bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of AVM0703 treatment on the limitations of R-CHOP and survival in a model applicable to ABC subtype DLBCL.
Authors: Deisher Theresa , Mittal Sandeep , Sawas Spencer , Michiels McKenzie , Jarzyna Peter 
Published: June 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 2x106 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 mm3. 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 >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]
Demographic and survival data of patients with primary diffuse large B-cell lymphoma of the head and neck: A single center experience.
Authors: Kidi Mehmet Mutlu , Biter Sedat , Aydinalp Camadan Yasemin , Yaslikaya Sendag , Koseci Tolga , Bayram Ertugrul , Disel Umut , Sahin Berksoy , Kara Ismail Oguz 
Published: June 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.
An institutional experience of a rare diagnosis of subcutaneous panniculitis-like T-cell lymphoma.
Authors: Fort Callie , Raina Rohit , Surapaneni Rakesh 
Published: June 2024

e19073 Background: Subcutaneous Panniculitis-like T-cell lymphoma (SPTCL) is a rare diagnosis making up < 1% of Non-Hodgkin lymphomas. Data from Surveillance Epidemiology and End Results (SEER) identified a total of 204 cases from 2000-2020. Clinically, SPTCL presents as subcutaneous nodules and is difficult to distinguish from other more common conditions such as lupus erythematosus panniculitis. Most of our understanding on presentation, diagnosis and treatment on SPTCL is limited to small case series. Methods: Following IRB approval, a multi-center retrospective clinical and pathological review identified patients diagnosed with SPTCL from 1/1/2013-10/24/23. The study was conducted at Baylor Scott & White system (CTX). Inclusion criteria included ≥ 18 years old, SPTCL AB sub-type. Patients were seen for > 2 visits during time of active treatment. Cases of SPTCL y8 sub-type were excluded from the study. A descriptive analysis of the clinical presentation, treatment choice/duration, and clinical outcomes was generated. Results: A total of 5 patients met criteria for inclusion during the previously defined time period. The median age at diagnosis was 39 with a median follow up of 6 years. Patients presented with multiple nodular lesions affecting the chest, trunk, axilla, arms, and legs. Sixty percent of patients received misdiagnosis and experienced delay in appropriate treatment with a maximum delay of 10 years. Histopathology showed panniculitis-like lymphoid infiltrate composed predominantly of T lymphocytes, with areas of adipocyte rimming and a background of fat necrosis. No patients developed hemophagocytic syndrome. Patients were treated with steroids alone or in combination with cyclosporine, methotrexate, and/or romdespin. Sixty percent of patients achieved a complete response, and 40% remain in remission. The 5-year disease specific survival rate was 100%. Conclusions: SPTCL showed an indolent course in the patient population studied. All patients treated with systemic steroids as first line therapy responded favorably. When tolerated cyclosporine and methotrexate controlled disease in patients that showed progression following the completion of steroid taper.
Outcomes of ide-cel in patients with relapsed/refractory multiple myeloma: A single-institution experience.
Authors: Trando Aaron , Ghamsari Farid , Yeung Philip , Costello Caitlin , Saunders Ila M. , Jeong Ah-Reum 
Published: June 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.
Analysis of real-world (RW) pomalidomide (pom) dosing patterns in patients (pts) with multiple myeloma (MM) from the Flatiron database.
Authors: Dhakal Binod , Godara Amandeep , Medvedova Eva , Naik Seema , Nooka Ajay K. , Parekh Trilok V. , Hadley David , Kansagra Ankit J. , Anderson, Jr Larry D. 
Published: June 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 >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 <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]
Survival shifts in multiple myeloma: Evaluating the impact of therapeutic advances and racial disparities after a decade of change.
Authors: Hebishy Ahmed , Zweigle Joshua Walter , Hussain Ali , Muzaffar Mahvish 
Published: June 2024

e19509 Background: Multiple myeloma (MM) is the second most common hematologic malignancy and is considered an incurable disease. However, the last two decades have witnessed the emergence of new therapies that have improved overall survival by several folds. In the current study, we are examining the evolving trends in age-adjusted incidence and relative survival among myeloma patients over the last 20 years, specifically focusing on discerning disparities in these trends based on racial classifications. Methods: We performed a retrospective cohort study using the SEER Plus Data, 12 registries, Nov 2022 Sub (1992-2020) to calculate the age-adjusted incidence and relative survival rate (RSR) of MM in the US in two specific time intervals 2001-2010 & 2011-2020 consistent with changes in MM treatment during 2011-2020 including the emergence of immunomodulatory drugs (IMiDs). The year of diagnosis, sex, and race data were available for each case. We excluded cases diagnosed before 2001 and after 2020. Patients were stratified by sex and categorized into two racial groups: White and Black. The 60-month (5-year) and 116-month (used as a 10-year estimate) RSR and age-adjusted incidence rate were calculated for the cohort and each racial group. We calculated survival utilizing the Kaplan-Meier method. Using the log-rank test, we also found hazard ratios (HR), with the corresponding CI for each racial group stratified by sex. Results: We investigated MM incidence and survival rate trends over two decades while considering gender and race. The age-adjusted incidence rate showed a significant overall increase from 6.5 to 7.4 per 100,000, with changes in gender-specific rates. Higher incidence rates among Black populations were noted. Cohort relative survival analysis revealed improved median survival (53 to 83 months) and increased relative survival rate both at five years (46.4% to 56.3%) and at ten years (28.8% to 40.8%). An investigation based on race revealed substantial improvements among both White and Black populations. The HR (Table) emphasized the improved survival outcomes for patients diagnosed in period two across genders and races. Conclusions: The study highlights the changes in the incidence and survival rates of MM. Notably, MM incidence has seen a significant rise in the last decade, particularly among the Black population. The survival of patients diagnosed between 2011 and 2020 revealed statistically significant improvement at both the 5- and 10-year mark compared to patients diagnosed between 2001 and 2010. [Table: see text]
Incidence of thromboses and secondary cancers in patients with multiple myeloma after lenalidomide-based induction followed by maintenance as first-line therapy: A systematic review and meta-analysis.
Authors: Mahadevia Himil , Gaur Rishabh , Shaddarsanam Phanisri , Gutta Neha , Wang Xi , Cheng An-Lin , Shrestha Anuj 
Published: June 2024

e19510 Background: Lenalidomide, an immunomodulatory drug (IMiD) is one of the backbones of standard first-line induction regimen for multiple myeloma (MM). Lenalidomide maintenance is associated with improved progression-free survival, especially after bone marrow transplantation. The optimal duration of maintenance therapy is unknown. In our study, we evaluated the incidence of any thrombosis, venous thrombosis (VTh) and arterial thrombosis (ATh) as well as any secondary cancers, secondary solid and hematologic cancers in patients with MM who received lenalidomide-based first-line induction followed by lenalidomide maintenance for at least 6 months. Methods: This systematic review identified pertinent clinical trials from MEDLINE, Embase, and CENTRAL databases from inception to December 31, 2023. After two rounds of review by 4 authors independently, 25 clinical trials in patients with MM met the above eligibility criteria. The number of cases with any thrombosis, VTh, ATh, any secondary cancers, secondary solid and hematologic cancers along with the total number of patients in the arms with lenalidomide-based therapy were extracted from each trial. The incidence meta-analysis was performed using the “meta” package version 6.2-0 of R version 4.2.2 via a random-effects model. Pooled incidence and its associated 95% confidence interval (CI) were reported for each outcome. I² statistic was used to determine the heterogeneity of the studies. Results: 10743 patients were reviewed from 25 clinical trials. The pooled incidence rate of any thrombosis was 4% (0.04; 95% CI: 0.03 to 0.06, I2=91%). The pooled incidence rate of arterial thrombosis and venous thrombosis was 1% (0.01; 95% CI: 0.00 to 0.02, I2=77%) and 4% (0.04; 95% CI: 0.02-0.09, I2=94%) respectively. The pooled incidence rate of any secondary cancer was 5% (0.05; 95% CI, 0.04 to 0.07, I2=93%). The pooled incidence rate of secondary hematological malignancies was 2% (0.02; 95% CI, 0.01 to 0.03, I2=90%) and secondary solid cancers was 4% (0.04; 95% CI, 0.03 to 0.06, I2=76%). Conclusions: IMiDs are one of the backbones of the MM regimen. Our meta-analysis showed lenalidomide-based regimen increased the risk for thromboses – higher for VTh (4%) and slightly higher for ATh (1%). It also showed a higher rate of secondary cancers – both solid (4%) and hematologic cancers (2%). However, our study showed considerable heterogeneity. These events become clinically important as patients with MM live longer. MM patients on lenalidomide maintenance could benefit from an active surveillance, monitoring and early treatment program for these long-term adverse effects. VTh prophylaxis based on the type of regimen is already standard. Secondary cancer surveillance may need to be individualized for MM patients in remission.
Association of posterior reversible encephalopathy syndrome with proteasome inhibitors approved for multiple myeloma: Analysis of FAERS database.
Authors: Singh Harkarandeep , Kaur Uttamjot , Neupane Niraj , Kharel Himal , Saeed Hassan , Gill Prabhsimrat , Shrestha Asis 
Published: June 2024

e19515 Background: Proteasome inhibitors (PI) are a class of drugs that are used in the treatment of Multiple Myeloma. There are currently three PIs (Bortezomib, Carfilzomib, and Ixazomib) approved by FDA for this indication. Peripheral neuropathy has been described as one of their most common side effects but the association with another life-threatening neurological disorder, Posterior Reversible Encephalopathy Syndrome (PRES), remains poorly understood. Methods: We conducted a retrospective pharmacovigilance study using the FDA Adverse Event Reporting System database to analyze the risk of PRES associated with various Proteasome Inhibitors. We employed disproportionality signal analysis and calculated the reporting odds ratio with a 95% confidence interval. Results: A total of 79,450 adverse events were found within the FAERS database that were associated with the three FDA approved PIs. PRES accounted for 274 cases, of which 165 cases were in females and 71 cases in males. Majority of patients were adults, with 119 cases between 18-64 years of age, 88 cases above 65 years, and 50 cases with age not specified. Death was reported in 70 cases while 74 cases were marked as having life threatening illness, and 152 cases needed hospitalization. Bortezomib accounted for most cases (202 cases, ROR 6.03, 95% CI 5.3-7.1), followed by Carfilzomib (68 cases, ROR 7.2, 95% CI 5.7-9.1), and Ixazomib (9 cases, ROR 0.99, 95% CI 0.5-1.7). Conclusions: The study helps to shed light on the incidence, and hospital outcomes of PRES associated with various proteasome inhibitors. Significant safety signals were found for Bortezomib, and Carfilzomib. Females were almost 2.5 times more likely to develop PRES compared to males. These findings highlight the importance of keeping a high index of suspicion for PRES while evaluating patients on PIs who present with concerning neurological symptoms.