tbuckley/cabot-search huggingface dataset:
Risk of gastrointestinal adverse events associated with chimeric antigen receptor T-cell therapy (CAR-T): A nationwide analysis.
Authors: Shahryar Khan, Samia Asif, Mashal Alam Khan, Muhammad Atif Khan, Muhammad Kashif Amin
Journal: Journal of Clinical Oncology (2024)

e19505 Background: Chimeric antigen receptor T-cell therapy (CAR-T) has been successfully used and has improved outcomes in the treatment of B-cell hematological malignancies and multiple myeloma. There is evidence that unique serious adverse events like cytokine release syndrome (CRS) and Immune effector cell associated neurotoxicity syndrome (ICANS) are associated with CAR-T. Gastrointestinal adverse events (GI-AE) are commonly observed after CAR-T, although they are not well characterized. In the analysis, we summarized the incidence of gastrointestinal adverse events (GI-AE) and mortality associated with CAR-T with or without CRS. Methods: We conducted a retrospective cohort study using the 2020 Nationwide Inpatient Sample database, which is the largest nationally representative inpatient database in the United States. The dataset is weighted to obtain national estimates, and ICD-10 was utilized to identify admissions for CAR-T. The primary outcome is in-hospital mortality, and secondary outcomes are GI-AE associated with CAR-T with or without CRS and length of stay (LOS). Odds ratio (OR) and Mean difference (MD) were adjusted for confounders like comorbidities and sociodemographics using multivariate regression analysis. Results: There were 32 million weighted discharges in the 2020 NIS database; a total of 1950 cases were identified receiving CAR-T therapy with a mean age of 56.53, male 60.51%, and white race 74.8%. In our study, 40.25% had GI-AE, 15.38% had CRS and 13.8% had ICANS. The most common GI-AE was nausea and vomiting (23.84%). Other GI-AE were diarrhea (9.5%), colitis (8.2%), peptic ulcer disease (2.9%), hepatic failure (1.28%), and pancreatitis (2.2%). 68 (3.85%) patients died after receiving CAR-T. The results revealed that CAR-T with GI-AE was not significantly associated with in-hospital mortality (adjusted OR = 1.12, 95% CI: 0.29-4.24), and LOS (adjusted mean difference = 3.38, 95% CI: -0.91-7.67) compared to CAR-T without GI-AE. Liver failure is significantly associated with the highest mortality after CAR-T (OR = 46.62, 95% CI: 6.9-315). Conclusions: The national survey reveals that predominantly GI-AE are mild including nausea, vomiting, and diarrhea. GI-AE related with CAR-T had similar outcomes including mortality and LOS compared to CAR-T without GI-AE. The risk of mortality becomes higher when CAR-T complicated by hepatic failure. [Table: see text]
A phase III, randomized study of daratumumab, cyclophosphamide, bortezomib and dexamethasone (DARA-VCD) induction followed by autologous stem cell transplant or DARA-VCD consolidation and daratumumab maintenance in patients with newly diagnosed AL amyloidosis.
Authors: Patrick Hagen, Surbhi Sidana, Terri L. Parker, Brian Keith Walker, Antje Hoering, Vaishali Sanchorawala, Jeffrey A. Zonder, Taxiarchis Kourelis, Anita D'Souza, Heather Jolie Landau, Adam Rosenthal, Sikander Ailawadhi, Robert Z Orlowski
Journal: Journal of Clinical Oncology (2024)

TPS7575 Background: Light chain (AL) amyloidosis is a plasma cell malignancy characterized by the production of amyloidgenic clonal light chains that deposit in various tissues. The addition of daratumumab to bortezomib, cyclophosphamide and dexamethasone (Dara-VCD) has improved depth of hematologic and organ responses. However, this approach has not yet demonstrated an overall survival (OS) benefit with short follow-up. Autologous stem cell transplant (ASCT) consolidation remains safe and is associated with deep and durable hematologic responses with an 83% 2-year progression free survival (PFS) and up to 72% of patients achieving a VGPR or better, comparable to Dara-VCD (79%). In multiple myeloma, ASCT improved PFS even in patients who are MRD negative at the end of standard induction therapy. It is thus reasonable to consider that ASCT might provide similar benefits in AL patients. No randomized data exist to inform the optimal use of ASCT in the era of Dara-VCD. Methods: This randomized phase 3 SWOG led intergroup trial will accrue a total of 143 participants per arm and compare MOD-PFS (major organ deterioration progression free survival: defined as time from randomization to death, cardiac/renal progression, or hematologic progression) between participants receiving an ASCT with those receiving Dara-VCD consolidation following uniform Dara-VCD induction. A median MOD-PFS of 31 months is anticipated in the non-ASCT arm. This study has 90% power and a two-sided significance level of 0.05 to detect a hazard ratio of 0.62 corresponding to a MOD-PFS of 50 months in the ASCT arm. Important additional endpoints include OS, hematological PFS, cardiac and renal responses and progression, MRD negativity both by peripheral blood mass spectrometry and bone marrow next generation flow cytometry, delayed utilization of ASCT, and quality of life. This trial was activated on 12/1/2023. Funding: NIH/NCI/NCTN grants and in part by Janssen Pharmaceuticals. Clinical trial information: NCT06022939 . [Table: see text]
Analysis of real-world (RW) pomalidomide (pom) dosing patterns in patients (pts) with multiple myeloma (MM) from the Flatiron database.
Authors: Binod Dhakal, Amandeep Godara, Eva Medvedova, Seema Naik, Ajay K. Nooka, Trilok V. Parekh, David Hadley, Ankit J. Kansagra, Larry D. Anderson, Jr
Journal: Journal of Clinical Oncology (2024)

e19508 Background: Pom is an immunomodulatory drug commonly used in combination with other antimyeloma therapies for the treatment (tx) of pts with MM. However, there is a paucity of data on RW dosing patterns with pom and associated tx outcomes. We report RW pom dosing patterns and effectiveness using RW data to inform potential pom dosing strategies as part of combination tx regimens. Methods: RW pom data in pts with MM were derived from the US Flatiron Health deidentified electronic health record (EHR) database (Jan 2011–Nov 2021). Pom starting dose (1, 2, 3, or 4 mg) and line of therapy (LOT) were identified from EHRs. Tx patterns were captured per LOT; pts could receive &gt;1 pom-containing tx regimen/LOT. Pts receiving pom were followed until Dec 2023 for outcome analysis. Overall survival (OS) and time to next tx (TTNT) were estimated using the Kaplan-Meier method and analyzed by log-rank testing. Results: Of 15,378 pts with MM, 2,034 had an order for pom, of whom 1,344 received pom and 880 had LOT data. The most common initial pom dose was 4 mg (50%), followed by 2 mg (30%), 3 mg (16%), and 1 mg (4%). The most common pom-containing tx regimens were: daratumumab + pom + dexamethasone (d; 29%), pom + d (18%), and carfilzomib + pom + d (14%); 6% of pts received pom monotherapy. Retreatment with pom was infrequent, with 84% of pts receiving only 1 pom-containing LOT. Most pts (n=652, 74%) remained on the initial pom dose received; of these, 367 pts remained on an initial dose of 4 mg. Among pts who changed dose (n=227, 26%), 36% changed from 2 mg and 36% changed from 4 mg. Of pts who received an initial dose of 4 mg and changed dose (n=81), 43%, 51%, and 6% reduced to 3, 2, and 1 mg, respectively. Of pts who received an initial dose of 2 mg and changed dose (n=82), 17% reduced to 1 mg. Among pts who received an initial dose of &lt;4 mg and changed dose, dose escalation was common (67% of pts with a 3 mg initial dose increased to 4 mg; 33% and 50% of pts with a 2 mg initial dose increased to 3 and 4 mg, respectively). Outcome analysis of pts with LOT and available follow-up data suggest that initial pom dose had no impact on OS and TTNT (Table). Log-rank analysis of OS and TTNT between the initial doses of 2 and 4 mg showed no significant difference among all pts ( P=0.32) or in pts who changed dose ( P=0.29). Conclusions: RW analyses show that most pts remain on the initial pom dose received, but some pts changed doses. Pom, most commonly used in combination regimens, can be used across an initial dose range with no impact on efficacy in pts with MM. Optimal pom dosing may vary across pts and combination regimens; pom dosing should be tailored to pt needs per disease and tx factors. [Table: see text]
Ciltacabtagene autoleucel vs standard of care in patients with functional high-risk multiple myeloma: CARTITUDE-4 subgroup analysis.
Authors: Luciano J. Costa, Katja C Weisel, Niels W.C.J. van de Donk, Surbhi Sidana, Yaël C Cohen, Duncan Purtill, Cyrille Touzeau, Carlos Fernandez de Larrea, Joaquin Martinez-Lopez, Nikoletta Lendvai, Ana Slaughter, Carolina Lonardi, Man Zhao, Katherine Li, Martin Vogel, Mythili Koneru, Nitin Patel, Erika Florendo, Octavio Costa Filho, Maria-Victoria Mateos
Journal: Journal of Clinical Oncology (2024)

7504 Background: Functional high-risk (FHR) multiple myeloma (MM) is associated with poor prognosis. In CARTITUDE-4, a single ciltacabtagene autoleucel (cilta-cel) infusion significantly improved progression-free survival (PFS) vs established standard of care (SC; hazard ratio [HR], 0.26 [95% CI, 0.18–0.38]; P&lt;.0001) in patients (pts) with lenalidomide (len)-refractory MM after 1–3 prior lines of treatment (tx; LOT). This post hoc subgroup analysis of CARTITUDE-4 reports outcomes for pts who received cilta-cel vs SC as second-line tx, including pts with FHR MM. Methods: Pts randomized to cilta-cel underwent apheresis, received PVd or DPd bridging tx, and then cilta-cel infusion (target dose, 0.75×10 6 CAR+ viable T cells/kg) 5–7 d after the start of lymphodepletion. Pts randomized to SC received PVd or DPd until progressive disease (PD). FHR was defined as PD within 18 mo after receiving autologous SCT or the start of initial frontline tx. Efficacy was assessed in randomized pts (intent to treat) and safety in pts who received any part of study tx. Results: 136 pts received cilta-cel (n=68) or SC (n=68) as second-line tx. Of these, 79 had FHR MM (cilta-cel, n=40; SC, n=39). Median PFS was longer among pts who received cilta-cel vs SC as second-line tx including the subset who had FHR MM (Table). Overall survival was immature at the time of this analysis. A greater proportion of pts who received cilta-cel vs SC as second-line tx had an overall response, complete response (CR) or better, minimal residual disease (MRD) negativity, and longer median duration of response (DOR), with similar observations among the FHR subset. Proportion of pts with grade ≥3 TEAEs who received cilta-cel vs SC as second-line tx was comparable (96% vs 96%) including the subset with FHR MM (100% vs 97%). Among pts who received second-line tx, 22 died (cilta-cel, n=11; SC, n=11), 16 of whom had FHR MM (n=7; n=9). Conclusions: In pts with len-refractory FHR MM after 1 prior LOT, cilta-cel improved outcomes vs SC and had a safety profile consistent with the known mechanism of action of CAR-T tx, suggesting cilta-cel may overcome the poor prognosis associated with FHR MM. Clinical trial information: NCT04181827 . [Table: see text]
Clinical features and outcomes of patients with follicular lymphoma grade 3A: A real-world study in single center.
Authors: Xingnong Ye, Wenjuan Yu, Juying Wei, Hongyan Tong, Jie Jin
Journal: Journal of Clinical Oncology (2024)

e19058 Background: Follicular lymphoma (FL) was classified into three grades based on the number of centroblasts (FL1-2, FL3A, and FL3B). Guidelines suggest that FL1-2 should be treated according to the treatment recommendations for classical FL. FL3B is usually treated as diffuse large B-cell lymphoma (DLBCL).There is no consensus yet on the management of FL3A. In order to explore the relationship between clinical features and outcomes of FL3A, we conducted this study. Methods: We conducted a retrospective study of newly diagnosed FL patients who were admitted to our hospital from January 2013 to December 2022. The data were collected from the hospital electronic medical record system, including but not limited to: demographic characteristics, pathological information, clinical features at diagnosis, treatment, and efficacy evaluation. The survival curve was calculated through Kaplan-Meier method and compared with Log Rank test.The prognostic factors of PFS was compared by COX regression analysis. Results: There were 253 FL3A patients admitted, accounting for 27.55% of all FL patients. After screening, a total of 223 FL3A patients were included in this study. Among 223 patients, the male to female ratio was close to 1:1; The median age is 57 years old. At diagnosed, 33 patients in early stage and 190 in advanced stage. Among advanced patients, 144 had no treatment indications according to the GELF criteria. 86.1% (192/223) of patients received systemic treatment, with the majority of rituximab contained regimens. The overall response rate (ORR) was 96%, and 62.9% of patients who responded to chemotherapy received maintenance therapy with CD20 monoclonal antibody. A median follow-up of 41 months, with an estimated 5-year OS of 91.3% and 5-year PFS of 73%. The PFS of advanced FL patients treated with RCHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) was significantly longer than that of non-RCHOP regimen patients (P&lt;0.05). The PFS of patients receiving maintenance treatment was better than that of those not (P&lt;0.05). Conduct prognostic analysis on advanced FL3A patients. Univariate analysis showed that treatment plan selection, maintenance of treatment, PET scan of FDG metabolic maximum uptake value (SUVmax), Ki-67, lactate dehydrogenase (LDH), white blood cell count (WBC), IgA, IgM, all significantly affected PFS; Multivariate analysis shows SUVmax ≥ 15 and platelet count&lt;100 × 109/L and LDH&gt;210U/L are all correlated with poor PFS. Conclusions: This study found that FL3A accounts for 27.55% of all FLs, with a median age of 57 years old and mostly in the advanced stage. FL3A has a long survival period, with a 5-year PFS of 73%. COX regression analysis showed that SUVmax, platelet count, and LDH were all associated with PFS in advanced FL3A patients.Those may explore new clinical prognosis prediction models.
Outcomes of ide-cel in patients with relapsed/refractory multiple myeloma: A single-institution experience.
Authors: Aaron Trando, Farid Ghamsari, Philip Yeung, Caitlin Costello, Ila M. Saunders, Ah-Reum Jeong
Journal: Journal of Clinical Oncology (2024)

e19500 Background: Idecabtagene vicleucel (ide-cel) is a novel CAR T-cell therapy that targets B-cell maturation antigen (BCMA). This single-center retrospective study reports the real-world clinical outcomes of ide-cel therapy in patients with relapsed/refractory multiple myeloma (RRMM) with the additional goal of investigating host predictive factors for therapy performance. Methods: We conducted a retrospective review of adult patients with RRMM who received ide-cel between 2021 and 2023 at University of California San Diego Health and had at least six months of follow-up data available. Data on baseline characteristics, efficacy responses, and adverse reactions (including CRS and ICANS grading per ASTCT) were obtained. Treatment responses were recorded according to the International Myeloma Working Group criteria. Survival analyses were based on Kaplan-Meier and Cox proportional hazards methods. Results: A total of 25 patients with RRMM were included. The median age was 65 (range, 50-79). 48% of patients were male. Patients received a median of six lines of prior therapy with 12% of patients receiving prior BCMA-targeted therapy. Six patients (24%) had confirmed high-risk cytogenetics while twelve patients (48%) had extramedullary disease. The median follow-up was 11.4 months. The objective response rate was 84%; sCR was seen in 56% of patients, VGPR in 16%, PR in 12%, and PD in 16%. Four patients in sCR have since relapsed. Five deaths were observed (20%), all due to progressive disease. Median PFS for the cohort was 13.9 months (95% CI, 9.21 – NR); among responders, PFS was 20.6 months (95% CI, 11.9 – NR). Median OS was NR (95% CI, 19.3 month – NR). The respective PFS and OS at 12 months was 57% (95% CI, 37% – 86%) and 83% (95% CI, 69% – 100%). Of 11 patients who had relapsed/refractory disease to ide-cel, six were alive at time of last follow-up; three are responding to teclistamab, two to talquetamab, and one to radiation. The incidence of CRS and ICANS was 92% (grade 3-4: 4%) and 12% (grade 3-4: 8%), respectively. Univariate and multivariate analysis did not reveal any significant predictive markers of superior PFS or OS, including age, ECOG, mSMART classification, high-risk cytogenetics, extramedullary disease, median number of lines of prior therapy, prior BCMA-targeted therapy, and triple/penta-class refractory disease. Conclusions: Despite our patients having a high median number of prior lines of therapy, our response and toxicity rates were similar to the findings in the current literature, including those observed in the landmark KarMMa-1 trial. We did not find any significant predictive factors of PFS or OS with the caveat of a small sample size. Further research remains necessary to identify potential predictors that may discriminate responders from non-responders, which will improve the application of CAR T-cell therapy in patients with RRMM.
Sex disparities in short-term outcomes among patients with diffuse large B cell lymphoma undergoing chimeric antigen receptor T-cell therapy in the United States.
Authors: Dhruvkumar Gadhiya, Saisree Reddy Adla Jala, Shruti Aggarwal, Hemamalini Sakthivel, Kanwar Bir Singh Dhaliwal, Kamleshun Ramphul, Shivani Sharma
Journal: Journal of Clinical Oncology (2024)

e19062 Background: Chimeric Antigen Receptor (CAR) T-cell therapy, a promising immunotherapy used in various cancers, including Diffuse large B cell lymphoma (DLBCL), can involve multiple complications and the need for medical interventions. Our retrospective study strives to gain up-to-date insight into sex-based differences among DLBCL patients undergoing CAR T-cell therapy. Methods: We focussed on DLBCL patients undergoing CAR T-cell therapy via the 2017-2020 National Inpatient Sample(NIS). The events of complications between males and females were examined via multivariate regression models. Since the ICD-10 code for cytokine release syndrome (CRS) involved cases between October and December 2020, we used samples for that timeline while evaluating that particular complication. Results: Our study involved 3280 adult cases of DLBCL undergoing CAR T-cell therapy, with 1930 (58.8%) males and 1350(41.2%) females. Age differences were seen as females were older(mean age 61.93 vs. 60.40 years, p&lt;0.01). Females also had lower odds of atrial fibrillation (6.7% vs. 14.2%, aOR 0.440, p&lt;0.01) and acute kidney injury (AKI) (10.0% vs. 18.4%, aOR 0.458, p&lt;0.01), while having higher odds of use of invasive mechanical ventilation (5.6% vs. 5.2%, aOR 2.179, p&lt;0.01), events of sepsis (9.6% vs. 7.8%, aOR 1.575, p&lt;0.01), pancytopenia (69.6% vs. 64.0%, aOR 1.454, p&lt;0.01), and cryoprecipitate transfusion (2.2% vs. 1.8%, aOR 2.325, p=0.041) than males. We did not find any statistically significant differences for events of gastrointestinal bleeding (GIB)(aOR 0.866, p=0.636), tumor lysis syndrome(aOR 0.980, p=0.890), acute pulmonary embolism(aOR 1.133, p=0.719), toxic encephalopathy(aOR 1.009, p=0.935), platelet transfusion(aOR 0.994, p=0.976), RBC transfusion(aOR 0.828, p=0.192), or all-cause mortality(aOR 1.829, p=0.064). In addition, while 51.6% of males and 51.7% of females reported CRS, it was not statistically valid (aOR 0.923, p=0.850). Conclusions: The sex of DLBCL patients undergoing CAR T-cell therapy can influence multiple complications, as described in our study. Further research and endeavors aimed to deepen our understanding of our findings will help bring changes in protocols by physicians to improve the quality of care and outcomes of these patients.
Effect of AVM0703 treatment on the limitations of R-CHOP and survival in a model applicable to ABC subtype DLBCL.
Authors: Theresa Deisher, Sandeep Mittal, Spencer Sawas, McKenzie Michiels, Peter Jarzyna
Journal: Journal of Clinical Oncology (2024)

e19060 Background: The current treatment regimen for DLBCL consisting of rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone (RCHOP), is challenged by molecular and prognostic characterization of DLBCL. Activated B-cell (ABC) lymphoma has a significantly worse prognosis (5 yr OS rate: 45% - 56%) than germinal center B-cell (GCB) lymphoma (78% - 80%) after RCHOP treatment. Around 40% of patients ultimately relapse and/or develop primary refractory disease, cardiotoxicity and long-term secondary malignancies. Efforts are being made to improve the RCHOP backbone by including dose intensification and by the addition of new agents to increase the efficacy and reduced toxicity of RCHOP (McKelvey EM Cancer 1976; Wilson WH Blood 2002; Molina TJ JCO 2014; Coiffier B Hematology 2016). AVM0703, an immunomodulatory drug, mobilizes bispecific γδ and inv-TCR double-positive novel T and NKT cells. In a previous study employing an aggressive, immune resistant A20 mouse lymphoma model (Bascuas T J Transl Med. 2016), neoadjuvant AVM0703 was additive/synergistic, when cyclophosphamide/fludarabine (CyFlu) was dosed 3 and 24 hr later, with no additional toxicities. In the present study we combined AVM0703 with RCHOP to evaluate the efficacy in A20 mice model. Methods: 10 week old Balb/c mice were injected with 2x10 6 murine A20 B-cells in the flank and were randomized (1:1 male: female) into 1) Placebo 2) 3 cycles RCHOP 3) 3 cycles AVM0703 (18mg/kg HED) 4) 3 cycles AVM0703+RCHOP, when tumor size reached ~100 mm 3 . Mice who achieved complete remission (CR) were re-challenged at 21-25 wks later. Pre and post re-challenge, presence of memory cells was analyzed using flow cytometer. All mice were monitored continuously as per the IACUC protocol. Results: Mice treated with the combination of AVM0703+RCHOP achieved superior CR compared to RCHOP alone, which was not curative in any mice. In first phase of the study, 3 out of 11 AVM0703 +RCHOP treated mice showed CR after only 1-cycle. In second phase, 2 of 12 mice survived in CR for &gt;150 days after 3 cycles, whereas no RCHOP mice survived beyond 2 cycles. AVM0703+RCHOP treated mice in long-term CR, had memory cells (CD44hi-Cd62low) pre- and post re-challenge, and no A20 engraftment, suggesting strong immunological memory induced by AVM0703+RCHOP. Conclusions: AVM+RCHOP demonstrated anti-tumor activity in A20 lymphoma mice, with reduced toxicity, compared to RCHOP. Larger preclinical studies are underway to confirm the activity of AVM0703+RCHOP against RCHOP resistant ABC DLBCL, and the potential to reduce total RCHOP exposure to only 3 cycles while maintaining or improving efficacy. [Table: see text]