bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence and outcomes of immune-related adverse events after immune checkpoint inhibitors in patients with Hodgkin lymphoma.
Authors: Lin Cindy (Hsin-Ti) , Tse William W. , Wang Jiasheng
Published: June 2023

e19513

Background: Immune checkpoint inhibitors (ICIs) have recently been found to be effective in Hodgkin lymphoma (HL). However, given the impaired systemic immune response in HL, it is unclear whether immune-related adverse events (irAEs) would manifest differently in this population; data on this topic remains scarce. Methods: Data were collected from an aggregated electronic medical record (EMR) database TriNetX Research Network (TriNetX LLC., Cambridge, Massachusetts, USA). Adult patients diagnosed with HL who received pembrolizumab or nivolumab between 1/2018 and 1/2022 were included. irAEs were identified through a set of validated ICD-10-CM codes. Results: Within the study period, a total of 567 patients with HL were identified. Among them, 363 (63.8%) patients received nivolumab and 263 (46.4%) received pembrolizumab. The mean age was 50.1 (SD 19.6) years-old, 227 (40.0%) patients were female, 69 (12.2%) were black, and 156 (27.5%) received ICI-based therapy as the frontline treatment. irAE of any grade occurred in 280 (49.4%) of patients. Patients who experienced irAEs were more likely to be older (p = 0.0106), while using ICIs as the frontline or after various previous treatments was not associated with irAEs (Table). Among specific irAEs, skin toxicities, thyroid dysfunction, pneumonitis, colitis, and hepatitis occurred in 31.6%, 23.6%, 2.8%, 9.3%, and 3.2% of patients, respectively. Regarding the management for irAEs, systemic steroids, topical steroids, mycophenolate, and infliximab were used in 63.6%, 36.8%, 3.6%, and 3.6% of patients, respectively. Of note, ICIs were able to be resumed in 71.1% of patients with irAEs. After propensity-score matching for known prognostic factors for HL, patients with or without irAE had similar overall survival (OS) (hazard ratio 0.84, 95% confidence interval 0.57 to 1.23, p=0.36). No significant difference of OS was seen across different subtypes of irAE, including skin toxicities (p=0.64), thyroid dysfunction (p=0.74), or colitis (p=0.28). Conclusions: irAEs were common in patients with HL receiving ICIs. The majority of patients with irAEs were able to resume ICIs, and the development of irAEs did not affect overall survival. [Table: see text]
Hodgkin lymphoma mortality trends in age subgroups from 1999 to 2020 in the United States.
Authors: Varughese Tony , Koprivnikar Jamie
Published: June 2023

e19515

Background: Hodgkin Lymphoma has a bimodal distribution with the first peak between ages 15-35 and the second peak being 55 years old and older. Advancements in treatment therapies have improved mortality such that Hodgkin Lymphoma is considered a curable disease. However, treatment outcomes in elderly patients are inferior to those of younger patients. In our study, we analyzed Hodgkin Lymphoma mortality from 1999 to 2020 in the United States. We investigated age-adjusted mortality rates and annual percent changes with a sub-group analysis. Methods: Using the CDC Wonder database, we examined mortality trends from 1999 to 2020 for Hodgkin Lymphoma in adults age 55 and older in the United States. Age-adjusted mortality rates (AAMRs) were calculated per 100,000 people and stratified patients by sex, race/ethnicity, and census region. We computed the annual percentage change trends for the respective stratification using Joinpoint regression software. Additionally, a comparison group between ages 15 and 54 was added for the analysis. Results: In the United States, between 1999 and 2020 there were 24,898 deaths from Hodgkin Lymphoma in Adults 55 and older. The overall age adjusted mortality rate improved from 1.9 per 100,000 people to 1.4, with a respective APC of -2.06%. Our subgroup analysis by sex, race, and census region showed improvements circumferentially. Males consistently had higher rates of improvement than females. Most notably black patients had the lowest difference in AAMR from 1999 to 2020 (0.2), however, white patients and Hispanic patients respectively had higher AAMRs. The comparison group ages 15-54 had lower AAMR change from 1999 to 2020 by sex, race, and region. However, the respective AAMR for the age 15-54 group was significantly lower. Conclusions: Hodgkin Lymphoma has had significant age adjusted mortality rate improvements since 1999. Comparing adults 55 and older to patients 15-54 there is still a notable difference in AAMR. The greater magnitude of improvement in AAMR in older adults with Hodgkin Lymphoma may be related to the approval of agents such as brentuximab vedotin, which has improved tolerability as compared to bleomycin. Alleviating pulmonary toxicity with this novel agent may be more relevant in an older patient population with increased comorbidities. Further, research is needed to continue to identify more efficacious and less toxic therapies for older individuals with Hodgkin Lymphoma. [Table: see text]
Five-year subgroup analysis of tafasitamab + lenalidomide from the phase II L-MIND study in patients with relapsed or refractory diffuse large B-cell lymphoma.
Authors: Duell Johannes , Abrisqueta Pau , Dreyling Martin H. , Gaidano Gianluca , González Barca Eva , Jurczak Wojciech , Maddocks Kami J. , Menne Tobias , Tournilhac Olivier , Bakuli Abhishek , Amin Aasim , Gurbanov Konstantin , Salles Gilles A. , Nagy Zsolt
Published: June 2023

e19522

Background: The Phase II L-MIND study led to accelerated US approval and EU conditional authorization of the CD19-targeted immunotherapy, tafasitamab, + lenalidomide (LEN) followed by tafasitamab monotherapy for patients (pts) with R/R DLBCL ineligible for autologous stem cell transplant (ASCT). Long-term L-MIND data further support the regimen. Here we present exploratory analyses of final 5-year (yr) efficacy in subgroups of interest. Methods: Pts (≥18 years) with ASCT-ineligible R/R DLBCL, 1–3 prior systemic therapies (incl. ≥1 targeting CD20) and ECOG PS 0–2 received tafasitamab for ≤12 28-day cycles (+ LEN), then alone until disease progression. Primary endpoint was objective response rate (ORR). Secondary endpoints included duration of response (DoR), progression-free survival (PFS) and overall survival (OS). Exploratory subgroup analyses including by International Prognostic Index (IPI) and time to progression after 1L (in pts with only 1 prior line) used Kaplan-Meier estimates of 5-yr endpoints. Results: As of 14 Nov, 2022 in the full analysis set (FAS; n=80), ORR was 56.2% [95% CI: 44.7–67.3]. Median treatment duration was 9.0 months (mo) [0.5–73.6] and median follow-up (mFU) for OS was 65.6 mo [59.9–70.3]). Median DoR was not reached (mFU: 43.7 mo [29.9–58.4]). Of 18 patients in follow-up for ≥5 years, 9 received tafasitamab until end of study per protocol, 9 discontinued while in remission. RR and 5-yr rates for DoR, PFS and OS showed long-term clinical activity in all pt subgroups (Table). Conclusions: In this 5-yr subgroup analysis, a long-term clinical benefit with tafasitamab + LEN followed by tafasitamab monotherapy was observed in all subgroups of clinical interest, including pts with poor prognosis risk factors. These data suggest this immunotherapy may have curative potential, which is being explored in further studies. Clinical trial information: NCT02399085 . [Table: see text]
Multicenter real-world study of newly diagnosed advanced-stage extranodal natural killer/T-cell lymphoma (ENKTL): Proposal for intensive therapy.
Authors: Wei Yu-Ce , Fei Qi , Zheng Bao-Min , Xie Yan , Chen Bo , Liu Wei-Xin , Zhang Changgong , Liu Weiping , Fang Hui , Qi Shunan , Zhang Di , Chai Yue , Li Ye-Xiong , Wang Wei-Hu , Song Yuqin , Zhu Jun , Dong Mei
Published: June 2023

e19523

Background: Advanced-stage ENKTL is characterized by its low prevalence, poor prognosis, and inconclusive optimal therapy. The present study investigated the treatment of newly diagnosed advanced-stage ENKTLs. Methods: Newly diagnosed stage III/IV ENKTL patients from two large-scale Chinese cancer centers in the last 10-15 years were retrospectively collected and analyzed. Results: With a median follow-up of 75.03 (range, 0.33-292.13) months, the median overall survival (mOS) for the 195 newly diagnosed stage III/IV ENKTL patients was 19.43 (range, 0.33-292.13) months, and estimated 1-, 2-, 3-, and 5-year OS were 59.5%, 46.3%, 41.8%, and 35.1%, respectively. First-line multi-modality therapy(n=89) significantly prolonged OS compared to single-modality therapy(n=106)( P<0.001). Chemotherapy(CT)+radiotherapy(RT)(n=47) compared to CT alone(n=93)( P=0.007), and hematopoietic stem cell transplantation(HSCT)(n=20) compared to non-HSCT(n=175)( P<0.001) both significantly improved OS. For patients ≤60 years and ineligible for HSCT, other therapies with complete remission(n=28) led to comparable OS( P=0.160), with no significant difference in baseline characteristics( P>0.05). Four long-term survival patients treated with chidamide maintenance therapy(MT) achieved a median progression-free survival(PFS) of 55.83(range, 53.27-92.33) months and a mOS of 60.65(range, 53.70-95.70) months, preliminarily indicating its positive impact on prognosis. Regarding CT, anthracycline(ANT)-based regimens(n=60), compared to non-ANT-based ones(n=119), led to significantly inferior PFS( P=0.031) and OS( P=0.010); while asparaginase(ASP)-(n=123) compared to non-ASP-(n=56), and gemcitabine(GEM)-(n=56) compared to non-GEM-based(n=123) regimens, both prolonged PFS( P=0.005; P=0.009) and OS( P=0.086; P=0.003). Multivariate analysis further showed that GEM-based regimens improved PFS(HR=0.691, P=0.061) and OS(HR=0.624, P=0.037) compared to non-GEM-based ones. The GEM+ASP(n=42) combinations slightly improved PFS and OS compared to regimens containing either GEM(n=14) or ASP(n=56) alone( P>0.05). The GEM+ASP combinations led to significantly superior PFS( P=0.058[log-rank test], P=0.036[Breslow test]) and OS( P=0.008) compared to the ANT+ASP combinations. First-line “intensive therapy”, including CT(particularly GEM+ASP regimens), RT, HSCT, and chidamide MT, was therefore proposed, and could improve long-term survival for advanced-stage ENKTLs. Conclusions: We propose the first-line “intensive therapy” for newly diagnosed advanced-stage ENKTLs, including CT, RT, HSCT, and chidamide MT. The GEM+ASP combinations appear to yield the optimal efficacy and survival. RT, consolidative HSCT, or chidamide MT are recommended.
Real-world treatment patterns of bruton tyrosine kinase inhibitors (BTKi) in patients with mantle cell lymphoma (MCL) in community oncology practices in the United States (US).
Authors: Shah Bijal D. , Xue Mei , Yang Keri , Liu Sizhu , Tang Boxiong
Published: June 2023

e19525

Background: Real-world data on BTKi use in MCL remain limited. This study aimed to examine US real-world BTKi treatment pattern, duration, and adherence in MCL patients. Methods: This retrospective observational study used electronic medical records (EMR) data from Integra Connect database in 18 US community-based oncology practices. Adults with MCL diagnosis on ≥2 separate dates who started BTKi therapy between 1/1/2019 and 11/30/2021 were included. EMR data was collected to ensure adequate medical history and ≥6-months follow up period. Index date was defined based on the use of one of the 3 BTKi: zanubrutinib, acalabrutinib, and ibrutinib for 3 BTKi patient cohorts. Baseline comorbidities were collected ≤90 days prior to index date based on diagnosis records. Sociodemographic and clinical characteristics, comorbidities, and treatment patterns were examined by each BTKi group. Treatment duration was calculated based on EMR and claims until end of follow up. Discontinuation data was based on unstructured physician notes. Kaplan-Meier analysis was used to compare treatment duration between the 3 BTKi groups. Results: In 402 MCL patients identified to start BTKi therapy (44 zanubrutinib; 161 acalabrutinib; 197 ibrutinib), the median age (range) at BTKi therapy start was 75 (56-89) years in zanubrutinib, 76 (36-89) in acalabrutinib, and 72 (36-89) in ibrutinib group ( P<0.01; Table). There is no significant difference between the 3 BTKi groups in other baseline characteristics. Half of zanubrutinib patients used other BTKi in prior therapy, with 31.8% switched from other BTKis to zanubrutinib ≤60 days of treatment start. In acalabrutinib group, 29% had prior BTKi use. Given a later approval date, zanubrutinib group had a relative shorter mean follow-up period (493 days [d]) vs acalabrutinib (701 d) and ibrutinib (746 d). Nevertheless, zanubrutinib patients had significantly longer median treatment duration (292 d) vs acalabrutinib (259 d) and ibrutinib (149 d) ( P<.01). Conclusions: Real-world EMR data from US community-based oncology practices suggested significantly longer treatment duration and adherence in MCL patients treated with zanubrutinib compared with acalabrutinib or ibrutinib. Further analyses on long term utilization are needed upon data maturation. [Table: see text]
Risk reduction of CNS relapse in diffuse large B cell lymphoma with intrathecal methotrexate prophylaxis: A single institution retrospective study.
Authors: Hino Christopher , Lacy Curtis , Brothers Joel M. , Cao Huynh Le , Mirshahidi Hamid R. , Park Kiwon , Akhtari Mojtaba
Published: June 2023

e19531

Background: Central nervous system (CNS) relapse is an infrequent but serious and challenging complication in diffuse large B-cell lymphoma (DLBCL) that carries a dismal prognosis. While several risk factors have been identified to stratify the risk for CNS relapse including the 2015 CNS internal Prognostic index (CNS-IPI), controversy still remains regarding the indication, timing, and method of CNS prophylaxis. The purpose of this study was to determine whether IT-MTX reduced the risk of CNS relapse, as well as treatment related and financial toxicity of CNS prophylaxis. Methods: We performed a single-center, retrospective analysis on a cohort of 192 patients with DLBCL who had received treatment between January 2010- August 2022. Patients were identified by using ICD10 code diagnosis in the electronic medical records system. We included patients of all stages of disease and CNS-IPI scores along with patients with testis, breast, sinus, and bone marrow extranodal involvement. Patients with primary CNS disease and primary mediastinal disease were excluded from the study. Clinical data collected by chart review included age at time of diagnosis, sex, performance status, LDH level, disease stage, number and type of therapies administered including IT-MTX, extranodal involvement, MYC/BCL2/BCL6 translocation status, HIV status, cell of origin (COO), treatment response. Toxicities and complications thought to be associated with IT-MTX prophylaxis were also documented in addition to total costs of treatment for each patient. Patient characteristics were compared using Fisher exact test or Pearson’s chi-square test. Results: In patients with intermediate to high CNS relapse risk (CNS-IPI 2-5) IT-MTX did not reduce the 1 year risk of CNS relapse (RR 1.1296, 95% CI 0.1933 to 6.6012, P = 0.08924). The median time to CNS relapse was longer in patients who had received IT-MTX (13.5 months) vs those who did not (7 months). Thirty eight (52.8%) patients reported adverse side effects of any kind as a result of IT-MTX administration, with 23.6% of patients developing grade 2-3 adverse events. The average cost for CNS-prophylaxis was estimated to be approximately $8,059.04 over a patient’s treatment course, but as high as $20,140. Conclusions: In conclusion, our study highlights the necessity to develop improved standardized guidelines for use of CNS prophylaxis in patients with DLBCL. The results from our retrospective study add to the growing body of literature showing IT-MTX has limited and potentially transient effectiveness in preventing CNS relapse. Given the high rate of side effects and significant cost of IT-MTX, we recommend that clinicians carefully consider the risks and benefits of prophylaxis before prescribing IT-MTX for CNS-prophylaxis.
Health-related quality of life and economic burden in Chinese patients with cutaneous T-cell lymphoma.
Authors: Wang Yang , Sun Jianfang , Sun Huiping , Zhang Mingzhi , Li Zhiming , Zhao Haifeng , Xie Linna , Huang Wenrong , Yan Xiaojing , Du Xiwen , Li Xiaojiao , Jin Hui , Shi Yuankai
Published: June 2023

e19533

Background: Cutaneous T-cell lymphoma (CTCL) is a rare type of non-Hodgkin lymphoma. As described in European Organization for Research and Treatment of Cancer Consensus, the subtypes of mycosis fungoides (MF) and Sézary Syndrome (SS) comprised roughly 55% and 5% of CTCL, respectively. The clinical presentations of MF and SS include skin lesion, tumors, ulcerations, systemic involvements and even death. This study aimed to measure the overall HRQoL and economic burden of MF and SS patients in China. Methods: A cross-sectional survey was conducted from 21 July 2022 to 24 October 2022. Eligible adult participants with a pathologically confirmed diagnosis of either MF or SS were recruited from specialty or general hospitals across China. All participants were asked to complete a questionnaire that assessed HRQoL and annual economic burden. Validated instruments in Chinese, specifically the EuroQoL Group’s five-level QoL five-dimensional questionnaire (EQ-5D-5L), Functional Assessment of Cancer Therapy-General (FACT-G), and Skindex-29, were used to assess general, cancer and skin-related HRQoL. All HRQoL outcomes were calculated using the scoring system provided by the institutions, and EQ-5D utility scores were mapped using the China time trade-off value sets. As for economic burden, it was investigated from the societal perspective, as the direct medical costs, direct non-medical costs, and productivity loss were all calculated. Results: A total of 61 patients were recruited and completed the survey. Patients resided in 38 cities of 21 provinces across China. 56 patients (92%) were diagnosed with MF and 5 (8%) with SS. 56% were male, with a mean age of 39 years. Half of the patients had early-stage disease (defined as less than stage IIB, patch or plaque), with the remainder having late-stage disease. Among the recruited patients, 43 (70%) received skin-directed therapy, and 55 (90%) received systemic therapy. As for HRQoL measures, EQ-5D utility score was 0.79 (±0.18), FACT-G score was 61.3 (±12.4), and the Skindex-29 score was 43.4 (±24.2). Comparison between patients with early-stage disease and late-stage is presented in the table. As for economic burden, the annual per capita cost for MF and SS patients was CNY 86,729 (USD 12,428), which greatly exceeded the annual disposable income in 2022 (CNY 36,883, equals USD 5,440). Conclusions: This was the first study investigating economic burden and HRQoL using patient-reported outcomes conducted in mainland China. The findings suggested that MF and SS has significantly compromised patients’ HRQoL and posed substantial economic burden. [Table: see text]
Diffuse large B-cell lymphoma in HHV8+ multicentric castleman disease: A national analysis of demographic features.
Authors: Whooley Maximillian , Keirns Darby , Wu Xinxin , Luker Andrew , Silberstein Peter T. , Hsia Beau
Published: June 2023

e19535

Background: Diffuse large B-cell lymphoma (DLBCL) in human herpesvirus 8 associated (HHV8+) multicentric Castleman disease (MCD) is a rare type of DLBCL. DLBCL, the most common non-Hodgkin lymphoma, is a cancer arising in the lymphatics. HHV8+ MCD is a lymphoproliferative disorder usually occurring in HIV patients. Patients who develop DLBCL in this setting typically die within a year. Prior National Cancer Database (NCDB) studies have assessed survival and demographics in the broader category of CD20- LBCLs, but have not specifically examined the socioeconomic and demographics associated with DLBCL in HHV8+ MCD. Methods: A retrospective analysis of NCDB data from 2010 – 2020 included patients diagnosed with DLBCL in HHV8+ MCD (N = 237). Demographic factors such as sex, race, Hispanic ethnicity, income status, insurance status, Charlson-Deyo score, facility type/location, and metastasis at diagnosis were evaluated with descriptive statistics. Primary site was also examined. Incidence trends were assessed via regression analysis. Results: A total of 237 patients with DLBCL in HHV8+ MCD were identified in the database, with an average incidence of 21.5 cases per year (R2 = 0.236, SD = 5.7, range = 9 – 29). 74.7% were male and the average age of diagnosis was 53.8 years (SD = 18.62, range = 3 – 90). 40 different primary sites were identified, with the most common being lymph nodes of multiple regions (32.9%). Extranodal primary sites were rare but documented. Charlson-Deyo comorbidity scores varied: Score 0 = 61.6%, Score 1 = 8.4%, Score 2 = 4.2%, Score ≥ 3 = 25.7%. Incidence for race was highest among Whites (69.2%), followed by Blacks (25.3%), then Asians (3.4%). 8.4% of patients were of Hispanic ethnicity. A greater percentage of patients were in the top income quartile (33.8%), compared to the second (19.7%), third (23.9%), and fourth (22.5%). Most patients were either insured privately or by Medicare (73.9%), whereas 8.9% were uninsured. Most were treated at academic facilities (54.7%), and many were treated at facilities in the Eastern United States (47.5%). 19.1% of patients had metastases at diagnosis, most often in distant lymph nodes (6.1%). Conclusions: This study provides insight into the demographics of patients diagnosed with DLBCL in HHV8+ MCD. This cancer showed a nearly 3-fold male preponderance and primarily affected Whites, mirroring existing trends in DLBCL overall. About one fifth of patients presented with metastasis at diagnosis. Interestingly, patient Charlson-Deyo scores displayed a bimodal distribution, with 87.3% of patients having a Score of either 0 or ≥3. The top income quartile was most affected, but patients were more evenly distributed among the bottom three. Further investigation is needed to better define the role of demographics in shaping diagnostic, therapeutic, and outcome discrepancies in those with DLBCL in HHV8+ MCD.
High dose methotrexate (MTX) treatment: Value of post treatment MTX level monitoring and risk factors for acute kidney injury.
Authors: Snyder Rose , Urazov Anna , Deh Mayukh , Kulkarni Ajinkya , Chen Pin-Jung , Raju Gagan , Tanni Miss , Xu Yiqing
Published: June 2023

e19539

Background: High-dose methotrexate therapy is an effective treatment for primary central nervous system (CNS) lymphoma and other tumors. Methotrexate (MTX) is an antimetabolite which penetrates blood brain barrier when administered intravenously at high doses. Defective or delayed clearance of MTX may lead to toxicities, especially acute kidney injury (AKI) in 2-13% of patients. We developed a protocol to mitigate side effects by checking MTX levels every 24 hours, administering leucovorin or glucarpidase rescue, and hydration with urine alkalization. This study examines the risk factors for developing AKI after high dose MTX administration. Methods: Patients who began treatment with high dose methotrexate in 2020 and 2021 were eligible. We collected data on demographics, diagnosis, methotrexate levels, laboratory levels at baseline and after treatment, toxicities, interventions and outcomes. Results: 26 patients were included, who received 112 cycles of treatments (median 3.5, range 1-10). Median age was 62 years (range 25-83) and 57% were male. 20 patients experienced elevated MTX levels. Among the 112 cycles, MTX levels were elevated at 24h, 48h and 72h in 22 (19.6%), 16 (14.3%), and 45 (40.2%) of the cycles respectively, which trigged an increase in the rescue leucovorin dose and hydration dose in 26 (23.2%) and 16 (14.3%) cycles, respectively. AKI was recorded in 20 cycles (17.9%), with 17 (85%) being grade 1 (ULN – 1.5 x ULN), and 3 (2.7%) being grade 2 (1.5-3x ULN). In 20 cycles with AKI, 9 (45%) had grade 1 elevated creatinine level pretreatment; 8 (88.9%) of them remained grade1 without increase > 0.2. The development of AKI occurred in all MTX dose levels, without a difference in frequency. 57% of cycles with elevated 24h MTX level, and 13% of cycles with delayed clearance > 4 days, were associated with AKI. 75% of cycles with AKI had delayed clearance (avg 7 days). Two patients required glucarpidase rescue treatment, based on elevated 24-36 h MTX level and grade 1-2 AKI; one of these patients permanently discontinued MTX. Conclusions: Among 26 patients who received a total of 112 cycles of high dose MTX treatment, 11 developed AKI in 20 cycles, mostly grade 1 with spontaneous recovery. MTX level elevation at 24 hours predicted the development of AKI. Elevated baseline creatinine or MTX dose range is not a risk factor for AKI.
Epidemiology and prognostic factors of hepatosplenic T-cell lymphoma (HSTL): An analysis of NCDB (National Cancer Database).
Authors: Albagoush Sara , Masih Durva , Cichon Gregory , Cogua Laura , Silberstein Peter T. , Ermann Daniel Arthur
Published: June 2023

e19544

Background: Hepatosplenic T-cell lymphoma (HSTCL) is a rare T-cell malignancy, associated with rapid disease progression and generally poor outcomes. To date, few studies have been performed that examine outcomes expected survival outcomes and clinical features of this disease. We aimed to perform a large retrospective study with a focus on disease characteristics and overall survival outcomes. Methods: Utilizing the National Cancer Database (NCDB), we identified 434 patients with HSTCL 2004-2020. Patients were selected by ICD-0-3 histology code 9716. Kaplan-Meier curves and survival tables were created to calculate 1-, 5-year survival probabilities for variables including ages, race, sex, facility type, age, insurance, primary site, stage, and adjuvant therapy. Log-rank and cox regression analysis was used to compare the groups within each variable. Results: The cohort consisted of 68.9% male patients and 67.4% Caucasian patients with a median age of diagnosis of 50 years old. The most common type of insurance was private insurance 49.5% then Medicare 24%, Medicaid 16.4% and not insured 5.8% with median distance of 16.1 miles from hospital where they received care. Most patients (56.8%) were treated at academic/ research facilities, followed by comprehensive community cancer programs 22.8%. Mostly located in metro areas (85.5%) with median household income > $ 46000 (43.5%). More cases diagnosed since 2013. The most common primary anatomical site was spleen 91.7% followed by lymph nodes. Stage IV was the most common stage 77.2%t. Overall, 1-, 5- year survival probabilities for patients with HSTCL were 47.4% and 25.4% respectively. Median overall survival time is 11.24 months (95% CI 9.592-12.888). Female patients had better survival outcomes than males with median survival 20.6 months and 9.5 months, respectively. Academic/research centers (12.65 months) and Medicaid (14.98 months) followed by private insurance (11.79 months) had better survival outcomes. As stage increased, overall survival probabilities decreased; stage 1 median survival 12.71 months, stage 4 (11.24 months). Spleen (12.35 months) had better survival outcomes compared to lymph nodes. With regards to treatment modalities, patient who underwent bone marrow transplant (81.64 months) followed by surgery of primary site (14.92 months) followed by multiple agent chemotherapy (11.27 months) had better survival rates compared to all other treatment modalities. Conclusions: This is the largest and most comprehensive study to date on the epidemiology and prognostic factors of Hepatosplenic T cell Lymphoma. The result of our analysis brings up several interesting trends including females had significantly longer survival when compared to males with the same disease. Other major factors influencing survival are facility type, age, sex, race, insurance status, stage, adjuvant therapy and primary site.
Clinical outcomes of patients with multiple myeloma following disease progression after BCMA-targeted CAR T-cell therapy.
Authors: Subramanian Naveen G. , Garcia Pleitez Hector , Pasvolsky Oren , Kalariya Nilesh , Patel Krina K. , Ferreri Christopher J.
Published: June 2023

e20002

Background: While BCMA-targeted CAR T therapies have yielded unprecedented efficacy in patients with multiple myeloma, most patients (pts) experience disease relapse. Treatment after progression on CAR T has become an unmet need given the limited novel treatment options available. We evaluated clinical outcomes for pts relapsing after BCMA CAR T. Methods: This was a single-center retrospective analysis including pts who had been treated with a BCMA-targeted CAR T therapy prior to 12/31/22 and then had disease progression. Data for all subsequent lines of therapy were collected, and best response to therapy was graded as per IMWG criteria. Statistics were descriptive in nature. Results: Thirty pts treated with BCMA CAR T (14 trial, 16 commercial) relapsed. The cohort of median age 61 had notable disease characteristics of 40% with high-risk FISH and 30% with extramedullary disease (EMD). The median number of prior lines of therapy (LOT) was 5, with 80% triple-class refractory and 47% penta-refractory. Patients treated with late BCMA CAR T (≥ 4 prior LOT; n=20) had higher rates of EMD (40% v 10%), triple-class refractory (90% v 60%), and penta-refractory disease (55% v 30%) compared to pts who received early CAR T (< 4 prior LOT; n=10). At data cutoff, 4 pts died without receiving subsequent therapy and 1 pt was pending start of their first regimen. The remaining 25 pts received 58 salvage therapies, of which 54 regimens were evaluable for response. The overall response rate (ORR) for all regimens was 46%. Median overall survival (OS) was not reached, and the 6 and 12-month OS rates were 83% and 77% respectively. ORR and median progression free survival (PFS) stratified by the specific type of salvage therapy are shown in the table. Patients who received a regimen consisting only of agents they had received in a prior LOT had an ORR of 57% and median PFS of 3.6 months. Patients who received early CAR T had a higher ORR to all subsequent salvage therapies (59% v 33%), longer median PFS (4.6 months v 1.6 months), and higher 12-month OS (90% v 70%). Conclusions: For pts with progression after BCMA CAR T, treatment with another BCMA CAR T or transplant had more favorable outcomes. Retreatment with prior therapies resulted in disease control for a fair number of patients, which can serve as a bridge to another novel therapy. The pts treated with early CAR T had more favorable post-progression outcomes than late CAR T, yet 70% of pts who received late CAR T were alive at 1 year post-progression. [Table: see text]
A perilous and complicated situation in hospitals: Vitamin D deficiency in multiple myeloma patients—A nationwide cross-sectional study.
Authors: Lakhanpal Manisha Rakesh , Chelikam Nikhila , Manjani Divesh , Lahori Simmy , Akella Sai Anusha , Shivashankar Prashanth Gumpu , Shah Shlok Vimal , Ali Abdirazak , Toor Varneet , Singh Aryak , Gujarathi Rahul , Manjani Lokesh , Patel Urvish , Adiga Avinash , Kukreja Geetika
Published: June 2023

e20010

Background: For the year 2019, the United States age-adjusted rate of new Multiple Myeloma (MM) cases was 6.8 per 100,000 people and the age-adjusted death rate was 3 per 100,000 people. Vitamin D Deficiency (VDD) and associated complications are very common in MM patients. Aim of our study was to evaluate the prevalence and risk of VDD in patients with MM and VDD associated disability and mortality in the VDD patients. Methods: We performed a cross-sectional retrospective analysis of Nationwide Inpatient Sample data 2016-2018. Adults hospitalizations with MM were identified using ICD 10 code. Hospitalized patients were grouped into patients with VDD and without VDD. We ran chi square, unpaired-t test and mixed-effect survey logistic regression analysis to find out odds ratio and 95%CI showing outcomes of VDD in MM patients. Results: We found 330,175 hospitalizations with MM. Of these 11,480 were noted to be patients with VDD with higher prevalence (0.64% vs 0.37%) of and strong association (aOR:1.41, 95%CI:1.35-1.47) with MM in comparison without MM. Amongst MM, females [1.50, 1.49-1.51], black race [1.23, 1.22-1.24], urban teaching hospitals [1.22, 1.22-1.23], and hospitals in mid-west region [1.30, 1.29- 1.32] had higher prevalence odds of VDD compared with males, white race population, rural hospitals and hospitals in northeast region. (p<0.0001) Patients with VDD had higher prevalence and strong association with higher morbidity [5.1% vs 3.9%, 1.24,1.14-1.36; c-value=0.67], severe/extreme disability [77.2% vs 73.3%, 1.26, 1.20-1.33; c-value=0.73], and discharge to locations other than home [51.15% vs 45.69%, 1.29, 1.23-1.34; c-value=0.69] in comparison without VDD. (p<0.0001) [Table]. Conclusions: Significant poor outcomes warrant early identification of VDD and role of same hospitalization vitamin D replacement amongst MM patients with higher risk. [Table: see text]
External validation of venous thromboembolism risk prediction models in patients with multiple myeloma in a community setting: A retrospective cohort study.
Authors: Ramasamy Chidambaram , Sekar Abinesh , Shanmugavel Geetha Harinivaas , Kumar Madhan Srinivasan , Syed Masood Pasha , Seetharaman Kala , Siddiqui Ahmad Daniyal , Abraham George M.
Published: June 2023

e20027

Background: Newly diagnosed Multiple Myeloma (MM) patients have a 10 to 20 times higher risk of developing venous thromboembolism (VTE) than the general population. Three risk prediction models have been recently established to ascertain the degree of VTE risk: SAVED (Surgery, Asian race, VTE history, Elderly and Dexamethasone), IMPEDE VTE (Immunomodulatory drugs (IMiD), BMI, Pelvic fracture, Erythropoietin stimulating agent, Dexamethasone/Doxorubicin, Asian Ethnicity, VTE history, Tunneled line, Existing thromboprophylaxis) and PRISM scores (Prior VTE, Race, IMiD, Surgery, Metaphase Cytogenetics). Our primary objective was to assess the external validity of three VTE risk prediction models in a community hospital setting. Methods: All consecutive newly diagnosed MM treated at Saint Vincent Hospital from 1/1/2012 to 12/22/2022 were included in our analysis. Patients receiving therapeutic anticoagulation for other indications or a diagnosis of VTE within 6 months prior to MM diagnosis were excluded. Variables were collected by retrospective chart review at the time of MM treatment initiation. Model discrimination was assessed by calculating the area under the receiver operating characteristic curve (AUROC). Logistic regression was used to calculate the odds ratio (OR) of VTE occurrence with candidate variables in the risk prediction model. Results: The 160 patients with newly diagnosed MM and available data on VTE occurrence were included. The median age of our cohort at treatment initiation was 74 years (range 31-96); 55% were male, and 75% were Caucasians. IMiD-based induction regimen was used in 68.1 % of patients. The median SAVED score was 1 (IQR:0-2), IMPEDE VTE was 4 (IQR: 2-6), and PRISM score was 2 (IQR: 0-2). The most common thromboprophylactic agent used was aspirin (53.8%). The median time to VTE from induction was 4.8 months. The cumulative incidence of VTE at 12 months was 13.1%. Each 1-point increase in the score was associated with a significantly higher chance of VTE occurrence across all three models (Table). Factors significantly associated with the development of VTE were prior VTE history (OR:2.28, 95% CI:1.31-3.97,p = 0.003) and age greater than 80 years (OR:4.03, 95% CI:1.47-11.02,p = 0.006). Conclusions: Our findings suggest that all three PRISM (AUROC = 0.70), SAVED (AUROC = 0.72), and IMPEDE VTE (AUROC = 0.73) scores could statistically predict VTE outcomes in our patient population. The inclusion of more parameters in the IMPEDE VTE score may have led to its outperformance in risk stratification. [Table: see text]
Trends in presentation, treatment, and survival in young multiple myeloma patients age 50 and under from 2000-2021.
Authors: Kumar Anupama Deepa , Quan Michelle Alyssa , Costello Caitlin , Aaron Rosenberg
Published: June 2023

e20028

Background: Multiple myeloma (MM) is a disease predominantly of older adults with an average age of 69 at diagnosis. Limited data is available on the diagnostic details and outcomes of MM patients ≤50 years old, and particularly how these trends have changed over the past two decades. We present data from one of the largest retrospective cohorts of younger MM patients. Methods: This retrospective review identified 213 MM patients by pooling two datasets: 88 MM patients aged ≤50 years at first stem cell transplant (SCT) between 1/1/2000-6/1/2021 at University of California (UC), San Diego; and 125 MM patients age ≤50 years old at diagnosis between 1/1/2014-7/1/2021 at UC Davis. Demographics, diagnostic details, treatment, response, and overall survival (OS) data were collected. Results: The pooled dataset included 209 patients with MM and 4 with plasma cell leukemia. The median age was 45, with 58 (27%) Hispanic and 37 (17%) Black patients. In 89 patients with available data, 23% were R-ISS-1, 58% were R-ISS-2, and 19% were R-ISS 3. Overall, 14% of patients had high-risk cytogenetics [ t(4;14), del17p, or t(14;16]] . Patients diagnosed and treated in 2000-2010 were more likely to have received doublet or cytotoxic chemotherapy for induction therapy, while 80% of patients in 2010-2021 received triplet-based therapies. Responses to induction improved across decades, with 23% of patients in the earlier cohort vs 49% patients in the later cohort achieving a very good partial response (VGPR) or better. Eighty-five percent of patients received a SCT, the majority being autologous with only 13 upfront or salvage allogeneic SCTs in the earlier and 1 in the later cohort. The median OS for the entire cohort is 168 months, 171 months in the early cohort, and not reached in 2011-2021 cohort. Conclusions: We present retrospective data of a large and diverse cohort of California MM patients ≤50 years old, with nearly 50% of patients from underrepresented populations spanning over 2 decades. We found similar diagnostic features and risk group to those reported in the general MM population. Noticeable improvements in treatment responses were seen in the later decade with the introduction of modern therapies. A median OS of 14 years for the entire cohort over 20 years offers a glimpse into the hopeful promise for extended survival of younger patients as more effective therapies lead to deeper and more durable responses. [Table: see text]
Pitfalls with analyses of real-world data: A look at ASCO’s CancerLinQ Discovery Multiple Myeloma dataset.
Authors: Shou Karen J , Thornton Jennifer A , Sunderland Kevin , DeStefano Christin
Published: June 2023

e20033

Background: Real world data (RWD) are increasingly used in oncology research. Yet, a big limitation of RWD is missing data, potentially generating misleading conclusions. Methods for handling missing data include excluding patients with missing variables, using machine-based or statistically-imputed values, or using proxies (surrogates). Another limitation deals with excluding deaths at time zero, which may lead to misleading conclusions when analyzing survival of patients with aggressive cancers. This work highlights the impacts data exclusion, variable surrogacy, and death at time zero have on survival analysis results. Methods: ASCO’s CancerLinQ Discovery Multiple Myeloma (MM) dataset was used to assess overall survival (OS) in patients with MM diagnosed from 2009-2021. Of the 34,234 patients included in the actual analyses, 3,582 (10%) were missing a recorded date of MM diagnosis. In these cases, dates of first anti-myeloma therapy were used as surrogates since most MMs are treated at diagnosis. OS was compared between MM patients with “known” vs. surrogate or “presumed” diagnosis dates. To assess how the inclusion of deaths at time zero may or may not affect OS, the data were first analyzed by excluding patients who died within 1 month of second primary malignancy (SPM) diagnosis, including secondary AML (sAML). A second analysis of the same sample added a constant (0.5) to all survival times, allowing for inclusion of patients who died within one month of diagnosis. Analyses were conducted with STATA Version 17.0 (College Station, TX). Results: Despite the strong, positive correlation between recorded MM diagnosis date and date of first anti-myeloma therapy, there was a statistically significant difference in survival of MM patients with a known vs. presumed date of diagnosis (median OS 115 vs. 45 months, HR 2.54, 95% CI 2.41-2.69, p < 0.001). Dropping vs. including deaths within one month of diagnosis resulted in a marked difference (i.e., nearly 1 year) in median OS from the date of diagnosis of any SPM (113 vs. 103.5 months) as well as sAML (41 vs. 30.5 months). Conclusions: Although RWD hold promise, oncologists must be aware of common pitfalls in survival analyses: missing data, variable surrogates, and deaths at time zero being dropped. Patients with a recorded date of MM diagnosis appear to be fundamentally different from those who don’t have a date of diagnosis but do have a date of anti-myeloma therapy recorded. For aggressive malignancies, excluding patients who died at time zero can lead to over-estimation of survival. Adding a small constant (0.5) to the time variable can enable the inclusion of patients who die quickly after their cancer diagnosis. In conclusion, when utilizing RWD to guide clinical decision making, it is important to be aware of common threats to data validity, which can produce misleading results.
Health-related quality of life among patients with multiple myeloma treated with CAR-T therapy.
Authors: Gagnon Samantha Jane , Nooka Ajay K.
Published: June 2023

e20040

Background: The regulatory approvals in myeloma were predominantly based on the safety and efficacy of the antimyeloma therapies. Health-related quality of life (HRQOL) metrics have not routinely been incorporated into these studies, nor were they a requirement for approval, which explains the dearth of HRQOL studies in myeloma. Recent approvals of chimeric antigen receptor T-cell (CAR-T) therapy targeting the B-cell maturation antigen were no different. While improved clinical outcomes in myeloma led to the FDA and EMA approvals, the CAR-T effects on HRQOL are not well described. Methods: We conducted a cross-sectional observational pilot study to evaluate HRQOL among patients that received CAR-T. Inclusion criteria were age >/= 18 years with a diagnosis of myeloma, had been treated with an autologous CAR-T a minimum of 56 days prior to survey date and had not yet experienced progression as defined by the IMWG criteria. HRQOL measurements were obtained using validated tool, self-administered FACT-MM questionnaire post-CAR-T infusion. The primary endpoint measurement was the FACT-MM composite score. Associations between FACT-MM scores and predictors were analyzed using nonparametric tests. FACT-MM and subscores were analyzed as continuous and dichotomous outcomes. Results: Between December 2021 and July 2022, 22 patients were enrolled (male: 54.55%, white: 54.55%). The median age of patients was 64 (range, 43-86) and the median time to enroll on the study from diagnosis is 6.5 years (3.5-17). Median FACT-MM score was 137.5 (IQR: 18.5) out of a maximum possible score of 164. The median trial outcome index (TOI) which is the sum of the physical and functional well-being (PWB and FWB), a predictor for physical and functional outcomes from treatment (FACIT) was 95 (IQR: 17) out of maximum possible 112. Other descriptive variables of interest were shown in the table. Differences in TOI were found between races (White, African American (AA), & Asian p = 0.04). In our sample, AA and Asian subjects had higher median TOI, therefore race should not be considered to have a negative impact on clinical trial success. Subjects with a history of Gilbert’s syndrome (2 vs 20), reported higher overall FACT-MM scores (p = p=0.04), PWB (p=0.03) and pain-related HRQOL (p = 0.04). Interestingly, we did not find that HRQOL differed by patients that had evidence of CRS or ICANS during CAR-T therapy, or by age, R-ISS, CCI, presence of EMD or prior lines of therapy (LOT). Conclusions: Patients treated with CAR-T have reported high HRQOL metrics at least 2 months out from infusion. Age, RISS, CCI, prior LOT did not impact the HRQOL and may not be the sole criteria used for decision making whether or not to offer CAR-T. [Table: see text]
Non-vitamin k oral antagonists versus aspirin for primary thromboprophylaxis in patients with multiple myeloma on outpatient chemotherapy: A systematic review and meta-analysis.
Authors: Costa Thomaz Alexandre , Costa Bruno Almeida , Felix Nicole , Godoi Amanda , Nogueira Alleh , Richter Joshua Ryan , Rossi Adriana
Published: June 2023

e20041

Background: Patients with multiple myeloma (MM) are at an elevated risk of venous thromboembolism (VTE), which is further increased in patients receiving immunomodulatory drugs (IMiDs). Current guidelines suggest that non-vitamin K oral anticoagulants (NOACs) may be an alternative to low-dose aspirin (ASA) for primary thromboprophylaxis in this population. However, there is limited data comparing these two antithrombotic therapies among MM patients undergoing treatment with IMiDs. Methods: We performed a systematic review and meta-analysis to compare NOACs with ASA for primary thromboprophylaxis in individuals with newly-diagnosed or relapsed/refractory MM undergoing outpatient chemotherapy with an IMiD-based regimen. PubMed, Cochrane, and EMBASE were systematically searched from inception to January 2023. Observational studies and randomized controlled trials were included when comparing NOACs versus aspirin for thrombotic and hemorrhagic outcomes. Statistical analysis was performed with Review Manager 5.4.1. Results: We included 10 randomized controlled trials and observational studies comprising 1026 MM patients who underwent primary thromboprophylaxis with NOACs (33%) or ASA (67%). Thromboprophylaxis with NOACs was associated with a significantly lower incidence of VTE compared with ASA (OR, 0.33; 95% CI, 0.16-0.68; p < 0.001; I² = 0%). Each group had one major bleeding event, with no statistically significant difference between NOACs and ASA (OR, 1.35; 95% CI, 0.05-35.51; p = 0.86; I² = 51%). Similarly, clinically relevant non-major bleeding (OR, 0.56; 95% CI, 0.12-2.70; p = 0.47; I² = 0%) and minor bleeding (OR 1.48; 95% CI: 0.42-5.24; p = 0.54; I² = 0%) event rates did not differ significantly between groups. Conclusions: These findings suggest that NOACs may be superior to ASA for VTE prophylaxis among MM patients receiving IMiD-based chemotherapy, with no significant difference in the overall bleeding risk between the two groups.