bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of venetoclax-dexamethasone (VenDex) v pomalidomide-dexamethasone (PomDex) in patients (Pts) with t(11;14)-positive relapsed/refractory multiple myeloma [t(11;14)+ RRMM]: Phase 3 CANOVA study biomarker subgroup analysis.
Authors: Bahlis Nizar J. , Popat Rakesh , Beksac Meral , Dimopoulos Meletios Athanasios , Gatt Moshe E. , Gay Francesca , Jo Jae-Cheol , Kapoor Prashant , Kortüm Martin , Ling Silvia , Nagarajan Chandramouli , Suzuki Kenshi , Onishi Maika , Dail Monique , Rossi Emily , Luo Xizhi (Adam) , Arriola Emma Louise , Bueno Orlando Felix , Ross Jeremy A. , Mateos Maria-Victoria 
Published: June 2024

7510 Background: The randomized Phase 3 CANOVA study’s (NCT03539744) primary analysis showed multiple numerically improved efficacy endpoints with VenDex v PomDex, but the primary endpoint of mPFS by IRC was not statistically significant. Here, we report correlative biomarker analyses from CANOVA. Methods: CANOVA is a randomized, global, open-label Phase 3 study of VenDex v PomDex in pts with t(11;14)+ RRMM and ≥2 prior lines of therapy (LOTs). The primary endpoint was mPFS by IRC. Key secondary endpoints included ORR, ≥VGPR, mOS, and MRD negativity (<10-5). In post hoc mPFS sensitivity analysis, disease progression, death, and start of next LOT were defined as events. BCL2 gene expression by RNAseq (3.7 log2 FPKM prespecified median cutoff for BCL2high v BCL2low) and chr1q abnormalities by whole-exome sequencing (normal, gain, or amp) were assessed centrally from pretreatment, CD138-enriched BM aspirates. Results: mPFS, post hoc mPFS, and mOS in the VenDex arm were similar by BCL2 status, with numerically higher ORR, ≥VGPR, and MRD negativity rates in the BCL2highsubgroup. In contrast, mPFS and mOS within the PomDex arm were numerically longer in the BCL2lowsubgroup, despite equal ORR in both subgroups (Table). Presence of 1q abnormalities was evenly distributed across BCL2high v BCL2low subgroups in the VenDex arm (51% v 45%) but not in the PomDex arm (59% v 31%). Normal 1q and gain(1q) subgroups had numerically improved mPFS, mOS, ORR, ≥VGPR, and MRD negativity with VenDex; pts with amp(1q) had poor outcomes regardless of treatment, albeit the sample size was small. Conclusions: Pts with BCL2high or gain(1q) had numerically improved clinical efficacy with VenDex v PomDex. Clinical benefit was consistent across BCL2 subgroups ( BCL2high or BCL2low) with VenDex but not PomDex. Pts with amp(1q) fared poorly irrespective of treatment arm. Clinical trial information: NCT03539744 . [Table: see text]
Characterization of the BCMA epitope bound by BCMA-CD3 T cell engager elranatamab.
Authors: Josic Maria , Schweibold Reece , Mosyak Lidia , Chaparro-Riggers Javier , Baaten Bas , Bompiani-Myers Kristin 
Published: June 2024

7546 Background: Elranatamab is a BCMA-CD3 bispecific antibody with an accelerated approval in the US and EU for relapsed/refractory multiple myeloma (RRMM). Elranatamab binds to CD3 on T cells and BCMA on MM tumor cells; this dual binding results in T cell activation, cytokine release, and tumor cell killing. Engagement of the BCMA surface receptor by its ligands, APRIL and BAFF, mediates plasma cell proliferation and survival. Elevated BCMA, as well as BAFF and APRIL are present in MM patients, yet in vitro functional assays have shown physiologically relevant soluble APRIL or BAFF concentrations did not significantly impact elranatamab activity. Moreover, emerging clinical data from relapsed patients has identified novel, yet relatively rare BCMA protein mutations that may impact BCMA ligand or targeted modality binding. Here we characterized the BCMA binding affinity, evaluated the impact on BCMA binding to BAFF and APRIL interactions, and identified the BCMA binding epitope. We also generated a model from crystal structure data to map reported BCMA mutations identified in patients. Methods: Elranatamab binding affinity to recombinant human BCMA and characterization of BAFF and APRIL interactions with elranatamab-bound BCMA were calculated via SPR at 37˚C with a classical sandwich format. The elranatamab BCMA binding epitope was identified by a co-crystal structure with a parental anti-BCMA Fab that has identical CDR sequences to elranatamab. Alpha-fold modeling was used to map identified BCMA mutations on the antibody/BCMA interface. Results: Elranatamab binds to BCMA with higher affinity (~38 pM) compared to reported binding affinities of BAFF (μM range) and APRIL (nM range) ligands. The identified elranatamab epitope largely overlaps with known ligand epitopes, supporting that elranatamab higher affinity BCMA binding blocks ligand binding. Alpha fold modeling of four recently reported rare BCMA mutations shows that they lie along the binding interface. Conclusions: Due to its high affinity for BCMA, elranatamab potency is unlikely to be impacted by elevated levels of soluble BAFF or APRIL in RRMM patients. Future studies are needed to characterize the impact of emerging MM patient BCMA mutations on the binding and function of anti-BCMA targeting modalities, particularly given the small extracellular domain of BCMA available for therapeutic targeting and the highly overlapping binding epitopes reported for approved BCMA agents.
The association between osimertinib and nutritional deficiency among patients with non-small cell lung cancer.
Authors: Tang Zhiting , Chiang Cho Han , Chang Yu-Cheng , See Xin Ya , Wang Qian , Dowlati Afshin , Chiang Cho Hung , Chi Kuan-Yu 
Published: June 2024

8031 Background: Osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), is the standard-of-care in EGFR mutation-positive non-small-cell lung cancer (NSCLC) in various settings. Osimertinib commonly causes gastrointestinal adverse effects thereby potentially leading to nutritional deficiencies. Therefore, we aim to evaluate the association between the use of osimertinib and nutritional deficiencies among patients with NSCLC. Methods: We performed a retrospective, propensity score matched study using the TriNetX database, a network comprising deidentified data across more than 120 participating healthcare institutions. We included patients with NSCLC who received either osimertinib or other EGFR-TKIs (afatinib, dacomitinib, erlotinib, gefitinib). The outcomes of interest included vitamin B deficiency, vitamin D deficiency, iron deficiency as well as associated anemia including vitamin B12 deficiency anemia, folate deficiency anemia, and iron deficiency anemia within 5 years of EGFR-TKI initiation. Results: We matched 4264 patients who received osimertinib to patients who received other EGFR-TKIs. In Cox proportional hazard analysis, osimertinib was associated with a 50% higher risk of vitamin B deficiency (Hazard ratio, 1.52 [95% CI: 1.07-2.16]) compared to other EGFR-TKIs. Consistent with this observation, osimertinib was associated with an increased risk of vitamin B12 deficiency anemia and a tendency towards folate deficiency anemia. We also noted a 2-fold higher risk of vitamin D and 5-fold higher risk of iron deficiency in the osimertinib cohort. Consistent with this observation, osimertinib was associated with an increased risk of iron deficiency anemia compared to other EGFR-TKIs. Conclusions: The use of osimertinib is associated with a higher risk of nutritional deficiencies and associated anemias compared to other EGFR-TKIs. One potential explanation is the extended duration of osimertinib therapy, driven by its potent anti-cancer effects. Therefore, it is advisable to consider screening for specific nutritional deficiencies in individuals receiving osimertinib therapy. [Table: see text]
Updated results from COAST, a phase 2 study of durvalumab (D) ± oleclumab (O) or monalizumab (M) in patients (pts) with stage III unresectable non-small cell lung cancer (uNSCLC).
Authors: Aggarwal Charu , Martinez-Marti Alex , Majem Margarita , Barlesi Fabrice , Carcereny Enric , Chu Quincy S. , Monnet Isabelle , Sanchez Alfredo , Dakhil Shaker R. , Camidge David Ross , Pillet Marine , Brown Miranda , Dowson Adam , Cooper Zachary A. , Kumar Rakesh , Herbst Roy S. 
Published: June 2024

8046 Background: D consolidation after concurrent chemoradiotherapy (cCRT) improves survival in pts with uNSCLC. Rational immunotherapy combinations may further improve outcomes. As radiotherapy can induce expression of CD73, HLA-E (NKG2A ligand), and PD-L1 in tumor cells, all of which suppress antitumor immunity, there is a rationale for blockade of these immune checkpoints after cCRT. Interim results from COAST (NCT03822351), a global, open-label, Phase 2 study of D ± M (anti-NKG2A) or O (anti-CD73) as consolidation therapy in pts with Stage III uNSCLC, suggested improved progression free survival (PFS) with D+O and D+M vs D alone. We present updated efficacy and safety. Methods: Pts with histologically / cytologically documented Stage III uNSCLC and ECOG PS 0 / 1 with no progression after cCRT were randomized (1:1:1; stratified by histology) within 42 days post cCRT to receive D 1500 mg IV every 4 weeks (Q4W) for 12 months ± O 3000 mg IV Q2W for two cycles then Q4W or M 750 mg IV Q2W. Primary endpoint: objective response rate (ORR). Key secondary endpoints: safety, PFS, and overall survival (OS). Results: From Jan 2019 to Jul 2020, 186 of 189 randomized pts received treatment. Baseline characteristics were generally balanced across arms. As of Jul 18, 2023, median follow-up was 30.1 mo (range, 0.4–48.9). Of pts receiving D, D+O, and D+M, 69.7%, 44.1%, and 41.0% discontinued treatment (Tx), primarily due to progressive disease (42.4%, 18.7%, and 19.6%) or adverse events (AEs; 15.2%, 15.3%, and 14.8%). Median exposure was 7 cycles (range, 1–13) for D, and 13 (1–13) for D+O and D+M. ORR, PFS, and OS (39.6% maturity) are summarized in the Table. Tx-emergent AEs occurred in 98.5%, 96.6%, and 100% (Grade [G] 3/4: 34.8%, 33.9%, and 32.8%) of pts receiving D, D+O, or D+M, respectively; immune-mediated AEs (imAEs) occurred in 34.8%, 25.4%, and 34.4% (G 3/4: 3.0%, 0%, and 3.3%); and the AE of special interest pneumonitis occurred in 16.7%, 20.3%, and 18.0% (G 3/4: 0%, 0%, and 1.6%). Subgroup analyses and biomarker data will be presented. Conclusions: D+O and D+M increased ORR and prolonged PFS and OS vs D alone. Safety was similar across arms, with no new safety signals. Further investigation of D, D+O, and D+M in this population is ongoing in the Phase 3 PACIFIC-9 study (NCT05221840). Clinical trial information: NCT03822351 . [Table: see text]
Prospective monitoring for immunotherapy by liquid biopsy and signal pathway alterations in head and neck cancers.
Authors: Kano Yoshihito , Noji Rika , Naito Takahiro , Fujiwara Shun , Ikeda Sadakatsu , Mori Takehiko , Harada Hiroyuki , Suenaga Mitsukuni 
Published: June 2024

e18000 Background: Clinical biomarkers that predict response or prognosis to immune checkpoint inhibitors (ICIs) are unclear in head and neck squamous cell carcinoma (HNSCC). Comprehensive genome profiling (CGP) testing including liquid biopsy using cell-free DNA (cfDNA) has become clinically available; however, CGP testing is approved only once per patient under the Japanese health insurance system. Therefore, whether liquid biopsy is useful for detecting sequential genetic change and disease progression as a real-time monitoring tool is still unknown. This study aims to analyze the cfDNA in the plasm of recurrent or metastatic (R/M) HNSCC patients during ICI therapy. This study was prospectively conducted to examine the relationship between sequential genetic changes and treatment response. Methods: In this prospective study, we examined ten evaluable R/M HNSCC cases treated with ICI monotherapy (nivolumab or pembrolizumab) from October 2020 to December 2023. Blood samples were collected and analyzed using Guardant360 at differing three-time points (0, 4, and 24 weeks or at progressive disease, PD). Results: The ten cases consisted of 5 males and 5 females, with a median age of 71 years old (52-92 years old). Seven patients received pembrolizumab as a first line and three received nivolumab as the second line treatment. The best response to ICI was partial response (PR) in 3 cases , stable disease (SD) in 1 and PD in 6. Three cases discontinued the study at the second point because of the rapid disease progression. Microsatellite status is stable in all cases. Eight of the ten cases had at least one pathogenic mutation, one case had only variants of unknown significance, and one case that had target lesions at lung metastases had none of them through a series of liquid biopsies. The most frequent gene alterations observed were TP53 (60%), TERT promoter (20%), GNAS (20%), and EGFR amplification (20%). In particular, EGFR amplification had emerged at the second point in two PD cases and these patients showed the sensitivity to cetuximab-based therapy at the following treatment line. In all PD cases, the highest variant allele fraction (VAF) was increased at the second point, which might help predict the response to ICI therapy. In one case achieving PR, BRAF mutation had emerged at the second point. Then it was undetectable at the third point with PD, and GNAS mutation was newly detected. In another case, APC inactivation had disappeared at the second point with PR, even though GNAS mutation emerged, and this case maintained the response to ICI. These results suggest that switching the signals in the MAPK or Wnt pathway could impact the response to ICI therapy. Conclusions: The findings of this prospective study demonstrated that the highest VAF alterations and genetic mutations detected by cfDNA analysis could reflect and predict the response to ICI.
A multicenter, retrospective study analysis: Evaluating the efficacy and safety of pembrolizumab in the first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma.
Authors: Hu Man , Zhang Shichuan , Han Yaqian , Wu Hui , Gao Jin , Wu Haijun , Lin Qin , Shang Wei , Li Xia , Feng Hong , Qiao Qiao , Hu Guangyuan , Yang Kunyu , Song Xicheng , Cao Yuandong , Kang Min , Wang Ruozheng , Yu Jinming 
Published: June 2024

e18013 Background: PD-1-based therapy has become the first-line standard treatment for R/M HNSCC, but KN-048 lacked data on the mainland Chinese population. This study aims to conduct a pooled analysis of the efficacy and safety of first-line pembrolizumab-based therapy in patients (pts) with R/M HNSCC from different regions in China. Methods: Data comes from 17 hospitals. R/M HNSCC pts who received pembrolizumab alone or in combination with chemotherapy/targeted therapy from July 2020 to Jan 2023 were reviewed by searching the hospital HIS/medical record system. The primary endpoint of was OS, and secondary endpoints include time of pembrolizumab treatment (TOPT), safety, etc. Investigators also explored the impact of different biomarkers on survival. This study used SPSS 29 to analyze the data. Results: Total 160 pts were included. Median age was 60 yrs. 81.2% of pts was male, 95% of pts had an ECOG 0-1 . Main primary tumor site showed: oral cavity (60.6%), larynx (12.5%), oropharynx (10.6%). 88.8% of pts had undergone surgery in the past, and 65% received RT. The proportion of pts with only recurrence reached 75.6%. 79 (90.8%) had CPS of 1 or more and 44 (50.6%) had CPS of 20 or more. Other baseline information could be seen in the table. The median follow-up time was 18.5 mos. 70.6% of pts received pembrolizumab combined with chemotherapy, 17.5% received pembrolizumab alone. 48 pts subsequently received second-line treatment, more than half of which were target-based treatments. The median OS of all pts was not reach, among which the mono group vs. combination chemotherapy group (p=0.254). 18mo-OS of monotherapy was 69%, while 61% in combination. No statistical difference was seen in mTOPT (6.0 vs 4.7 mos, p=0.644). The results of the Cox Proportional Hazards Model suggest that ECOG score, smoking history, previous RT and distant metastatic of tumors were related to OS. Primary tumor location, T stage, EGFR mutation related to TOPT. Studies have not found a significant correlation between CPS and survival prognosis. 28.1% of pts experienced TRAEs, the most common of which was G1-4 myelosuppression (33.3%). The main TRAEs of G3-4 were pneumonia (11.1%), bone marrow suppression (8.9%) and abnormal liver function (4.4%). No patient died due to TRAEs. Conclusions: The data reflects that the real-world mOS with local recurrence as the main population was significantly higher than KN-048, and some clinical indicators related to prognosis were also found. In the future, the data of pembrolizumab in R/M HNSCC will be further explored to find more valuable biomarkers. [Table: see text]
Clinicians' perspectives of barriers and facilitators of suicide screening in head and neck cancer care.
Authors: Osazuwa-Peters Nosayaba , Mwobobia Judith , Fish Laura J. , Falkovic Margaret , Benvenisti Revital , Lee Walter T. , Brownson Ross , Rosenstein Donald L. , Goldston David B. 
Published: June 2024

e18023 Background: Patients with head and neck cancer (HNC) face a heightened risk of suicide, surpassing rates in other cancers and the general population. Unfortunately, there are currently no suicide-specific clinical guidelines in oncology, and it is unclear what barriers and facilitators impact suicide screening initiatives in HNC care. This qualitative study explored experiences, barriers and facilitators of suicide screening and management of mental health concerns in a diverse group of HNC clinicians. Methods: We conducted qualitative interviews with 16 HNC clinicians at a single healthcare system, including head and neck surgeons, radiation oncologists, medical oncologists, and nurses/nurse practitioners/physician assistants. Interviews covered topics such as clinicians’ perspective of the impact of HNC on patients’ mental health, experience with suicide risk assessment, existing protocols, and overall experiences related to managing mental health concerns in patients with HNC. Using rapid analysis techniques, we identified common challenges, facilitators, and training needs. Results: Our study uncovered distinct barriers faced by HNC clinicians. Key themes included the notable absence of formal suicide and mental health training among HNC clinicians; critical gaps in clinician education and the lack of established protocols for appraising and managing mental health concerns, particularly those related to suicide risk. Other barriers identified included clinicians’ uncertainties in recognizing and addressing suicidal thoughts, limited familiarity with available screening tools, and insufficient resources for patient support. Some key facilitators also emerged, including longer clinic visit times, mental health discussions in interdisciplinary conferences, and greater accessibility of mental health services for comprehensive patient support. Conclusions: In this qualitative study, we observed important barriers in mental health support and service delivery for HNC patients, especially gaps in clinician training, and lack of knowledge of existing suicide-related protocols. Given the suicide burden in HNC, it is important to address these challenges and begin developing initiatives for clinician training and formalized protocols to enhance mental health care for HNC patients.
A nationwide analysis of inpatient mortality for patients with leukemia with iron deficiency anemia.
Authors: Adegbite Benjamin Olufemi , Cytryn Lawrence 
Published: June 2024

e18521 Background: Leukemia consists of multiple diverse disorders which confer varying morbidities and an increased risk of mortality. Iron deficiency anemia (IDA) is much more common, and while non-malignant, has also been shown to have an association with increased mortality. Despite the probability of these two hematological conditions coexisting, the interaction between them has yet to be closely studied. This retrospective cohort study aims to help elucidate how IDA affects mortality in patients with leukemia. Methods: Data was obtained from the 2017 – 2019 versions of the National Inpatient Sample (NIS) database from the Healthcare Cost and Utilization Project (HCUP) using ICD-10 codes. Patients with all forms of leukemia were identified and then placed into 4 categories: acute myeloid leukemia (AML), acute lymphocytic anemia (ALL), chronic myeloid leukemia (CML), and chronic lymphocytic leukemia (CLL). Lastly, a multivariate regression model was used (adjusted for age, sex, race, median household income based on patient ZIP code, Charleston Comorbidity Index score, hospital region, hospital teaching status based on rural/urban setting) to calculate the adjusted odds ratio (aOR) for the association between the presence of IDA and inpatient mortality. A significance level of p < 0.05 was used throughout. Results: The sample population consisted of leukemia patients with or without IDA. In total, there were 162,873 patients with all ICD-10 coded forms of leukemia, with 5,710 (3.51%) having IDA. Furthermore, this cohort was found to be older than non-IDA leukemia patients (71.1 ± 0.45 years and 59.2 ± 0.71 years with p < 0.05, respectively). With inpatient mortality as the outcome, the multivariate regression analysis performed for the entire sample showed that the odds of mortality while having IDA was 0.65 times that of not having IDA (95% CI 0.56 – 0.76, p < 0.001). When the analysis was then applied to each of the 4 leukemia categories, the IDA cohort still had lower odds of mortality with CLL (aOR 0.73, 95% CI 0.56 – 0.96; p = 0.024). Conclusions: The analyses show that iron deficiency anemia was generally not associated with increased mortality among leukemia patients, particularly those with CLL. This seemingly counterintuitive result warrants further research to confirm these findings and explore possible underlying mechanisms.