tbuckley/cabot-search huggingface dataset:
Frontline brentuximab vedotin and CHP (A+CHP) in patients (pts) with peripheral T-cell lymphoma with less than 10% CD30 expression: Results from the phase 2 SGN35-032 study.
Authors: Swaminathan Padmanabhan Iyer, Deepa Jagadeesh, Eva Domingo-Domenech, Fabio Benedetti, Antonia Rodriguez Izquierdo, Krimo Bouabdallah, Umberto Vitolo, Tim M. Illidge, Jingmin Liu, Eeman Shaikh, Steven M. Horwitz
Journal: Journal of Clinical Oncology (2024)

7069 Background: Brentuximab vedotin (BV), an anti-CD30 antibody-drug conjugate, combined with cyclophosphamide, doxorubicin, and prednisone (A+CHP) was evaluated in the phase 3 ECHELON-2 trial in pts with anaplastic large cell lymphoma (ALCL) and other peripheral T-cell lymphoma (PTCL) types with ≥10% CD30 expression. Compared to conventional frontline therapy, pts treated with A+CHP had a 30% risk reduction in progression-free survival (PFS) (stratified HR=0.70 [95% CI: 0.53, 0.91], P=0.0077) and a survival benefit (HR=0.72 [95% CI: 0.53, 0.99], P=0.0424) (Horwitz 2022). Since no correlation between CD30 expression and duration of response (DOR) was found, it was hypothesized that frontline A+CHP may also be active in pts with non-sALCL PTCL with &lt;10% CD30 expression. Methods: SGN35-032 (NCT04569032; EudraCT 2020-002336-74) is an ongoing phase 2 study. Pts with newly diagnosed non-sALCL PTCL with &lt;10% CD30 expression (by local assessment) are enrolled. Pts are assigned to CD30 &lt;1% or CD30 1% to &lt;10% cohorts. All pts receive 21-day cycles of A+CHP (BV 1.8 mg/kg, cyclophosphamide 750 mg/m 2 , doxorubicin 50 mg/m 2 by IV infusion, and prednisone 100 mg po qd on Days 1-5) for up to 6-8 cycles. The primary endpoint, overall response rate (ORR), is assessed by blinded independent central review (BICR) per Cheson 2007. Secondary endpoints are complete response (CR) rate, PFS, overall survival (OS), DOR, ORR per BICR using modified Lugano, and safety. Results: Seventy pts received ≥1 dose of study drug as of June 30, 2023. Median age was 63.5 years, 57% were male, and 90% had ECOG ≤1. Most had stage IV disease (63%) and were in the CD30 1% to &lt;10% cohort per local CD30 (55%). Median treatment duration was 18 weeks (range, 0-24 weeks). Per BICR, ORR was 77% (95% CI: 65.3%, 86.7%), including 65% (95% CI: 52.4%, 76.5%) with CR among the 66 efficacy evaluable (EE) pts. ORR and CR rate per BICR are listed by cohort in the Table. Grade ≥3 treatment-emergent adverse events (TEAEs) were experienced by 43 pts (61%), most commonly neutropenia (20%), febrile neutropenia (17%), and anemia (10%). Six pts (9%) discontinued treatment due to TEAEs. Nineteen pts (27%) had BV-related serious TEAEs. There were 2 (3%) treatment-related deaths: 1 pt died of decreased appetite and 1 pt died of general physical health deterioration. Conclusions: In pts with non-sALCL PTCL with &lt;10% CD30 expression, A+CHP as frontline therapy appears effective and has a safety profile consistent with label. Clinical trial information: NCT04569032 . [Table: see text]
Outcomes and prognostic factors of patients diagnosed with relapsed/refractory primary B-cell lymphoma: A retrospective study.
Authors: Henry Dumke, Tycel Jovelle Phillips, Mark S Kaminski, Shannon Carty, Ryan A. Wilcox, Dahlia Sano, Malathi Kandarpa, Avery Polk, Yasmin Karimi
Journal: Journal of Clinical Oncology (2024)

7081 Background: PMBCL is an aggressive form of large B-cell lymphoma (LBCL) but has a unique gene expression profiling signature that more closely resembles Hodgkin’s lymphoma. Treatment of R/R PMBCL is largely extrapolated from trials in LBCL with few PMBCL patients included. Randomized trials leading to use of CART as second line treatment for patients with primary refractory or early relapsed LBCL enrolled ≤ 10% PMBCL patients (ZUMA-7 and TRANSFORM). In the rituximab era, there is a paucity of data on the efficacy and outcomes of salvage therapy followed by high-dose chemotherapy and autologous stem cell transplant (HDT/ASCT) in PMBCL. Methods: We conducted a retrospective study of patients with PMBCL, histologically confirmed at the University of Michigan, diagnosed between 2001 and 2023. Results: 70 patients were included with a median age of diagnosis of 31.5 years and 57% female. R-DA-EPOCH was the most commonly used first line therapy (FLT) in 58 patients (83%). 10 patients (14%) were treated with R-CHOP with or without consolidative radiation. 65 patients had end of treatment (EOT) PET/CT: 45 (69%) patients achieved a Deauville (D) 1-3 response, 15 (23%) had D4 response, 5 (8%) had D5 response. 4 (26%) of patients with D4 response and all patients with D5 response ultimately developed R/R disease. 5 had EOT response assessed by CT and all deemed to have complete response. 16 patients (23%) developed R/R disease with a median time to relapse of 8.3 months. All relapses occurred within 2 years: 5 patients with primary refractory disease, 10 patients with relapse &lt;12 months and only 1 patient with relapse &gt;12 months. Platinum based chemotherapy with RICE, RDHAP or RGemOx were the most common salvage regimens (N=11) with ORR 60% among evaluable patients. 5 patients received HDT/ASCT with ORR of 80% and CR rate of 80%. Only 1 patient progressed following ASCT, who had relapsed &gt;12 months after FLT. 9 patients (13%) had high-risk extranodal disease (EN) such as renal, adrenal or breast sites with 2 patients (11%) developing CNS relapse. At a median follow up time of 6.5 years, 5-year PFS and OS for the entire cohort was 76% and 96%, respectively. For patients with R/R disease, 5-year PFS and OS was 49% and 84%, respectively. Conclusions: We report high response rates to platinum-based salvage chemotherapy in the rituximab era, even with primary refractory or early relapsed disease. Higher PFS and OS suggests improved outcomes with HDT/ASCT compared to historical outcomes in R/R LBCL (SCHOLAR-1). Larger prospective studies are needed to determine whether HDT/ASCT or CART is the optimal approach in R/R PMBCL. [Table: see text]
Carfilzomib plus rituximab, ifosfamide, carboplatin and etoposide (C-RICE) led to higher response, OS, and PFS in patients with transplant-eligible relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL).
Authors: Mody Amin, Alex Niu, Kristopher Attwood, Anthony George, Farhan Azad, Jerry Wong, Grant Schofield, Dorothy C. Pan, Sheila N. J. Sait, Anne Marie W. Block, Eugene Przespolewski, Carolyn Connors, Joseph Demarco, Keryn Gauch, Nikolina Gjorgievski, Michael Johnson, Linda Manth, Kenneth McWhite, Matthew Joseph Cortese, Francisco J. Hernandez-Ilizaliturri
Journal: Journal of Clinical Oncology (2024)

7042 Background: The CORAL study highlighted the need to develop novel salvage regimens for R/Rr/r DLBCL previously treated with R+CHOP. Overall response rate (ORR) to second line immuno-chemotherapy was 51% with a 3-year progression free survival (PFS) of 30% following high-dose chemotherapy and autologous stem cell support (HDC-ASCS). Optimal disease control (complete remission [CR] or partial remission [PR]) prior to HDC-ADCS and more recently to chimeric antigen receptor T-cell therapy (CAR T), correlates with improved outcomes. Dysregulation of Bcl-2 family members has been associated with acquired resistance to rituximab and chemotherapy which we have previously shown may be mitigated by co-treatment with proteasome inhibition in pre-clinical model. Subsequently, we conducted a Phase I/II clinical trial evaluating the safety and efficacy of CRICE as salvage therapy for R/R DLBCL (Blood Adv. 2023 7:1146-1155). Methods: Here we retrospectively compared the clinical outcomes of R/R DLBCL patients treated with CRICE (N=28) versus RICE (N=38) on our prior clinical trial (NCT01959698). Demographic, clinical, and pathological characteristics were collected for both groups (Table). Study endpoints consisted of differences in overall response rate (ORR), CR/PR rates, median progression free survival (PFS) and overall survival (OS) between the two cohorts. Results: The addition of Carfilzomib to RICE resulted in improved clinical outcomes. A higher ORR (92.9 vs 76.3, P=0.073) and CR rates (82.1 vs. 44.7, P=0.002) were observed in CRICE vs. RICE treated patients. Multivariate analysis confirmed the higher CR rates in CRICE vs. RICE when adjusted by DLBCL subtype (GCB vs. nNon-GCB, P=0.003). More CRICE patients proceeded to HDC-ASCS (52.6% vs. 47.4%, P=0.618). The 3yr PFS rate was higher in CRICE (54%, 32-72%) vs. RICE treated patients (35%, 19-51%). While the median PFS was longer in CRICE treated patients 36.8m (0.8, 73.2) vs. 3.2m (0.5, 54.2) (RICE), it did not reach statistical significance (P=0.714). No differences in OS were observed between CRICE &amp; RICE patients, median OS 67.3m vs. 71.8m. Conclusions: The CRICE outcomes were more striking in patients with non-GCB r/r DLBCL (ORR 85%, mPFS and OS not reached). CRICE led to high CR rates and longer PFS among r/r DLBCL patients, especially in non-GCB DLBCL patients. CRICE could be an attractive regimen to achieve disease control in r/r DLBCL patients undergoing consolidation therapy with HDC-ASCT or CAR T-cell therapy. [Table: see text]
P-GEMOX with sequential or sandwiched radiotherapy for early-stage extranodal natural killer/T-cell lymphoma.
Authors: Mixue Xie, Qi Jiang, Feng Zhao, De Zhou, Hongyan Tong
Journal: Journal of Clinical Oncology (2024)

7075 Background: Combined modality therapy (CMT), namely chemotherapy combined with radiotherapy, has been recommended for patients with localized extranodal natural killer/T-cell lymphoma (ENKTL). However, the optimal CMT has not been fully clarified. As chemotherapy is more easily accessible than immediate radiotherapy in the routine clinical practice, the “chemotherapy-first” CMT including sequential or sandwiched radiotherapy deserves further exploration. In addition, the optimal non-anthracycline-based regimen needs to be confirmed. Methods: The P-GEMOX regimen was administrated as follows: pegaspargase 2000 IU/m2 intramuscular on day 1, gemcitabine 1000 mg/m2 intravenous on day 1 and 8, oxaliplatin 130 mg/m2 intravenous on day 1 and was repeated every 21 days. Patients who achieved at least stable disease (SD) subsequently underwent involved field radiotherapy (IFRT). The dose of IFRT ranged from 50 to 55 Gy. Performing sequential radiotherapy (4 cycles of CT+RT) or sandwich radiotherapy (2 cycles of CT+RT+2 cycles of CT) is determined by the clinician based on the patients' conditions. The primary endpoint was the overall response rate (ORR) after 2 cycles of chemotherapy, and secondary study endpoints were CR, PFS, and OS. Safety was also evaluated. Results: From August 2020 to April 2023, thirty-seven patients (23 men, 14 women; median age: 55, 26-76 years) with stage I/II ENKTL who had received P-GEMOX were collected. 14 patients were stage IE and 23 were IIE. ALL patients completed at least 2 cycles of P-GEMOX, which resulted in 94.6% (35/37) of ORR including 30 patients with CR and 5 patients with PR. Among the patients in remission, 15 patients received sequential radiotherapy, 15 received sandwich radiotherapy, 4 were waiting for or in the process of radiotherapy, and 1 patient progressed before radiotherapy. With a median follow-up of 14.8 months (range: 2.6-38.1 months), the 3-year PFS and OS were 87.2% (95%CI 69.3%-95%) and 90.6% (95%CI 72%-97.1%), respectively. Sandwich radiotherapy had an obvious trend for longer PFS than sequential radiotherapy (18moths-PFS 100% vs. 78%; P=0.073). During the treatment, 21.6% (8/37) of the patients experienced grade 3–4 treatment-emergent adverse events (TEAEs). The most grade 3–4 hematological TEAEs were neutropenia (7/37, 18.9%) and thrombocytopenia (4/37, 10.8%). As for grade 3–4 non-hematological TEAEs, elevated aminotransferase, hyperbilirubinemia and hypofibrinogenemia were 16.2%, 10.8% and 8.1%, respectively. The adverse events of this CMT were well-tolerated and manageable. No treatment-related death occurred. Conclusions: Our study demonstrated that CMT consisted of P-GEMOX showed favorable efficacy with acceptable toxicity, and sandwich radiotherapy (CT+RT+CT) seems give more favorable PFS than sequential radiotherapy. The CMT protocol could be an effective treatment option for early-stage ENKTL patients.
Extended follow-up results beyond 2.5 years from the pivotal NHL-1 EPCORE trial: Subcutaneous epcoritamab monotherapy in patients with relapsed/refractory large B-cell lymphoma (R/R LBCL).
Authors: Yasmin Karimi, Catherine Thieblemont, Hervé Ghesquieres, Chan Y Cheah, Michael Roost Clausen, David Cunningham, Wojciech Jurczak, Kim M. Linton, Martin Hutchings, Tycel Jovelle Phillips, Umar Farooq, Won Seog Kim, Minh H Dinh, Jagannath Ghosh, Rajash Pallai, Monica Wielgos-Bonvallet, Christian Eskelund, Pieternella Lugtenburg, Julie Vose
Journal: Journal of Clinical Oncology (2024)

7039 Background: Epcoritamab induces high complete response (CR) and MRD-negativity rates with manageable safety in patients (pts) with challenging-to-treat R/R LBCL as shown in the pivotal phase 2 study (NCT03625037). Here we present long-term data, an additional efficacy analysis from the expansion cohort, and data from the cycle 1 optimization (C1 OPT) part. Methods: Adults with R/R CD20 + LBCL and ≥2 prior systemic therapies received subcutaneous epcoritamab (2 step-up doses, then 48-mg full doses per label) in 28-d Cs. The primary endpoint of the expansion cohort was IRC-assessed overall response rate (ORR). A subgroup analysis evaluated efficacy outcomes by investigator assessment in complete responders with longer follow-up. C1 OPT assessed CRS incidence and severity with hydration and dexamethasone prophylaxis in C1; hospitalization was not required. Results: Overall, 157 LBCL pts were treated in the expansion cohort; 148 had diffuse LBCL (DLBCL) or high-grade B-cell lymphoma (HGBCL). Baseline characteristics were previously reported. As of April 21, 2023, the median follow-up for LBCL was 25.1 mo (range, 0.3+ to 32.7); ORR/CR rates were 63/40% (LBCL) and 61/39% (DLBCL + HGBCL) by IRC. In a subgroup analysis of complete responders with longer follow-up (median, 31.3 mo), median duration of CR was not reached; efficacy outcomes for complete responders are shown in the Table. Long-term safety was consistent with previous reports. CRS remained the most common AE (51% all grade [G]; 32% G1, 16% G2, 3% G3). In C1 OPT, 36 pts were evaluable for CRS with a median follow-up of 1.7 mo. Overall CRS incidence was 22% and events were low grade (14% G1, 8% G2), mostly occurring following the first full dose. All CRS events resolved; none led to treatment discontinuation. Among 60 total pts in C1 OPT, 1 pt experienced ICANS (G1). Additionally, IL-6 levels were lower with C1 OPT and consistent with the observed lower rate and severity of CRS. Preliminary C1 OPT efficacy data were comparable to data observed in the expansion cohort. Conclusions: Epcoritamab monotherapy continues to demonstrate deep and durable responses, with most complete responders remaining in CR and without new safety signals in these long-term follow-up analyses. Implementing simple measures of adequate hydration and prophylactic dexamethasone in C1 markedly reduced the overall incidence and severity of CRS with no impact on efficacy. The continued benefit beyond 2.5 y underlines the long-term efficacy and value of epcoritamab in R/R LBCL. Clinical trial information: NCT03625037 . [Table: see text]
Impact of Social Determinants of Health on Predictive Models for Outcomes After Congenital Heart Surgery
Authors: Sarah Crook, Kacie Dragan, Joyce L. Woo, Matthew Neidell, Katherine A. Nash, Pengfei Jiang, Yun Zhang, Chantal M. Sanchez, Stephen Cook, Edward L. Hannan, Jane W. Newburger, Marshall L. Jacobs, Christopher J. Petit, Andrew Goldstone, Robert Vincent, Kathleen Walsh-Spoonhower, Ralph Mosca, T.K. Susheel Kumar, Neil Devejian, Ben Biddix, George M. Alfieris, Michael F. Swartz, David Meyer, Erin A. Paul, John Billings, Brett R. Anderson
Journal: Journal of the American College of Cardiology (2024)
Real world incidence, prevention, and management of tumor lysis syndrome in patients with chronic lymphocytic leukemia treated with venetoclax in the inpatient and outpatient settings.
Authors: Yannis Valtis, David Nemirovsky, Andriy Derkach, Lindsey Elizabeth Roeker, Saumya Sharan, Charlene Kabel, Ricardo Ortiz, Mark Blaine Geyer
Journal: Journal of Clinical Oncology (2024)

7045 Background: Venetoclax (ven) is a BCL2 inhibitor used for the treatment (tx) of chronic lymphocytic leukemia (CLL) which can cause clinical or laboratory (lab) tumor lysis syndrome (TLS). A dose ramp-up schedule and prophylaxis strategies are incorporated into NCCN guidelines and prescribing information. Prior reports have of TLS focused mostly on patients (pts) with relapsed/refractory CLL receiving ven as monotherapy. Methods: We included pts &gt;18y who were diagnosed with CLL or small lymphocytic lymphoma (SLL) and received tx with commercial ven in any line of therapy at our institution from 1/1/2016 to 12/31/2020. TLS was defined using the modified Cairo Bishop Criteria. TLS risk was based on the size of the largest lymph node (LN) on imaging or examination and the absolute lymphocyte count (ALC) as defined by ven prescribing information. Results: We included 616 ven escalations among 136 pts with CLL. Median age was 70 years and 86% were white. Ven was part of first line of tx for 48 pts (35%). 11% had high TLS risk at baseline; 37% among those escalated exclusively inpatient (IP) and 2% among those escalated exclusively outpatient (OP). Among those treated with ven, 47 pts (35%) received ven monotherapy. 74 (54%) of pts were escalated exclusively OP, 35 (26%) had at least one prophylactic hospitalization and 27 (20%) were escalated exclusively IP. During ven initiation, 86% of pts received allopurinol, 71% intravenous hydration, 18% phosphate binders, and 10% prophylactic rasburicase. Among the entire cohort, 8 pts (5.9%) developed lab TLS and zero developed clinical TLS. There were 11 TLS events; 2 pts developed TLS in more than one escalation. Incidence of TLS was 15% for those escalated exclusively IP, 5.7% for those with any prophylactic hospitalization and 2.7% for those escalated exclusively OP. Those who developed TLS were more likely to have a higher TLS risk at baseline, preceding isolated hyperuricemia, or CrCl measurement &lt; 60 mL/min (Table). Conclusions: In this single institution retrospective cohort study, lab TLS was observed, though clinical TLS was not. Baseline hyperuricemia and impaired renal function were more common among those who developed lab TLS compared to those who did not. Prophylactic measures, including use of IV hydration, may have contributed to low rates of observed TLS in the outpatient setting. [Table: see text]
Genomic profiling in a subgroup analysis of patients (pts) with diffuse large B-cell lymphoma (DLBCL) and extranodal (EN) sites of involvement in the phase 3 Pola-R-CHP versus R-CHOP (POLARIX) study.
Authors: Jennifer Kimberly Lue, Franck Morschhauser, Herve Tilly, Georg Lenz, Fabrice Jardin, Alex Francisco Herrera, Jeff Porter Sharman, Christopher Flowers, Jonathan W. Friedberg, Marek Trneny, Charles Herbaux, Mark Yan, Yanwen Jiang, Jamie Hirata, Connie Lee Batlevi, Deniz Sahin, Wilfred Leung, Will Harris, Gilles A. Salles, Laurie Helen Sehn
Journal: Journal of Clinical Oncology (2024)

7061 Background: The prognosis and survival outcomes of pts with EN involvement remain a challenge for DLBCL management. In the Phase 3 POLARIX study (NCT03274492), Pola-R-CHP demonstrated significantly improved progression-free survival (PFS) compared with R-CHOP in previously untreated DLBCL (Tilly et al. 2022). This retrospective analysis assessed clinical outcomes and genomic patterns of pts with DLBCL and EN disease. Methods: POLARIX methods were previously described (Tilly et al. 2022). Using a data cutoff of June 15, 2022, this analysis assessed pts with EN involvement as determined by investigators. Additional outcomes and genomics analyses were performed on pts whose EN status was confirmed from documented radiographic lesions or bone marrow biopsy with denotation of EN disease sites. Hazard ratios (HRs) for investigator-assessed PFS were adjusted for age (≤60 vs &gt;60) and sex. Cell of origin (COO) by NanoString, mutation analysis by whole exome sequencing, and global gene expression profiling by RNAseq were performed centrally. Results: In POLARIX, 616/879 pts (70%) had identified EN involvement. After a median follow-up of 39.7 months, pts showed improved PFS with Pola-R-CHP vs R-CHOP (HR 0.72, 95% confidence interval [CI]: 0.55–0.96), with a 2-year PFS of 75% vs 66%. A total of 556 pts (Pola-R-CHP, n=279; R-CHOP, n=277) had confirmed sites of EN involvement, defined as pts with EN radiographic lesions or bone marrow disease. In these pts, PFS favored Pola-R-CHP vs R-CHOP but the difference was not statistically significant (HR 0.84, 95% CI: 0.63–1.13). Of pts with confirmed EN disease, 429 had COO results (activated B-cell, 145 [34%]; germinal center B-cell, 223 [52%]; unclassified DLBCL, 61 [14%]). Mutation data and frequencies of select clinically relevant mutations (Ptashkin, 2023) across EN sites were available for 364 pts (Table). Gene expression data were available for 418 pts; genes involved in proliferation (E2F or PI3K signaling targets and checkpoint genes) and regulated by IRF4, OCT2 and XBP1, were commonly upregulated in pts with EN disease. Conclusions: Results in pts with DLBCL with EN involvement suggest superior PFS with Pola-R-CHP vs R-CHOP. Ongoing analyses will further assess the independent impact of EN status on outcome. POLARIX represents the largest cohort of pts with annotated EN disease and systematic genomic analysis, providing new insights into the genomics of these pts. Clinical trial information: NCT03274492 . [Table: see text]