tbuckley/cabot-search huggingface dataset:
CELESTIAL-TNCLL: An ongoing, open-label, multiregional, phase 3 study of sonrotoclax (BGB-11417) + zanubrutinib vs venetoclax + obinutuzumab for treatment-naïve (TN) CLL.
Authors: Mazyar Shadman, Arnon P. Kater, Jennifer Ann Woyach, Jianyong Li, Talha Munir, Tommi Salmi, Patrick Phuong, Tian Tian, Piers Patten
Journal: Journal of Clinical Oncology (2024)

TPS7087 Background: The combination of venetoclax (ven), the first-generation BCL2 inhibitor, and ibrutinib, a BTK inhibitor, has demonstrated efficacy in patients with CLL (Wierda et al. J Clin Oncol. 2021); however, the toxicity profile of this regimen suggests a need for a more tolerable BTK/BCL2 inhibitor combination. Sonrotoclax, a next generation BCL2 inhibitor, is a more selective and more pharmacologically potent inhibitor of BCL2 than venetoclax. In a phase 1 study in patients with TN CLL treated with sonrotoclax + zanubrutinib, efficacy data was promising with ORR and 1-year progression-free survival (PFS) rates of 100% and deep responses based on undetectable measurable residual disease at &lt;10 -4 sensitivity (uMRD4). The most common grade ≥3 TEAE was neutropenia, and no tumor lysis syndrome or cardiac toxicity was observed (Tam et al. Blood. 2023). Zanubrutinib, a next-generation BTK inhibitor, significantly improved PFS and had a more tolerable safety profile, including fewer cardiac adverse events vs ibrutinib in a randomized, head-to-head study of patients with CLL/SLL (Brown et al. N Engl J Med. 2023). Presented here is the design of a phase 3 trial aimed at comparing the efficacy of sonrotoclax + zanubrutinib vs ven + obinutuzumab (obi) in patients with TN CLL. Methods: CELESTIAL-TNCLL (BGB-11417-301; NCT06073821) is a randomized, open-label, phase 3 study. Eligible patients must have previously untreated CLL that requires treatment per 2018 iwCLL criteria, measurable disease by CT/MRI, an ECOG performance score of 0-2, and adequate hematologic and organ function. Approximately 640 patients will be randomized 1:1 to receive either 3 cycles of zanubrutinib monotherapy (320 mg total daily dose, orally), followed by zanubrutinib + sonrotoclax for 12 cycles, or standard ven + obi treatment for 12 cycles. Randomization will be stratified by age (&lt;65 vs ≥65 years) and IGHV and del(17p)/ TP53 mutation status. The primary endpoint is PFS as assessed by independent review committee (IRC) according to 2018 iwCLL guidelines with modifications for treatment-related lymphocytosis for patients with CLL (Cheson et al. 2012). Key secondary endpoints include complete response rate (CRR), defined as CR or CR with incomplete hematopoietic recovery, assessed by IRC; rates of uMRD4 in bone marrow and peripheral blood at the first post-treatment follow-up visit based on next-generation sequencing by clonoSEQ; and overall survival. Other secondary endpoints include PFS as assessed by investigator (INV); CRR by INV; rate of uMRD4 based on flow cytometry; overall response rate by IRC and INV; duration of response by IRC and INV; patient-reported outcomes; and safety and tolerability. Recruitment is ongoing. Clinical trial information: NCT06073821 .
First-line treatment of follicular lymphoma (FL) with golcadamide, rituximab +/- nivolumab: An umbrella randomised phase 2 investigator-led study.
Authors: Geoffrey Chong, Jodie Palmer, Allison Barraclough, Leonid Churilov, Colm Keane, Sze Ting Lee, Denise Lee, Sumita Ratnasingam, Charmaine Smith, Eliza Anne Hawkes
Journal: Journal of Clinical Oncology (2024)

TPS7092 Background: The most common therapy FL pts receive remains chemotherapy which yields high efficacy but also significant toxicity.(Marcus 2017, Rummel 2013). FL pts are largely aged over 65 and may require treatment multiple times over their disease course thus novel regimens which enhance efficacy and minimise toxicity are highly desirable. FL patient (pt) outcomes are influenced by tumor microenvironment composition and manipulation with immunotherapy. Ikaros and Aiolos, key cell development and homeostasis transcription factors are upregulated in FL. Cereblon-modulating compounds (CELMoDs) such as golcadomide (G) promote degradation of these with demonstrated efficacy alone or with rituximab (R) in FL (responses-ORR- upto 75% in heavily pre-treated FL pts) (Morschhauser 2018, Michot 2021). We reported favourable efficacy of nivolumab (N) a PD1 inhibitor plus R in 1L treatment of FL (ORR 92% complete response CR 54%). (Hawkes 2021).This study (‘TOP-FLOR’; NCT05788081) builds on these findings and potential immunomodulatory synergy to explore the efficacy and safety of R + G, a novel CELMoD +/- N in treatment-naïve advanced stage FL pts. Methods: This is an open label multicentre umbrella Bayesian Optimal randomised Phase 2 trial (n=40). Eligibility includes: age &gt;18 years, treatment-naïve, stage II-IV, low grade FL, ECOG 0-2. Pts from 5 Australian sites are randomised 1:1 to receive 8 cycles of R-G +/-N 8 cycles of 28 days (D) each as follows: Arm A; R 375 mg/m2 IV D1 + G 0.4 mg orally D1- 14; Arm B; R-G as above +N 480mg IV D1. All pts in partial response (PR) or CR post cycle 8 receive 8 doses of 12-weekly R maintenance. The primary endpoint (EP) is CR rate post induction in the absence of prohibitive toxicity (CTCAE V5.0). Secondary EP are overall toxicity, ORR (as per Lugano criteria), time to treatment failure, progression free survival, overall survival. Exploratory EP include: pt reported outcomes, PET radiomics, laboratory biomarkers. Study assessments include safety assessments every cycle until D28 post final study drug delivery. Response assessments (PET/CT), pt reported outcomes &amp; biomarker bloods are performed at baseline, post cycles 2, 5 &amp; 8, then 6 monthly during R maintenance. Futility analysis occurs after 11 pts are recruited to each arm with &lt; 7 pts achieve the primary EP. Treatment arms will not be formally compared. Kaplan-Meier analysis will be used to report survival probabilities. This trial received IRB approval on 14 July 2023 (HREC/88597/Austin-2023). To date 15 pts have been randomised. Clinical trial information: NCT05788081 .
Access to palliative care in patients with multiple myeloma in the USA: A National Cancer Database (NCDB) analysis of years 2004-2020.
Authors: Ludovic Saba, Chieh Lin Fu, Kaylee Sarna, Chakra Pani Chaulagain
Journal: Journal of Clinical Oncology (2024)

7563 Background: Palliative care (PC) can improve the quality of life for patients with multiple myeloma (MM). Despite its recognized importance, research gaps persist in understanding factors influencing PC accessibility and utilization, particularly in the diverse MM patient landscape in the real-world setting. This study explores potential associations between race, ethnicity, socioeconomic factors, and PC access for MM patients in the USA. Methods: Utilizing the NCDB, we identified 202,949 MM patients diagnosed from 2004 to 2020. Multivariate logistic regression analysis was conducted with SAS version 9.4, to determine independent factors predicting PC access. Results: Analysis of 202,949 MM patients revealed notable disparities for access to PC. Female patients exhibited lower PC odds (OR: 0.94, p &lt; 0.0001) compared to male patients, as did Black patients (OR: 0.80, p &lt; 0.0001) and other racial groups (OR: 0.84, p &lt; 0.0001) compared to White patients. Hispanic ethnicity was associated with lower PC utilization odds (OR: 0.84, p &lt; 0.0001) compared to non-Hispanics. Earlier years (2004-2007) showed higher PC odds (OR: 1.12, p &lt; 0.0001), while subsequent years (2008-2011, 2012-2015) exhibited lower odds (OR: 0.93, p = 0.0009; OR: 0.87, p &lt; 0.0001, respectively) compared to the most recent years (2016-2020). Academic settings had lower PC odds than non-academic facilities (OR: 0.78, p &lt; 0.0001). Insurance status varied, with no insurance (OR: 1.40, p &lt; 0.0001), Medicaid (OR: 1.17, p &lt; 0.0001), and other government insurance (OR: 1.38, p &lt; 0.0001) linked to higher PC odds compared to private insurance. Lower annual household incomes (&lt;$38,000, $38,000-$47,999, $48,000-$62,999) had increased PC odds compared to higher incomes (&gt;$63,000) (all p &lt; 0.0001). Areas with a higher percentage of individuals without a high school degree exhibited lower PC odds, notably 21% (OR: 0.83, p &lt; 0.0001) and 13.0%-20.9% (OR: 0.94, p = 0.0222) compared to &lt;7.0% without a high school degree. Greater distance (&gt;30 miles) reduced PC odds compared to shorter distance (&lt;10 miles) to treatment facility (OR: 0.83, p &lt; 0.0001). A Charlson-Deyo score of 1 increased PC odds compared to a score of 0 (OR: 1.12, p &lt; 0.0001). Conclusions: Our real-world analysis reveals substantial disparities in MM patients’ PC access and utilization. Female patients and minority groups (Blacks and Hispanics) face significant challenges. The dynamic trends over time and socioeconomic impacts underscore the need for integrating PC and targeted interventions for overall MM patient well-being. Our findings pave grounds for future prospective studies.
Multiple myeloma in the African American population: A 2010-2020 NCDB analysis.
Authors: Niraj Neupane, Harkarandeep Singh, Pravash Budhathoki, Utsav Joshi, Asis Shrestha, Shreeja Shikhrakar, Aakriti Parajuli, Apurwa Prasad, Binod Dhakal
Journal: Journal of Clinical Oncology (2024)

e19531 Background: Multiple myeloma (MM) exhibits a disproportionately higher prevalence among African American individuals. Various factors contribute to the disease's progression, severity, and prognosis. This analysis presents real-world data from the National Cancer Database (NCDB) from 2010 to 2020. Methods: Cohort of 241,446 MM patients between 2010 and 2020 were analyzed. Demographic variations, including age, gender, insurance status, educational attainment, and median household income, were examined. Multivariate Cox regression analysis was conducted to identify factors influencing survival outcomes. Results: Within the database, from 2010 to 2020, 51,668 cases of multiple myeloma were recorded among Black individuals. The age group most affected was 40 to 65 years (50.2%), followed by those over 65 (47.3%), with 2.5% falling between 18 to 40 years, and a mean age of 64.4 years. Most cases affected females (51.5%), with most households earning less than $40,227 annually. A significant portion of Black patients did not receive a transplant (83.8%) or immune based option (73.1%). The mean duration from diagnosis to therapy initiation was 37.5 days. Multivariate analysis revealed that patients over 65 had a worse prognosis (HR = 1.52, 95% CI: 1.47 – 1.57, P &lt; 0.001) compared to those under 65, while females exhibited a better prognosis (HR = 0.88, 95% CI: 0.86 – 0.91, P &lt; 0.001). Patients with private insurance had better outcomes (HR = 0.73, 95% CI: 0.68 – 0.78, P &lt; 0.001), as did those treated in academic centers (HR = 0.89, 95% CI: 0.87 – 0.92, P &lt; 0.001). Additionally, patients receiving any form of transplant had better outcomes (HR = 0.45, 95% CI: 0.42 - 0.49, P &lt; 0.001), along with those undergoing chemotherapy (HR = 0.73, 95% CI: 0.68 – 0.78, P &lt; 0.001) and immunotherapy (HR = 0.67, 95% CI: 0.64 – 0.69, P &lt; 0.001). Conclusions: The analysis highlights significant demographic and treatment influences among African American patients with MM. Some identifiable factors associated with improved outcomes include younger age, female gender, private insurance, treatment in academic centers, and most importantly receipt of transplant and Immunotherapy. These findings underscore the importance of targeted interventions considering various factors and improving outcomes in this population. [Table: see text]
Immunohistochemical markers in the prognostic model for survival of patients with diffuse large B-cell lymphoma.
Authors: Odiljon Kobilov, Sergey Kamishov
Journal: Journal of Clinical Oncology (2024)

e19055 Background: Currently, relevant issues include the study of the role of immunohistochemical markers in patients with diffuse large B-cell lymphoma (DLBCL) with extranodal involvement to predict the outcomes of the conducted therapy. Methods: A retrospective study included 81 patients with diffuse large B-cell lymphoma (DLBCL) involving the liver and spleen with extranodal manifestations, who underwent treatment and were under outpatient monitoring in a hospital setting. The average age of the patients was 60.7±7.5 years. The expression of pan-B-cell antigens CD20, CD79A, PAX 5 (monomorphic intense nuclear expression), CD5, CD45, CD30, BCL-2, BCL-6, Ki-67, MUM1, GCET1, FOXP1 was examined in the patients. To exclude the polymorphic blastoid variant of lymphoma with CD5 expression in mantle cells, the study of cyclin D1 expression was conducted. Results: All patients began treatment with R-CHOP chemotherapy. In 37 cases, this regimen had to be replaced with DHAP in 23 (62.2%) patients due to the low effectiveness of the 1st-line chemotherapy, and in 14 (37.8%) after completing the full course (6 cycles) of treatment. Over the 6-year observation period, despite identical treatment, the 5-year survival rate was 60.5%. Among 32 (39.5%) patients, there was a fatal outcome due to the progression of the pathological process during treatment. Moderate expression was characteristic for the markers CD5, CD30, PAX-5, FOXP1, and GCET1, while high expression was observed for CD10, CD45, CD79A, Bcl-6, MUM1, and Ki-67. High expression of Bcl-2, Bcl-6, GCET1, and Ki-67 exceeding 60% is a prognostically unfavorable factor significantly impacting the survival of patients. The most unfavorable outcomes were observed with the combination of Bcl-2 and Ki-67 expression exceeding 60% along with CD-45. The combination of Ki-67 expression exceeding 60%, CD-79, and MUM1 also resulted in an unfavorable outcome in all cases. The prognostic scale, using Cox's proportional hazard, allows predicting the prognosis of diffuse large B-cell lymphoma with extranodal involvement with a probability of 87.2%. Conclusions: In our studies, it has been demonstrated that adverse immunohistochemical characteristics of diffuse large B-cell lymphoma with extranodal involvement include high expression of Bcl-2, Bcl-6, GCET1, and a Ki-67 proliferation index exceeding 60% (p&lt;0.025).
Outcome of patients with primary CNS lymphoma treated with methotrexate based regimens: A retrospective study.
Authors: Yeshanew Teklie, Zaw Win Myint, Raghuveer Ranganathan, Darin Poei, Graham Blake Parker, Shirley Ye
Journal: Journal of Clinical Oncology (2024)

e19051 Background: Primary central Nervous system Lymphoma is an aggressive Non-Hodgkins Lymphoma with 5-year survival of only 30 percent. Few studies have addressed the comparison of induction treatment regimens with various risk stratification groups with no consensus on the optimal methotrexate dose for best complete overall response and survival outcome. Our retrospective study compares induction treatment regimens, identifies different risk stratification factors, and provides insight into the best induction treatment regimen with determination of optimal methotrexate dose. Methods: Design: Retrospective Primary Outcomes: Complete response rate, overall survival rate with risk stratification based on histology, Ki-67, and initial albumin level. Results: 77 patients 18 years of age and older with PCNSL at NCC and LAC between June 2015 and July 2022 were included in the study. Overall, 50% of patients were treated with CALGB50202 induction regimen,19% with R-MPV,12 % with De-Angelis regimen. CALGB 50202 has the highest survival rate of 63.4% followed by R-MPV with 22% survival rate followed by De-Angelis regimen with 0% survival rate with chi-square test P-value &lt; 0.001 during the study period. Similarly, CALGB 50202 has the highest CR rate of 61.9% followed by R-MPV with CR rate of 16% followed by De-Angelis regimen with the lowest CR rate of 2.4%.CR rate comparison is statistically significant with P-value of &lt; 0.0001. The study assessed optimum methotrexate dose. The mean and median total methotrexate dose in patients who were alive during the study period was 74.3 grams and 81.7 grams respectively as compared to mean value of 34.2 grams and median of 19.3 grams in patients who died with a p-value of 0.0019.Comparing survival based on histology as germinal center versus non-germinal center PCNSL, the later has higher mortality rate of 64.7 % as compared to 11.8 % in patient with germinal center PCNSL.Ki-67 was assessed as &gt;80% and &lt;80%.Among patients who were alive during the study period,48.8% have Ki-67 &gt; 80% as compared to only 12.2%.On the other hand, among the patients who died,47.1% of patients have Ki-67 &lt;80%,indicating lower ki-67 associated a lower survival outcome as depicted on the Kaplan Meier curve with P-value of 0.004. Patients with normal initial albumin have a higher chance of survival (78%) vs 22% in the group with low albumin level with p-value of 0.0005. Conclusions: CALGB 50202 had the highest CR and survival rates followed by R-MPV regimen in patients with primary CNS lymphoma. The total dose of methotrexate patient receives was an important factor for survival and CR and the optimal total methotrexate dose was 70-80 grams. Normal initial albumin, high Ki-67, and germinal center histology favored better survival.
Patient-reported outcomes (PROs) from the DREAMM-7 randomized phase 3 study comparing belantamab mafodotin, bortezomib, and dexamethasone (BVd) vs daratumumab, bortezomib, and dexamethasone (DVd) in patients with relapsed/refractory multiple myeloma (RRMM).
Authors: Vania Hungria, Pawel Robak, Marek Hus, Chengcheng Fu, Vera Zherebtsova, Christopher Ward, Ana Carolina de Almeida, P. Joy Ho, Roman Hajek, Claudio Cerchione, Nicholas Pirooz, Astrid McKeown, Hena Baig, Lydia Eccersley, Farrah Pompilus, Simon McNamara, Chee Paul Lin, Sumita Roy-Ghanta, Joanna Opalinska, Maria-Victoria Mateos
Journal: Journal of Clinical Oncology (2024)

7543 Background: Belantamab mafodotin(belamaf), a first-in-class antibody-drug conjugate targeting B-cell maturation antigen, acts through a multimodal mechanism including direct cell killing and immune-mediated mechanisms. The global, phase 3, open-label, randomized, DREAMM-7 trial (NCT04246047) met its primary endpoint of demonstrating statistically significant progression-free survival benefit favoring BVd vs DVd in patients with RRMM who had received ≥1 prior line of therapy; here, we report PRO findings for BVd vs DVd. Methods: Patients were randomized (1:1) to receive BVd or DVd and completed electronic PRO measures at baseline and every 3 weeks (Q3W) during treatment. PRO measures included EORTC-QLQ-C30, EORTC-QLQ-MY20 disease symptoms (pain), PRO-CTCAE patient-reported tolerability, and OSDI vision-related functioning (Q3W up to the sixth dose of belamaf, then Q6W). Each domain was summarized using descriptive statistics. Results: Among 494 patients (BVd, n=243; DVd, n=251), adherence to PRO assessments was &gt;90% for most study visits. There was no difference in EORTC QLQ-C30 global health status/quality-of-life assessments between the study arms over time. Similarly, role functioning, physical functioning, fatigue, and pain were stable (change from baseline in EORTC score was within 10 points) over time and consistent between arms. Most symptomatic adverse events evaluated by PRO-CTCAE were reported at no to low severity, frequency, and interference (PRO-CTCAE ratings ≤2) in both arms throughout the study. The severity and interference of blurred vision and frequency of watery eyes were reported at higher levels (PRO-CTCAE ratings ≥3) in the BVd arm. Among patients in the BVd arm with a clinically meaningful deterioration in vision-related functioning (a change from baseline of ≥12.5 points), EORTC-QLQ-C30 global health status, role functioning, and physical functioning were comparable to the DVd arm over time. Conclusions: Overallquality of life, role functioning, physical functioning, fatigue, and pain were comparable in patients treated with BVd vs DVd. In patients treated with BVd who reported a clinically meaningful deterioration in vision-related functioning, overall quality of life was consistent with the DVd arm.
Demographic and survival data of patients with primary diffuse large B-cell lymphoma of the head and neck: A single center experience.
Authors: Mehmet Mutlu Kidi, Sedat Biter, Yasemin Aydinalp Camadan, Sendag Yaslikaya, Tolga Koseci, Ertugrul Bayram, Umut Disel, Berksoy Sahin, Ismail Oguz Kara
Journal: Journal of Clinical Oncology (2024)

e19069 Background: Head and neck malignancies account for around 10% of lymphomas, with diffuse large B-cell lymphoma (DLBCL) being the most prevalent histologic subtype. Head and neck lymphoma is as the second most pervasive location for extra-nodal lymphoma, following the gastrointestinal system. This study focused on examining the demographic characteristics, main localization distribution, and survival rate of patients with head and neck lymphoma at the Çukurova University Medical Oncology Clinic. Methods: We conducted a retrospective analysis of 97 individuals diagnosed with single-center, head, and neck diffuse large B-cell lymphoma (DLBCL) from 2011 to 2020. Data pertaining to patients was acquired from electronic medical records. The patients were categorized based on anatomical localization, and survival rates and survival data were computed for each primary localization. Results: Out of the total number of patients, 48 (49.5%) were female, and 49 (50.5%) were male. The patients had a median age of 59.5 years. Waldeyer's ring was the most frequent site of primary head and neck tumor localization in patients with DLBCL, accounting for 42.4% of cases. The distribution of anatomical sites was as follows: nasopharynx accounted for 30.8%, nasal cavity accounted for 10.3%, thyroid accounted for 6.2%, parotid accounted for 5.2%, oral cavity accounted for 3.9%, and other anatomical sites accounted for 1.2%. Based on the Ann Arbor staging approach, 65% of the patients were classified as stage I-II. The 3-year survival rate was 71%, while the 5-year survival rate was 61%. The overall survival of individuals with nasopharyngeal lymphoma was considerably shorter when compared to those with non-nasopharyngeal lymphomas (p=0.0372). Conclusions: We conducted a thorough analysis of the data pertaining to lymphomas characterized by diffuse large B-cell lymphoma (DLBCL) occurring in the head and neck region. The study found that when the nasopharynx is affected, it is linked to a worse prognosis and may necessitate more intensive treatment. Our work is a retrospective study conducted at a single center. However, future investigations with a more significant number of participants and a prospective design is necessary.