tbuckley/cabot-search huggingface dataset:
Real world outcome of patients with multiple myeloma who received bispecific antibodies after CAR-T therapy.
Authors: Radhika Bansal, Andre De Menezes Silva Corraes, Larissa Brunaldi, Tyler B Sandahl, Matthew J. Rees, Suzanne R. Hayman, Moritz Binder, Nadine Abdallah, David Dingli, Joselle Cook, Morie A. Gertz, Prashant Kapoor, Taxiarchis Kourelis, Rahma M. Warsame, Shaji Kumar, Yi Lin
Journal: Journal of Clinical Oncology (2024)

7520 Background: There are 2 CAR-T products and 3 bispecific antibodies (BsAbs) that are FDA-approved for patients (pts) with relapsed, refractory multiple myeloma (MM). Clinical trials experience to date suggests that clinical response of BsAb is less impacted after CAR-T therapy. We examined the outcome of pts who received BsAb in standard-of-care (SOC) practice at Mayo Clinic Rochester. Methods: Retrospective analysis of MM patients who received FDA-approved BsAb at Mayo Clinic, Rochester between 12/2022- 1/2024. IMWG criteria was used for clinical response. Results: Sixty-two patients received BsAbs: 77% (48/62) received teclistamab, and 23% (14/62) received talquetamab. Median age was 62 years (range: 33-81), 60% (37/62) were males, and 45% (28/62) received prior CAR-T. Patients who had prior CAR-T therapy had more prior lines of therapy compared to those who did not. Overall, ORR to teclistamab was 61%, which is comparable to previous studies and other real-world reports. ORR and ≥CR rates were comparable between patients with and without prior CAR-T (Table). Of the 28 pts who received CAR-T before BsAbs, 61% (17/28) received idecabtagene vicleucel, 10% (3/28) were ciltacabtagene autoleucel, and 29% (8/28) on clinical trial. We then compared outcome of BsAb between pts who had relapsed from CAR-T within 1 year (n=21, median PFS: 8.84 months (range, 1.12, 10.84)) or after 1 year (n=7, median PFS: 16.62 months (range, 13.30, 36.20)). At the time of BsAb infusion, pts with who relapsed &lt; 1 year vs ≥1 year post CAR-T had comparable blood counts, ALC, M-protein and involved FLC levels, CRP, ferritin and LDH. BsAb CR/sCR rate was significantly higher in pts with disease relapse ≥1 year compared to &lt;1 year post CAR-T (57% vs 14%, p=0.02). Conclusions: Irrespective of prior CAR-T exposure, BsAb have clinical activity in SOC practice in pts with MM. Our preliminary data suggest that responses to BsAbs are better in pts with late compared to early relapse post CAR-T. Longer follow-up is needed to understand the duration of response. Larger, multi-center studies with longer follow-up will help identify factors that impact BsAb response post CAR-T.[Table: see text]
Effect of daratumumab on light chain reduction in newly diagnosed multiple myeloma with light chain cast nephropathy.
Authors: Juan Esteban Velez-Hernandez, Mateo Mejia Saldarriaga, Mark Bustoros, Roger Niles Pearse, Ruben Niesvizky, Jorge Monge Urrea
Journal: Journal of Clinical Oncology (2024)

7554 Background: Light chain cast nephropathy (LCCN) is present in 16-31% of patients (pts) in newly diagnosed multiple myeloma (NDMM). In pts with an involved serum free light chain (iFLC) &gt;150mg/dL and predominant LC proteinuria, the probability of LCCN is high enough for a clinical diagnosis without the need for kidney biopsy. Early mortality is higher in pts with renal impairment (RI) who did not achieve a renal response (RR), and a rapid reduction in iFLC may predict RR. While the use of bortezomib and dexamethasone (Vd) in upfront therapy has led to marked improvements in outcomes, the optimal regimen is unclear. Methods: We included pts with NDMM and RI (creatinine &gt;2 mg/dL or eGFR &lt;40 ml/min/1.73m 2 ) and a diagnosis of LCCN (iFLC &gt;150mg/dL and light chain proteinuria) at a single center from 2005-2023. Pts with &gt;10% albuminuria or a diagnosis of MGRS or amyloidosis were excluded. Primary outcome was FLC response (iFLC &lt;50mg/dL and &gt;90% reduction, FLC-R) at day 30 (d30). Other outcomes included hematologic response (partial response or better) at d30 and RR (minimal response or better) at d90, based on International Myeloma Working Group criteria. Results: We included 51 pts with characteristics depicted in the table. All pts received therapy with Vd, adding cyclophosphamide (VCd) in 26 (51%), daratumumab (dara, DVd) in 13 (25%), both (DVCd) in 6 (12%) and alone in 6 (12%). At d30, 11 pts (58%) in dara-containing regimens (DVd, DVCd) and 10 pts (31%) in non-dara-containing regimens (Vd, VCd) achieved a FLC-R (p=0.08); dara was associated with higher odds of achieving a FLC-R at d30 (OR 2.9, p=0.03) after adjusting for age, stage and eGFR at diagnosis. At d90, pts receiving dara had a higher rate of RR than those who did not (69% vs 58%, p=0.5); dara was associated with higher odds of a RR at d90 (OR 1.6, p=0.5). After adjusting for age, stage and eGFR at diagnosis, achieving a FLC-R at d30 was associated with higher odds of a RR at d90 (OR 8.9, p=0.02). Conclusions: Prompt reduction of iFLC is an important objective during the early treatment of LCCN in order to achieve a RR, and dara increases the odds of achieving a FLC-R. The use of dara led to higher odds of a RR at d90, but not statistically significant. We confirmed that achieving a FLC-R at d30 was associated with achieving a RR at d90. Our results suggest that the role of a dara should be explored in prospective studies for the upfront treatment of LCCN in NDMM. [Table: see text]
Supplement use habits and perceptions in patients with plasma cell disorders.
Authors: Yan Leyfman, Eliana Schach, Andriy Derkach, Francesca Castro, Jorge Arturo Hurtado Martínez, Ana M. Sahagun Sanchez Aldana, Patricia Alejandra Flores Pérez, Maria Malik, Jennifer M. Ahlstrom, Jay R Hydren, Saad Zafar Usmani, Jun J. Mao, Susan Chimonas, Urvi A Shah
Journal: Journal of Clinical Oncology (2024)

7526 Background: Dietary supplement usage is prevalent among cancer patients in the United States (US), estimated at 70% (Du et al., 2020). For patients with plasma cell disorders (PCDs), there is a strong interest in supplement use. Our 23-question survey aims to understand the perceptions, habits, and knowledge surrounding specific supplements — Vitamin D, omega-3 fatty acids, turmeric/curcumin, and probiotics. Methods: From September 2023 to January 2024, 480 survey responses were collected via HealthTree Cure Hub. Deidentified demographic and survey data were retrieved, and summary statistics were used to evaluate responses. Results: Survey participants were predominantly female (58%), white (78%), aged ≥65 (61%), with a college degree or above (67%), and from the US (90%). While most patients (71%) used supplements pre-diagnosis, there was a 46% increase in supplement use post-diagnosis, where95% used supplements. Most patients obtained supplement information online — including medical media (45%) and myeloma education websites (28%)— and from physicians, such as oncologists (46%) or primary care providers (34%). Patient’s goals for supplement use included immune support (70%), prevention of nutritional deficiencies (54%), or halting cancer progression (38%). Of patients, 63% discussed their supplement use with their physician, with 74% preferring their oncologist’s recommendations. Overall, 91% of patients expressed interest in research on the risks and benefits of supplement use. Conclusions: This survey underscores the unmet need for research on supplements. Despite limited evidence, most survey participants reported an increase in supplement use after being diagnosed with a PCD, primarily interested in their oncologist's recommendations. [Table: see text]
CSF proteomics for predicting response to treatment in patients with primary and secondary central nervous system lymphoma.
Authors: Hannah E. Wilding, Aastha Aastha, Nicholas Mikolajewicz, Leonardo Macedo Filho, Debarati Bhanja, Madison Heebner, Shahbaz Khan, Vladimir Ignatchenko, Ahmad Ozair, Manmeet Singh Ahluwalia, Michael J. Glantz, Thomas Kislinger, Alireza Mansouri
Journal: Journal of Clinical Oncology (2024)

e19083 Background: Despite exquisite responses to initial therapy in patients with CNS lymphoma (CNSL), relapse is common and overall responses are disappointing compared to other non-CNS diffuse large B-cell lymphomas. Incorporation of multi-agent intraventricular chemotherapy (MAIVC) alongside systemic therapy is a novel strategy. To maximize MAIVC benefit, identification of minimally-invasive biomarkers for guiding patient management is necessary. This study sought to identify cerebrospinal fluid (CSF)-based proteomic predictive biomarkers for MAIVC treatment response at baseline and for longitudinal monitoring of tumor burden in CNSL. Methods: A retrospective study of patients with primary or secondary CNSL that were treated with MAIVC at Penn State Health (2015-2021) was conducted and reported following REMARK guidelines. Each MAIVC cycle was administered via Ommaya reservoir and included a 2-drug combination comprised of methotrexate, rituximab, cytarabine, etoposide, topotecan, gemcitabine, or thiotepa. Patient-matched CSF was sampled at pre- and post-therapeutic endpoints and profiled using shotgun proteomics. Patients were grouped by treatment response status. Early responders were defined as patients achieving malignant-cell-free CSF within 6 MAIVC cycles, whereas never responders were those patients that i) did not achieve malignant-cell-free CSF by endpoint or ii) required salvage surgery or radiation during MAIVC. Results: 59 patients were included (21 primary; 38 secondary CNSL) with a median age of 66 years (range 25-90) and median number of MAIVC cycles of 8 (range 2-23). Only 1 required Ommaya removal secondary to infection. A proteomic-based classifier, comprised of SGCE, LCP1 and AGRN, discriminated between early and never responders with AUROC of 0.95. Comparison of CSF at baseline (&lt;3 cycles MAIVC) vs. post-treatment (&gt;12 cycles MAIVC) identified H3F3A, YWHAE, LCP1, CA1 and GAPDH as tumor burden biomarkers. Conclusions: Here we developed a proteomic signature capable of predicting CNSL patient response to MAIVC, with potential to improve clinical decision making. Furthermore, the biomarkers associated with tumor burden represent important indicators of treatment response. Ongoing efforts are underway to evaluate these candidates in independent validation cohorts.
Time to antibiotic administration in patients undergoing HSCT with neutropenic fever.
Authors: Keval Yerigeri, Jennifer Glover, Bushraa Shamshuddin, Tamila L. Kindwall-Keller
Journal: Journal of Clinical Oncology (2024)

e19501 Background: Cytotoxic chemotherapy for hematologic malignancies may adversely affect myelopoiesis, resulting in profound neutropenia that predisposes patients to severe infections. Patients undergoing hematopoietic stem cell transplantation (HSCT) are at particularly increased risk. Neutropenia is defined by an absolute neutrophil count (ANC) &lt;500 cells/μL per complete blood count with differential. Neutropenic fever is a critical event with one-time temperature ≥101ºF or ≥100.4ºF sustained over one hour. Current standard-of-care is to initiate broad-spectrum antibacterial therapy within 30-60 minutes of presentation. MetroHealth Medical Center in Cleveland, Ohio launched a new Blood and Marrow Transplant program in 2023 in the state-of-the-art Glick Center. This retrospective study explores time to blood culture draw and initiation of antibiotics in HSCT patients with neutropenic fever. Methods: The MetroHealth HSCT database was used to identify hematologic malignancy patients status-post HSCT treated in the Blood and Marrow Transplant program. Tumor type and staging, chemo history, and infection prophylaxis (PPx) were recorded from chart review. Neutropenic fever episodes were identified by review of vitals history. Time to blood culture draw and antibiotic administration was then calculated from the medication administration record (MAR). Results: N = 11 hematologic malignancy patients status-post HSCT and chemotherapy were identified in the MetroHealth database. 8 presented with multiple myeloma (RISS stage II – IV), 2 with Hodgkin lymphoma, and 1 with mantle cell non-Hodgkin lymphoma. All patients were on Valtrex or acyclovir PPx, 10 on levofloxacin PPx, and 9 on fluconazole PPx. 6 of 11 patients had one documented episode of neutropenic fever each. ANC levels ranged from unidentifiable to 420 cells/μL. Half of the episodes saw blood culture draw within 1 hour and initiation of antibiotics in 60-90 minutes. The other 3 episodes saw culture draw at 2:13, 3:09, and 10:10 hours from fever and antibiotic administration at 12:00, 2:53, and 10:23 hours, respectively. Infectious disease (ID) specialists were consulted in each of the latter 3 cases. Conclusions: No patient at MetroHealth with neutropenic fever has seen appropriate initiation of antimicrobials within 30 to 60 minutes of presentation. Hypotheses for this delay include improper chart documentation, nurse training (delay in physician notification), and provider comfort (antimicrobials deferred to day team, ID consults). The latter is of particular concern given incidents of &gt;10 hour delay to antibiotic initiation. Fortunately, there have not been any severe morbidity or mortality outcomes yet. Next steps are to deploy a quality improvement initiative to increase speed to fever identification, blood culture draw, and empiric antimicrobial delivery.
Epcoritamab + R-DHAX/C in transplant-eligible patients (pts) with high-risk relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL).
Authors: Yasmin Karimi, Pau Abrisqueta, Sven de Vos, Marcel Nijland, Fritz Offner, Kojo Osei-Bonsu, Ali Rana, Kimberly G. Archer, Yaou Song, Raul Cordoba, Lorenzo Falchi
Journal: Journal of Clinical Oncology (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: Geoffrey Chong, Denise Lee, Sze Ting Lee, Anneke Grobler, Richard Khor, Belinda A. Campbell, Thanuja Thachil, Kate Manos, Arina Martynchyk, Genevieve Douglas, Colm Keane, Jodie Palmer, Eliza Anne Hawkes
Journal: Journal of Clinical Oncology (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 &amp; 15). Pts with &lt; 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 &lt;5/15 CR deemed futile in 1 st 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 &gt;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 &amp; OS is 87% &amp; 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]
Risk of new-onset hypertension in patients (pts) with newly diagnosed chronic lymphocytic leukemia (CLL) treated with Bruton tyrosine kinase inhibitors (BTKi): A real-world data study using the Symphony Health Solution database.
Authors: Tzuyung Douglas Kou, Lili Zhou, Jinzhi Zhou, Aileen Cohen, Wassim Aldairy, William B White
Journal: Journal of Clinical Oncology (2024)

e19014 Background: BTKis provide an important therapeutic option for pts diagnosed with CLL. Concerns have arisen about a potential association with the risk of cardiovascular events with BTKi. Using the Symphony Health Solutions database, this study describes the risk of new-onset hypertension in CLL pts treated with and without BTKis. Methods: Newly diagnosed CLL pts who started ibrutinib or acalabrutinib and those not treated with an approved BTKi between 2019 and 2022 were included in the analysis. The prevalence of hypertension prior to and risk of new-onset hypertension after treatment initiation were defined by use of antihypertensive medication. Pt demographics and comorbidities were described. Multivariate regression and inverse probability treatment weight based on propensity score were used to account for bias due to differences in pt characteristics between groups. Results: In CLL pts treated with (n=7,114) and without BTKis (n=34,571), demographics and clinical characteristics included age at the index date (mean: 70.2 yrs, BTKi; 69.0 yrs, without BTKi), sex (male: 59.8%, BTKi; 55.7%, without BTKi), and Charlson comorbidity scores (mean: 3.3, BTKi; 3.1, without BTKi). At baseline, the prevalence of hypertension defined by the use of antihypertensive medication was 67.8% with BTKi and 67.6% without BTKi. Among pts without any antihypertensive medication use at baseline, the rates of new-onset hypertension within 1 yr after treatment initiation were greater in pts with BTKis than without BTKis (Table). Conclusions: In this real-world analysis, CLL pts treated with BTKis had a higher burden of comorbidities, and use of antihypertensive medication was common. The risk of new-onset hypertension was higher in pts initiated on BTKis than those on non-BTKi treatments. These data suggest that development of hypertension is an important consideration in the long-term management of CLL pts undergoing BTKi treatment. [Table: see text]