 1:1 ratio to those treated with warfarin using clinical variables a priori. The primary safety outcomes included all-cause mortality, intracranial hemorrhage, and gastrointestinal bleeding, while the primary efficacy outcomes included thromboembolic events including pulmonary embolism, deep venous thrombosis, and ischemic stroke within a 3-year period following IMiDs initiation. Results: We identified 448 patients on apixaban who were matched to patients on warfarin. In a Cox proportional hazard analysis, apixaban was associated with a 30% lower risk of all-cause mortality compared to warfarin (Hazard ratio (HR), 0.70 [95% CI: 0.56-0.88]).There was a tendency toward a reduced risk of gastrointestinal bleeding in patients treated with apixaban compared to warfarin (HR, 0.58 [95% CI: 0.31-1.08], log-rank p = 0.083). The risk of intracranial hemorrhage was similar between the two groups.The risks of thromboembolic events including pulmonary embolism, deep venous thrombosis, and ischemic stroke were comparable between the apixaban and warfarin cohorts. Conclusions: Apixaban was associated with a lower risk of all-cause mortality and a comparable risk of bleeding and thromboembolism compared with warfarin among MM patients undergoing immunomodulatory treatment. [Table: see text]
Real world outcomes of high dose melphalan conditioning prior to autologous stem cell transplant in extramedullary multiple myeloma vs. multiple myeloma without extramedullary involvement: A single center experience.
Authors: Poei Darin , Parker Graham Blake , Ye Shirley , Tun Han , Ranganathan Raghuveer , Myint Zaw Win 
Published: June 2024

7550 Background: Extramedullary multiple myeloma (EMM) is defined as the presence of multiple myeloma plasma cells, which develop outside of the bone marrow. It is an aggressive form of multiple myeloma that is associated with a poor prognosis. The current standard of care for multiple myeloma consists of induction, high dose melphalan autologous stem cell transplant (ASCT), followed by maintenance. However, there is limited data on the outcome of patients with extramedullary multiple myeloma who undergo ASCT. Therefore, we examined the outcomes of high dose melphalan conditioning prior to ASCT in EMM patients compared to multiple myeloma patients without extramedullary involvement (non-EMM) at an academic institution in Los Angeles. Methods: We retrospectively reviewed 246 multiple myeloma patients who underwent ASCT after receiving high dose melphalan conditioning at USC Norris Comprehensive Cancer Center from Jan 2017 to Dec 2022. The cohort was subdivided into 70 EMM patients and 176 non-EMM patients. Outcomes were measured as the status of disease response, which was evaluated at 100 days (D+100) and 365 days (D+365) after the date of transplant. Results: In the EMM group, 1.43% (n=1) was found to have progression at D+100 and 12.86% (n=9) at D+365. In the non-EMM group, 0.57% (n=1) was found to have progression at D+100 and 11.93% (n=21) at D+365. There was no statistical significance between the EMM and non-EMM groups for progression free survival at D+100 (p-0.50) and D+365 (p-0.75). Regarding overall survival, there were 0 deaths observed at D+100 in both the EMM and non-EMM groups. For D+365, the overall survival was 98.57% (n=69) for the EMM group and 99.43% (n=175) for the non-EMM group. There was no statistical significance between the overall survival at D+365 (p-0.14). Conclusions: The EMM cohort exhibited similar rates of progression free survival (87.14% vs. 88.07%) and overall survival (98.57% vs. 99.43%) compared to the non-EMM cohort at one year post ASCT after receiving high dose melphalan conditioning. We observed that there was no significant statistical difference between the EMM and non-EMM cohorts regarding progression-free survival (p-0.75) and overall survival (p-0.14) on day 365. According to our data, high dose melphalan conditioning prior to autologous stem cell transplant is equally as effective for patients with multiple myeloma with or without extramedullary involvement. Future studies with long-term follow-up are recommended to further explore these findings. [Table: see text]
First relapse in patients with multiple myeloma: Outcomes and predictors.
Authors: Seth Sukriti , Kapoor Prashant , Buadi Francis , Binder Moritz , Cook Joselle , Dispenzieri Angela , Dingli David , Fonder Amie L. , Gertz Morie A. , Gonsalves Wilson I. , Hayman Suzanne R. , Hwa Lisa , Hobbs Miriam A. , Kourelis Taxiarchis , Leung Nelson , Lin Yi , Muchtar Eli , Warsame Rahma M. , Rajkumar S. Vincent , Kumar Shaji 
Published: June 2024

7558 Background: Survival in patients with multiple myeloma (MM) continues to improve with the newer therapies, but there is no clear evidence of a cure and patients continue to relapse. However, most patients have the most extended period without progression with their first-line therapy, and subsequent therapies often provide a shorter duration of response due to the use of drugs with overlapping mechanisms of action and, more importantly, a shorter first remission, pointing toward more aggressive disease biology. With newer immunotherapies being used at 1st relapse, this may change. We designed this study to explore the natural history of MM after the 1st relapse and define the predictors of outcome after the initial relapse. Methods: We identified all patients in the Mayo Clinic database diagnosed between Jan 2004-June 2019 who had had initial disease progression. The study cohort included 2005 patients. We explored the overall survival (OS) from the time of documented disease progression or the start of second-line treatment in patients who had not met IMWG criteria before second-line therapy. Front-line therapy was grouped into those with either an IMiD or PI, both IMiD and PI, daratumumab with IMiD and PI, and none of these agents. The IMiD and PI were always used with dexamethasone with or without an alkylator. Results: The median age was 63 (range 24-95) years and 60% were male. The median estimated follow-up from diagnosis for all patients was 86 mos. (95% CI; 82, 88) and the median time to progression from the start of therapy was 25 mos. (95% CI; 24, 26). The median OS from the first progression was 45 mos. (95% CI; 42, 50), 36 mos. for those diagnosed before 2009, and 52-53 mos. for those diagnosed later. On univariate analysis, age <70 at 1st relapse, RISS I, novel agents in initial therapy, CR in the first line, diagnosis after 2009, initial remission >18 mos, and initiation of therapy before IMWG progression were all associated with improved OS after 1st relapse (Table). On multivariate analysis, age <70, RISS I, initial remission >18 mos, and initiation of therapy before IMWG progression were all associated with improved OS after 1st relapse. Conclusions: The study provides an estimate of the outcomes and significant predictors of outcomes after 1st relapse in patients with MM. These factors should be taken into consideration when designing clinical trials in this patient population. In particular, these factors identify a high-risk group of patients not always identified by baseline characteristics and should be the focus of future trials. [Table: see text]