bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics of patients with myelofibrosis on ruxolitinib for three or more years.
Authors: Masarova Lucia , Bose Prithviraj , Pemmaraju Naveen , Chifotides Helen T. , Zhou Lingsha , Estrov Zeev , Kantarjian Hagop M. , Verstovsek Srdan
Published: June 2022

e19082

Background: Ruxolitinib (RUX) was the first JAK1/2 inhibitor approved for patients with advanced phase of myelofibrosis (MF) with median therapy duration of about 3 years. We aimed to characterize clinical features of patients treated with RUX for ≥3 years who presented to our institution between January 2000 and January 2019. Methods: Retrospective review of medical records of 131 patients who received RUX for ≥3 years. Clinical characteristics, therapy details and overall survival (OS; Kaplan Meier method) were assessed at/from the time of RUX initiation. Cox proportional hazard model was used for univariate (known clinical variables) and multivariate analysis (p < 0.05 on previous analysis) of factors associated with OS. Results: Median age of patients was 67 years (range, 31-84), 56% were males (clinical characteristics in Table). Among 62 patients with ≥ 28 gene next generation sequencing; 19, 24 and 19 patients had none, 1 and ≥2 mutations beyond JAK2, MPL, CALR, respectively. Eighty four percent of patients received RUX as frontline therapy. Median time to RUX from presentation and from MF was 4 (range, 0.1-123) and 11 months (range, 0.1-228), respectively. Starting dose of RUX was ≥ 15 mg, 10 mg and 5 mg twice daily in 110 (84%), 17 (13%), and 4 (3%) patients, respectively. Median duration of RUX therapy was 76 months (95% CI, 56-88). At the time of last follow-up (median duration of 104 months; 95% CI, 93-115), 44 patients (35%) were on RUX. Reasons for discontinuation in the remaining patients included MF progression (n = 54; 62%), blastic phase (n = 7; 8%), cytopenias (n = 4; 5%) and unrelated causes (n = 22, 25%). Median OS since therapy start was 90 months (95% CI, 76-104) with 40% of patients being alive at 10 years. Patients ≥ 65 years had median OS of 76 months (95% CI, 67-85). Patients with intermediate 2 (n = 81) or high risk (n = 29) DIPSS at RUX start had median OS of 89 (95% CI, 71-107) and 72 (95% CI, 55-89) months, respectively. Factors affecting OS on univariate analysis (HR, 95% CI, p-value) were age > 65 years (2.56, 1.49-4.35, < 0.001), neutrophils % (0.97, 0.95-0.99, 0.006), blasts % (1.213, 1.035-1.421, 0.017), performance status of <2 (0.228, 0.069-0.752, 0.015). The only factors retaining significance on multivariate analysis were age > 65 years (2.7, 1.50-4.14, < 0.001) and neutrophils % (0.66, 0.29- 0.86, 0.012). Conclusions: Forty percent of patients who remained on RUX for ≥3 years were alive at 10 years since their therapy initiation. Age remains the major predictive factor of survival despite long RUX therapy.[Table: see text]
Erdheim-Chester disease: An orbital MRI study.
Authors: Haroche Julien , Gueniche Yoram , Galanaud Damien , Cohen-Aubart Fleur , Dormont Didier , Rousseau Théophile , Spano Jean-Philippe , Amoura Zahir , Touitou Valerie , Shor Natalia
Published: June 2022

e19085

Background: Erdheim-Chester disease (ECD) is a rare L-group histiocytosis. Orbital involvement is found in a third of cases, but few data are available concerning the radiological features of ECD-related orbital disease (ECD-ROD). Our aim was to characterize the initial radiological phenotype and outcome of patients with ECD-ROD. Methods: Initial and follow-up orbital MRI from the patients with histologically proven ECD at a national reference center were reviewed. Results: Pathological orbital findings were recorded for 45(33%) of the 137 patients included, with bilateral involvement in 38/45 (84%) cases. The mean age of these patients was 62 years (24-81) and 78% were men. Intraconal fat infiltration around the optic nerve sheath adjacent to the eye globe (52%), with intense gadolinium uptake and fibrous component was the most frequent phenotype described. Optic nerve signal abnormalities were observed in 47% of cases. Two patients presented bilateral homogeneous extraocular muscle enlargement suggestive of the myositis type of ECD-ROD. None had isolated dacryoadenitis. Only seven patients (15%) had normal brain MRI findings. ECD-associated paranasal sinus involvement and post-pituitary involvement were detected in 56% and 53% of patients respectively. A decrease/disappearance of the lesions was observed in 17/24(71%) of the patients undergoing late follow-ups. Interestingly, ECD-ROD only rarely (7/45(16%)) revealed the disease, with exophthalmos being the most frequently identified feature in this subgroup (3/45 (6%)). Conclusions: Even though ECD-ROD can be clinically silent, it constitutes a broad array of lesions often resulting in optic nerve signal abnormalities, the functional outcome of which remains to be established. ECD-ROD should thus be assessed initially and subsequently monitored by orbital MRI and ophthalmological follow-up.
Anti-CD19 chimeric antigenic receptor T cell as a second-line therapy for patients with relapsed/refractory diffuse large B-cell lymphoma.
Authors: Naqvi Syed Arsalan Ahmed , Asghar Noureen , Sipra Qurat Ul Ain Riaz , Paludo Jonas , Riaz Irbaz Bin , Husnain Muhammad
Published: June 2022

e19502

Background: Inconsistent results observed in recent trials (ZUMA-7, TRANSFORM, BELINDA) assessing chimeric antigenic receptor T (CAR-T) cell therapy in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) prompted a meta-analysis to assess the available evidence and to compare the effectiveness of different CAR-T products. Methods: MEDLINE and EMBASE were searched to identify full-text or abstract publications of phase 3 randomized controlled trials (RCTs) assessing CAR-T in patients with R/R DLBCL compared to standard of care (SOC). Efficacy outcomes included event-free survival (EFS), progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and complete response (CR). CR rates were also compared between CAR-T and patients in SOC arm who received autologous stem-cell transplantation (ASCT). Safety outcomes included grade > 3 any adverse events (AE), cytokine release syndrome (CRS) and neurological toxicity (NT). A DerSimonian-Laird random-effects meta-analysis was conducted to pool effect estimates. Freeman-Tukey transformation method was used to estimate pooled proportion (PP) of safety events specific to CAR-T. Mixed treatment comparisons were computed using a frequentist network meta-analysis approach. Results: Of 1803 studies identified, three RCTs with 865 patients were included. Meta-analysis showed significant improvement in EFS (HR: 0.51; 95% CI: 0.27-0.97; I2: 92%), PFS (HR: 0.47; 95% CI: 0.37-0.60; I2: 0%) with CAR-T compared to SOC. OS was not significantly different between the two groups (HR 0.76; 95% CI: 0.56 to 1.03; I2: 29%). Higher objective response (RR: 1.49; 95% CI: 1.13-1.97; I2: 81%), and CR rates (RR: 1.55; 95% CI: 1.07-2.24; I2: 79%) were observed with CAR-T compared to SOC. However, CAR-T was associated with lower CR when compared to patients who underwent ASCT (RR: 0.65; 95% CI: 0.46-0.90; I2: 89%). The safety profile was not different between CAR-T and SOC. The incidences of grade ≥3 CRS (PP: 4.19; 95% CI: 1.60-7.80; I2: 57%) and grade ≥3 NT (PP: 7.57; 95% CI: 0.20-22.6; I2: 95%) were low. Mixed treatment comparisons showed significant EFS benefit with liso-cel (rank 1: HR: 0.37; 95% CI: 0.22-0.61) and axi-cel (rank 2: HR: 0.42; 95% CI: 0.29-0.61) compared to tisa-cel (rank 3). No significant differences were observed among different CAR-T products for PFS or OS improvement. The safety profile of CAR-T products was comparable with tisa-cel (rank 1) being the safest. Conclusions: CAR-T therapy, as a second line treatment, appears to be effective in achieving higher response rates and delaying the disease progression compared to SOC in R/R DLBCL. However, given lack of OS benefit coupled with lower response rates when compared to patients who received ASCT, we should exercise caution in adopting CAR-T as second line therapy for all patients with R/R DLBCL.
Role of anakinra in the management of icans after CAR T-cell therapy for lymphoma.
Authors: Munugala Nishant , Dashkevych Ulyana , Husnain Muhammad
Published: June 2022

e19506

Background: Chimeric antigen receptor (CAR) T-cell immunotherapy is a revolutionary treatment modality which has gained attention for its potential in treating multiple refractory hematological malignancies. Significant toxicities associated with CAR T- cell therapy remain a major concern. Cytokine release syndrome (CRS) and Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS) are seen early on post CAR-T cell therapy. To date, the treatment of ICANS has largely been limited to supportive care and corticosteroids. More recently, some early clinical data investigated the use of Anakinra as a promising agent in prevention and treatment of severe ICANS. Methods: We analyze three cases in which Anakinra was used to treat high-grade ICANS concurrently with high dose steroids. Results: A 51-year-old woman with high grade DLBCL and secondary CNS involvement was treated with Tisagenlecleucel CAR-T therapy. On day 2, patient became altered and was diagnosed with ICANS Grade II. High dose steroids were started leading to resolution of ICANS. However, patient’s mentation worsened by day 7, progressing to ICANS Grade IV by day 8, and Anakinra 100 mg IV was added to the steroid regimen. By day 11, after 4 doses of Anakinra, patient’s neurotoxicity completely resolved. Patient achieved a PR by day 30 after CAR-T cell infusion. In the second case, a 65-year-old man with DLBCL and leptomeningeal involvement developed ICANS Grade II on day 1 after Tisagenlecleucel CAR-T therapy and was started on high dose steroids. By day 4, neurotoxicity worsened and progressed to ICANS Grade IV. On day 5 patient was transferred to ICU for a mechanical ventilation, and Anakinra 100 mg IV was added and continued daily for 7 days. By day 12, neurotoxicity improved to ICANS grade II and patient was extubated. Meanwhile, high dose steroids were tapered. His condition acutely worsened by day 19, prompting transfer to the ICU and re-initiation of Anakinra concurrently with steroids. His family decided against further escalation of care on day 22. Patient was transitioned to comfort care and died 23 days post CAR-T cell infusion. In the third case, a 65-year-old man with mantle cell lymphoma was treated with Brexucabtagene autoleucel CAR-T therapy. On day 8, patient developed ICANS Grade I which rapidly progressed to Grade IV. High dose steroids were started and ICANS improved to Grade II on Day 9. However, on Day 10 patient’s mentation again worsened and one dose of Anakinra 100mg IV was added to the steroid regimen. By day 11, ICANS completely resolved, and patient was ultimately discharged home on day 15. Patient was able to achieve interval CR by day 30 after CAR-T cell infusion. Conclusions: In the reported cases, ICANS improved following administration of Anakinra, adding support to the idea that Anakinra may be beneficial in treatment of high-grade ICANS. Future studies are needed to better understand the overall efficacy and the ideal timeline for administration.
Outcomes of Richter’s syndrome in patients with chronic lymphocytic leukemia (CLL) treated with platinum or anthracycline based chemotherapy with or without a BTK inhibitor (BTKi).
Authors: Alasfour Maryam , Pongas Georgios , Jones Sandra , Alawadi Salman , Plate Thomas
Published: June 2022

e19511

Background: Richter’s syndrome (RS) is a rare complication of chronic lymphocytic leukemia (CLL) and the median survival is generally poor. Evidence is limited regarding the biology of the disease, treatment and outcomes. Methods: We retrospectively reviewed pts diagnosed (dx) with pathologically confirmed RS who presented at the University of Miami Sylvester Cancer Center between 2011 and 2020. Informed consent was provided through IRB-approved protocols. Descriptive statistics were utilized and overall survival (OS) was calculated from RS diagnosis to death or last follow-up by Kaplan-Meier. Results: 33 patients with RS, including 87.9% diffuse large B-cell lymphoma-type RS and 12.1% Hodgkin lymphoma-type RS were identified. Median time from CLL dx to RS transformation was 37months (m). Most patients presented with elevated LDH 75%, bulky lymphadenopathy 66%, and adverse genetic features, such as TP53 disruption 52% or complex karyotype 81%. FISH at RS dx: del(17p) 37%, del(11q) 17%, trisomy 12 58%. ORR to first line therapy was 75.8% (55% CR, 27% PR), but of those who achieved CR, 44% relapsed. Median PFS (mPFS) was 10m for the anthracycline-based chemotherapy group (ABC) with a CR of 50%, compared to 15.5 m for the platinum-based chemotherapy group (PBC) and a CR of 60%. Similar OS were observed regardless of the chemotherapy regimen with median OS (mOS) of 60 m in the ABC group vs 59.5 m in the PBC group. Notably, the addition of a BTKi to chemoimmunotherapy lead to a mOS of more than 10 years in BTKi-naïve pts compared to 5.1 years in BTKi-exposed pts and 1.8 years in pts who did not receive a BTKi for RS treatment. Conclusions: Patients who develop RS often have high risk CLL, especially complex cytogenetics. Although a large proportion of pts with RS respond to frontline therapy, almost half relapse. While mOS is similar for anthracycline and platinum-based chemotherapies, platinum-based chemotherapy can lead to superior CR and PFS. BTKi-naïve pts who receive a BTKi with chemotherapy for RS treatment have superior mOS.
Real-world data of lebanese patients with chronic lymphocytic leukemia.
Authors: Nasr Lewis , Yehia Intissar , Diab Saada , Ghoche Ahmad , Nasr Fadi louis
Published: June 2022

e19512

Background: Many advances in the treatment of chronic lymphocytic leukemia (CLL) has been made in the 6 past years aiming at attaining durable complete responses and even cure. The choice of upfront therapy is driven by several factors including presence of 17p deletion or TP53 mutation, IGHV mutation status, patient fitness, comorbidities, drug availability and affordability etc.. The aim of the current study was to describe aspects of CLL in real world data setting in Lebanon regarding patients’ characteristics, diagnostic studies, indications for therapy and implication of new treatments including small molecule inhibitors including Bruton Tyrosine Kinase BTK and BCL2 inhibitors. Methods: This was an observational prospective study (2004-2021) of consecutively diagnosed patients with CLL at a single center in Lebanon. The characteristics, indication for treatment, types of treatment used were recorded progression free survival (PFS) was defined as the time from treatment initiation at first line until progression from any cause. Results: The registry covered 128 patients, 82 males and 46 females (ratio 1.78:1). Median age at diagnosis was 66 years. 23.6% were younger than 55 years. 73% of patients were asymptomatic at diagnosis, and 25% had lymphadenopathies. RAI stage 0 (BINET stage A) was observed in 73%. Median absolute lymphocytic count was 15,340 (unit), median hemoglobin was13.2. and median platelet count was 188,000. FISH panel was done in 56 patients (43%) and IGHV in 13%. 17p deletion was detected in 14.3%, and 13q deletion as a sole abnormality in 46.6%. 15.7% of patients required treatment at diagnosis; 52.6 % of them due to anemia/thrombocytopenia, and 15.8% due to presence of constitutional symptoms; other treatment indications included massive splenomegaly, and massive or symptomatic lymphadenopathy. 71 patients (55.4%) fell into the watch and wait category; 37 of which required treatment at some point during follow up with a median duration from diagnosis till starting treatment of 34 months.FCR Fludarabine + cyclophosphamide + rituximab (38.5%), BR bendamustine + Rituximab (23%), and Ibrutinib (19.2%) were the most common regimens used upfront. PFS was not reached. and correlation between genetic features and survival couldn’t be done, due to the relatively small number of patients whom showed progression. Conclusions: Epidemiologic characteristics of Lebanese patients with CLL is comparable to the international data.Molecular studies are being more implicated in the diagnostic workup. FCR and BR were mostly used upfront during the previous decade. We noticed a trend toward using Ibrutinib after 2016 in frontline and relapsed setting (after its approval and availability).
Population-wide patterns of care in chronic lymphocytic leukemia in Australia: An analysis of the pharmaceutical benefits scheme dataset.
Authors: Chuen Li Shu , Zhao Fei-Li , Gauba Raj , Yang Keri , Azmi Soraya , Tam Constantine Si Lun
Published: June 2022

e19518

Background: The treatment landscape in patients with chronic lymphocytic leukemia (CLL) is changing with the approvals of Bruton’s tyrosine kinase inhibitors (BTKis) in Australia. We sought to understand the practice impact of the introduction of publicly funded novel agents for the treatment of CLL. The objective of this study was to describe the evolving treatment patterns of Australian patients with CLL over the last 10 years using population-wide prescription records. Methods: Patients who initiated a treatment for CLL between 01/01/2011 and 07/31/2021 were extracted from the Services Australia 10% Pharmaceuticals Benefits Scheme (PBS) dataset. This dataset includes the dispensing records for 10% of the Australian population and captures all publicly funded treatments in Australia. The index date was defined as the commencement of any drug for the treatment of CLL. First-line (1L) therapy was defined as the first treatments prescribed for CLL. A patient was defined as relapsed/refractory (R/R) if they had commenced a drug which was in a different therapeutic category, or if they re-started the same regimen after a gap of more than 180 days. Descriptive analyses were conducted to examine the use of treatment regimens for the overall 10-year population by line of therapy. Analyses by calendar year were also performed to assess changes in treatment patterns. Results: Overall, 803 patients with CLL were identified. The majority of patients were male (65%) and age > 60 years (77%), with most being aged 70-79 years (33% of total). Many patients were receiving comedications at baseline, including antihypertensives (47%), antipsychotics or antidepressants (17%), and/or anticoagulants (13%). In the overall population (2011-2021), the majority of patients had received 1L treatment with fludarabine-cyclophosphamide-rituximab (FCR, 49%), chlorambucil ± CD20 (27%), or CD20 monotherapy (17%). The most commonly used regimens in R/R patients at any subsequent episode of treatment included CD20 monotherapy (56%), BTKi (41%) or FCR (33%). A trend in adoption of novel agents was observed throughout the years following their PBS listing. Analysis by calendar year showed that from 2011 to 2020 use of FCR in 1L decreased from 78% to 10%; and use of BTKis in R/R increased from 0% to 62%. Conclusions: CLL treatment patterns have significantly changed in Australia since the introduction of the BTKis (e.g., ibrutinib, acalabrutinib). The use of FCR in 1L CLL has decreased and use of BTKis in R/R patients has increased.
Incidence, predictors and outcomes of cardiovascular events in patients with chronic lymphocytic leukemia.
Authors: Ghous Ghulam , Gvazava Nanuli , Egwom Peter , Saleh Mohammad , Franco Diana , Shoukat Hafiz Muhammad Hassan , Au Pak Ho , Nwabara Kelechi , Tarar Zahid
Published: June 2022

e19524

Background: CLL accounts for about one-quarter of the new cases of leukemia and affects mainly elderly population. Recent literature highlights increased cardiovascular events in patients with CLL, notably those being treated with targeted therapy such as Bruton tyrosine kinase inhibitors. Here we examine data obtained from the National Inpatient Sample to find out incidence, predictors and outcomes of cardiovascular events in patients with CLL. Methods: We analyzed the National inpatient database from year 2019 and extracted the data of all patients with CLL. Multivariate regression analysis was performed to determine the aforementioned outcomes in CLL patients. Results: CLL patients showed increased odds of all cause in-hospital mortality (Adjusted Odds ratio (AOR) 1.28, 95% CI 1.19-1.38, P<0.001) in comparison to general adult population. CLL patients had higher odds of developing Atrial fibrillation (AOR 1.11, 95% CI 1.06-1.15 P <0.001) compared to patients without CLL. CLL patients had significantly higher odds of cardiac tamponade and pericardial effusion (AOR 1.64, 95% CI 1.10-2.42, P<0.001, 1.65 95% CI 1.43-1.92, P<0.001) respectively. Odds of congestive heart failure (AOR 0.97, 95% CI 0.93-1.01, P0.10) and atrial flutter (AOR 1.03, 95% CI 0.93-1.17, P 0.55) were similar between CLL patients and general adult populations. Patients with CLL have Increased mean hospital length of stay (adjusted mean LOS 0.51, 95% CI 0.42-0.61, p<0.001) and mean total hospital charges (adjusted mean charges 2006$, 95% CI 173$-3840$, P 0.03). [Table] We investigated the predictors of inpatient mortality in CLL patients and found that increase in age, black race, acute kidney injury, alcohol use, malnutrition and weekend admissions were associated with higher odds of mortality, whereas smoking, obesity, and female gender showed lower odds of mortality. Conclusions: CLL patients are at increased risk of developing atrial fibrillation, pericardial effusion, pericardial tamponade and all-cause in hospital mortality compared to their non-CLL counterparts, even after accounting for variables such as age, gender etc. Moreover, CLL patients have higher inpatient mortality associated with certain factors such as age progression, AKI, black race, alcohol abuse and malnutrition. Patients should be referred to cardiologist early and cardiovascular status should be optimized especially before initiating targeted therapy.[Table: see text]
COVID-19 pandemic experience in patients with Hodgkin lymphoma.
Authors: Prischak Sara E. , Ballard Hatcher J. , Duca Adam N. , Gerson James M. , Landsburg Daniel J , Barta Stefan K. , Svoboda Jakub
Published: June 2022

e19534

Background: Patients (pts) with Hodgkin lymphoma (HL) may be at an increased risk from COVID-19-related complications due to immunosuppression and common therapies with pulmonary toxicities (e.g. bleomycin, radiation). Additionally, they may experience unexpected adverse events (AEs) from the novel SARS-CoV-2 vaccines due to the intrinsic abnormalities in cellular immunity. Exploring their perspective on the COVID-19 pandemic and subjective AEs from the novel vaccines may ultimately allow providers to develop improved services based on needs of this specific population. Methods: We conducted a single-institution, questionnaire-based study in pts treated after 1/1/2015, for diagnosis of HL. Pts were identified through the electronic medical records at our institution. After signing an informed consent, pts answered 19 questions designed to reflect on their COVID-19 pandemic experience. An additional section aimed to determine the percentage of pts with a local or systemic AEs within 7 days of novel SARS-CoV-2 vaccine dose. Results: We enrolled 30 pts with median age 28.5 years (18-66); 16 (53%) were male, and 26 (87%) were on active HL therapy. With data cutoff 1/28/2022, 27 pts (90%) completed the questionnaire. A total of 8 (27%) patients had COVID-19 infection with 75% of those occurring after the vaccination. None required hospitalization and none reported residual pulmonary issues. Eighteen (67%) had a member of their household test positive for COVID-19. Most pts (67%) did not require cancellation of their appointments due to COVID-19-related issues during the pandemic. 85% of pts participated in at least 1 telehealth medical appointment and the majority (72%) were satisfied with their telehealth experience for cancer care. A total of 24 (80%) pts received the novel SARS-CoV-2 vaccines (58% had Pfizer-BioNTech BNT162b2, 38% Moderna mRNA-1273, 4% Ad26.COV2.S) and 23 pts completed the AE section of the questionnaire. The vaccines were generally well-tolerated. Six pts (26%) reported at least one grade 3 AE, but none had grade 4 local or systemic AEs. The most common AE was pain at injection site (65% after dose 1, 55% after dose 2, 69% after dose 3). AEs that occurred in over 25% of pts during any of the injections included redness/swelling/pain at the injection site, fatigue, headache, muscle pain, and fever. Of 23 eligible pts, 13 (57%) received 3rd dose of the vaccine. No unexpected toxicities or autoimmune issues were noted by participants in this study following vaccination with a median follow up of 10 months after the 1st vaccine dose. Conclusions: Based on responses from our study, HL pts adjusted to the challenges of the COVID-19 pandemic with minimal disruptions to their cancer care, showed positive attitudes toward telehealth, and appear without any unexpected toxicities from the novel vaccines.
Epidemiological characteristics and cause-specific survival analysis of plasmablastic lymphoma (PBL) using the SEER database.
Authors: Gor Dhairya , Gwalani Pranav , Gor Rajvi , Wiseman Kyle , Levitt Michael J. , Sen Shuvendu
Published: June 2022

e19546

Background: Plasmablastic lymphoma (PBL), a variant of diffuse large B-cell lymphoma, is a rare and aggressive malignancy. Minimal guidelines exist for its diagnosis and standard of care. Hence, we studied the epidemiological characteristics and survival variables of PBL patients by using the SEER 20 database. Methods: A total of 229 cases of PBL (WHO ICD-O-3 codes 9735/3) were identified between 2000 and 2015, after excluding 66 cases with unknown survival time or no microscopic confirmation. The epidemiological characteristics and the survival variables included were age, gender, ethnicity, Ann Arbor stage, B-symptoms, and site. The overall 5-year survival (OS), cause-specific 5-year survival (CSS), and cause-specific survival plots across different strata were plotted using the Kaplan Meier Method. The analysis was done using the Cox proportional hazard regression model (p < 0.05). Results: The incidence of PBL was 0.03 per 100,000 cases. It was more common in adults less than 60 years (61.57%), males (79.04%), and White ethnicity (72.49 %). There were more cases of patients with advanced Ann Arbor stages (3 or 4) PBL (52.84%), although some patients (5.68%) had unknown staging. There were 55.02% of extranodal cases, and 28.38% of patients had B-symptoms. The OS was 36.55%, and the CSS was 46.5%. CSS did not differ significantly based on age, race, or gender. However, the absence of B-symptoms was associated with better CSS (HR: 0.654, 95% CI: 0.455-0.941, p: 0.022). Nodal involvement (HR: 1.553, 95% CI: 1.135-2.124, p: 0.006) and advanced stages 3 or 4 (HR: 1.414, 95% CI: 1.018-1.962, p: 0.038) were also linked to a poor CSS. Conclusions: PBL patients with a primary nodal involvement and advanced staging (3 or 4) had poor CSS, and the absence of B-symptoms was associated with a better outcome. Age, gender, and ethnicity had no discernible effects on survival. We did not include therapeutic options in our study, and hence, further studies analyzing the impact of treatment options on PBL survival can be conducted.[Table: see text]
Outcomes and prognostic assessment of post-transplant lymphoproliferative disorder.
Authors: Shaikh Hira , Omer Zulfa , Jandarov Roman , Delman Aaron , Latif Tahir
Published: June 2022

e19548

Background: Post-transplant lymphoproliferative disorder (PTLD) is the most common malignancy after solid organ transplantation (SOT) in adults, apart from skin cancer. It is a serious and potentially fatal complication of chronic immunosuppression in SOT recipients. Methods: Institutional electronic health record (EHR), Epic was queried for PTLD patients evaluated at the University of Cincinnati Cancer Center 1991 - 2020. Relationships between clinical characteristics and time from diagnosis to death were assessed using t-test and ANOVA, with SAS 9.4. Overall survival (OS) was evaluated by Kaplan Meier estimates, from the date of PTLD diagnosis to death or last follow-up. Results: Sixty patients were identified with PTLD in the study period. A higher proportion of males (65%) and Caucasians (92%) was noted. The most common type of transplants were kidney (40%) and liver (32%). The median time from transplant to PTLD was 7.3 y and the median age at diagnosis was 54.5 y. The majority had monomorphic PTLD (60%) and presented as Stage IV (25%) or with end-organ dysfunction (67%). Most had extranodal involvement (67%), with GI (23%) being the most frequently involved site. EBV was positive in 32%. Immunosuppression was changed in 75% of the patients and most received rituximab-chemotherapy (55%), with two-thirds achieving a response. The 2-year OS was 55%. Gender (males 44%, females 14%; p = 0.0216), transplant type (lung 67%, liver 53%, kidney 21%, kidney-pancreas 0%; p = 0.0183) and treatment response (CR 20%, PR 29%, no response 100%; p = 0.0003) were significantly associated with mortality. Median time from PTLD diagnosis to death was 5.2 mo, being significantly shorter in liver transplant recipients (p < 0.0001), those managed by observation only (p < 0.0001) or with end-organ dysfunction at diagnosis (0.0072). A similar trend was noted in males, non-Caucasians, HLA-mismatch, and polymorphic PTLD, but this was statistically nonsignificant. Conclusions: This investigation highlights the prognostic risk factors of PTLD, that could be helpful in the management of the patients and guiding future research.[Table: see text]
Long-term survival projections of loncastuximab tesirine-treated patients in relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL).
Authors: Hamadani Mehdi , Graham Christopher N. , Liao Laura , Zhang Katherine H , Strat Hannah , Ungar David , Ai Weiyun Z. , Chen Lei , Carlo-Stella Carmelo
Published: June 2022

e19551

Background: Loncastuximab tesirine (loncastuximab tesirine-lpyl; Lonca) is an FDA approved CD19-directed antibody-drug conjugate for R/R DLBCL. From the LOTIS-2 trial primary data cut (April 6, 2020), overall response rate was 48.3% and median overall survival (OS) was 9.9 months. The OS Kaplan-Meier (KM) plot displayed a survival plateau suggesting the presence of long-term survivors (LTS). Survival analyses were conducted on a more mature data cut (March 1, 2021; median follow-up = 1.7 years, follow-up completeness at median = 81%) to estimate the percentage of LTS and expected lifetime survival (mean OS) for lonca-treated patients. Methods: Consistent with studies of other R/R DLBCL treatments, identified through a literature review, parametric and mixture cure models were fit utilizing multiple distributions. Flexible cubic spline (hazard scale 1-3 knots) and non-mixture cure analyses were also conducted. Age- and gender-matched United States life table hazards were used in projections for LTS and to ensure modeled hazards were not less than the general population. Best-fit models were determined through fit statistics, KM and fitted curve overlays, and clinical plausibility. The best-fit model from each method was a candidate for overall best fit. A hybrid model following the best-fit parametric/spline model to a defined time point and switching to general population mortality was also constructed. Results: Mixture and non-mixture cure models fit best (individual best fits gamma and Weibull, respectively). Parametric and spline models (individual best fits log-normal and 2 knot models, respectively) did not fit the observed data well nor fit the clinical expectation of long-term survival. Due to better fit, spline models were used in the hybrid model. LTS from the mixture cure and non-mixture cure models were 24-26%. Mixture cure, non-mixture cure, and hybrid model with a 2-year switch point were consistent in survival predictions (6.11-6.23 years). In a sensitivity analysis with 3-year switch point in the hybrid model, the estimated survival was shorter due to the switch point being below the observed survival plateau. Table presents full survival results and fit statistics. Conclusions: The observed survival plateau suggests lonca-treated patients may include LTS. Mixture cure, non-mixture cure, and hybrid models fit the trial data well and align on survival projections (6.11-6.23 years). Additional follow-up may help refine the switch point of the hybrid model and confirm presence of LTS.[Table: see text]
Use of circulating tumor DNA in newly diagnosed DLBCL patients.
Authors: Tomassetti Sarah , Samara Yazeed , LaBarbera Katie , Qing Xin , Rathore Richa , Aleshin Alexey , McPhaul Laron
Published: June 2022

e19552

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma. With upfront treatment, 40% of patients relapse. Currently, treatment response and surveillance are monitored using positron emission tomography/computerized tomography (PET/CT). However, no study to date has shown significant improvement in outcomes in lymphoma patients using standard radiographic and clinical surveillance. Most often, relapses likely occur from minimal residual disease (MRD) below the detection of imaging. Thus, a subclinical biomarker to better monitor treatment response and surveillance is needed. Circulating tumor DNA (ctDNA) has emerged as a sensitive biomarker for detecting MRD. Here, we aimed to evaluate the utility of ctDNA as a biomarker for monitoring treatment response and surveillance in patients with lymphoma. Methods: ctDNA analysis using a personalized, tumor-informed assay (Signatera bespoke mPCR NGS assay) was performed on blood samples collected from 15 patients with newly diagnosed DLBCL who presented to Harbor-UCLA Medical Center in 2021. Blood samples were collected at diagnosis, prior to each cycle of therapy, and every 3 months thereafter for surveillance. The primary endpoint was the rate of ctDNA clearance during treatment and its correlation with radiological imaging. Secondary endpoints included ctDNA positivity rate during surveillance and its correlation with radiological imaging. Additional data collected included patient demographics, lymphoma characteristics, and treatment regimen. Results: Of the 15 patients included in this cohort, the median age was 54 years and the percentage of patients with stage 1, 2, 3, and 4 disease was 7%, 20%, 7% and 67%, respectively. A total of 7% had high risk IPI scores. Within this cohort, 80% received RCHOP and 20% received daREPOCH. ctDNA was detected in 93.3% (14/15) of patients at diagnosis, with levels ranging from 2-3,607 mean tumor molecules (MTM)/mL of plasm. Of the ctDNA+ patients, 6 (40%) patients had a complete response to initial therapy as assessed by post-treatment imaging. Longitudinal assessment of ctDNA after each cycle of therapy revealed concordance with radiological findings, where 2/6 cleared ctDNA after cycle 1, 4/6 cleared ctDNA after cycle 2, 5/6 cleared ctDNA after cycle 3, and 6/6 cleared ctDNA after cycle 4 of treatment. One patient had undetectable ctDNA after cycle 4, but had a Deauville score of 4 on post-treatment PET/CT and was referred to radiation. Of the 3 patients who remained ctDNA positive on longitudinal testing, all were confirmed to have primary refractory disease by imaging. Of the remaining patients, 1 patient died after daREPOCH cycle 1 and 3 patients are undergoing initial therapy. Conclusions: ctDNA may serve as an important biomarker to assess response to treatment and for surveillance in DLBCL patients. Further studies evaluating ctDNA use in the clinical setting are needed before its application in routine practice.
Pharmacokinetics (PK) and pharmacodynamics (PD) in First-MIND: A phase Ib, open-label, randomized study of tafasitamab (tafa) ± lenalidomide (LEN) in addition to R-CHOP in patients (pts) with newly diagnosed diffuse large B-cell lymphoma (DLBCL).
Authors: Belada David , Kopeckova Katerina , Bergua Burgues Juan Miguel , Stevens Don A. , Nowakowski Grzegorz S. , Waldron-Lynch Maeve , Hadar Nira , Weirather Johannes , Lässig Charlotte , Blair Derek , Dreyling Martin H.
Published: June 2022

e19553

Background: The combination of tafa + LEN has accelerated approval in the United States (2020) and conditional approval in Canada and Europe (2021) for R/R DLBCL in ASCT-ineligible adult pts. A tolerable safety profile for R-CHOP + tafa ± LEN in pts with newly diagnosed DLBCL in the Phase Ib First-MIND study (NCT04134936) was previously reported, with numerically superior efficacy for R-CHOP + tafa + LEN (ASH 2021; #3556). We report PK, PD, and immunogenicity of R-CHOP + tafa ± LEN in this first line setting. Methods: Eligible pts ≥18 years with treatment-naïve DLBCL, IPI 2–5, and ECOG PS 0–2 were randomized 1:1 to either six 21-day (D) cycles (C) of R-CHOP (R-CHO, D1; P, D1–5) + tafa (12 mg/kg IV, D1, 8, 15) (Arm A) or R-CHOP + tafa + LEN (25 mg orally, D1–10) (Arm B). Secondary endpoints included tafa serum conc and number and percentage of pts developing anti-tafa Abs. Exploratory endpoints included natural killer (NK) cell, T-cell, and B-cell count in peripheral blood. Results: Data cut-off: 13 March 2021 for safety analysis, incl. ≥1 month follow-up after EoT visit for all pts; 15 September 2021 for efficacy. Tafa serum conc reached steady state by C3 (geometric mean trough conc: Arm A, 186.40–216.55 µg/mL; Arm B, 171.77–201.54 µg/mL) and steadily declined after treatment completion. Anti-tafa Abs were detected in 1/65 (1.5%) pts. This pt showed pre-existing tafa Abs at baseline, which decreased during treatment. Median NK cell count decreased from baseline at C1D8 but was at baseline or higher levels by EoT visit (Arm A) and C1D15 (Arm B; Table). T-cell count decreased from baseline at C1D8 in both arms but was at baseline level or higher by C1D15 (Arm A) and EoT visit (Arm B). Median B-cell count decreased from baseline to 0 cells/μL (Arm A, C1D15; Arm B, C1D8); at 6-month follow-up after EoT visit, B-cell count had recovered to measurable levels in ̃50% of pts. Conclusions: Tafa serum conc reached and maintained a therapeutic dose level in this first-line regimen and declined in line with known tafa half-life (̃16 days) after treatment completion; tafa levels were comparable between the two treatment arms. No pt developed treatment-induced or treatment-boosted anti-tafa Abs. Median NK-cell, T-cell, and B-cell counts were comparable between treatment arms in all cycles. Clinical trial information: NCT04134936. [Table: see text]
Clinical laboratory mutation analysis performed on aggressive B cell non-Hodgkin lymphoma patient biopsies.
Authors: Landsburg Daniel J , Caponetti Gabriel C. , Bagg Adam , Schuster Stephen J. , Nasta Sunita , Gerson James M. , Frank Dale M. , Barta Stefan K. , Svoboda Jakub , Bhattacharyya Siddharth , Qualtieri Julianne N , Lim Megan S. , Chong Elise A. , Roth Jacquelyn , Priore Salvatore F. , Deihimi Safoora , Morrissette Jennifer J.
Published: June 2022

e19561

Background: Results from comprehensive genomic analysis performed on aggressive B cell non-Hodgkin lymphomas (aBNHL) patient (pt) biopsies (bx) have identified mutations (mut) which may be predictive of pt survival. However, results from mut analysis (MA) performed on aBNHL pt bx in clinical laboratories are not well-described. Methods: Bx diagnostic of non-Burkitt aBNHL obtained from 7/2015-2/2021 with MA performed in the Penn Center for Personalized Diagnostics clinical laboratory using 3 consecutive versions of lymphoma sequencing panels were retrospectively analyzed. Mut tested varied by panel. Mut detected with variant allele frequency (VAF) ≥10% were included. Results: MA was performed on 293 aBNHL pt bx with a successful assay for 270 (7.8% failure rate). Request for MA was made by interpreting hematopathologist 93% and treating clinician 7%. Median turnaround time (TAT) from receipt of bx to result report was 18 (range 8-53) days. Notable pt characteristics included prior/concurrent indolent lymphoma (IL) 31% and prior systemic therapy received for IL and/or aBNHL 38%. Notable bx characteristics included bx type paraffin-embedded tissue 85% and bone marrow 12%, histologic classification diffuse large B cell lymphoma 86% and high grade B cell lymphoma 13%, cell of origin (COO) by Hans algorithm non-germinal center B (non-GCB) 51% and GCB 44%, known double expressor lymphoma 30%, known MYC rearrangement 18%, known double hit lymphoma 9% and any mut detected with VAF ≥10% 82%. Number and percentage of mut occurring in ≥10% of bx (minimum tested bx for mut ≥92) with associated COO are listed in the table. Subset analysis of 147 bx obtained from pts with newly-diagnosed aBNHL (15% with previously-untreated IL) had similar bx characteristics to the entire population were analyzed for the presence of mut reported in poor-prognosis COO-associated classifications: Cluster 5 for non-GCB and Cluster 3 for GCB (PMID: 29713087), double-hit signature (DHITsig) for GCB (PMID: 30523716) and molecular high grade (MHG) for GCB (PMID: 30523719). For 77 non-GCB bx, 19% had Cluster 5 mut. For 59 GCB bx, 56% had at least one of Cluster 3, DHITsig or MHG mut. Conclusions: Clinical laboratory MA performed on nearly 300 aBNHL pt bx was highly successful with a short TAT and demonstrated recurrent gene mut associated with aBNHL development. In the subset of bx from previously-untreated pts, MA identified mut associated with poor-prognosis genetic subtypes of aBNHL.[Table: see text]
Real-world treatment patterns in patients with Sézary syndrome in the United States and the impact of Covid-19.
Authors: Zhao Yang , Tang Jackson , Zhou Huanxue , Takahashi Takeshi , Nomura Takanobu , Dennis Eslie , Akilov Oleg
Published: June 2022

e19578

Background: Sézary syndrome (SS) is an aggressive type of cutaneous T-cell lymphomas (CTCL). Due to its low prevalence, there are limited data on real-world treatment patterns of currently available SS therapies. Furthermore, recent approvals of new agents for patients with CTCL as well as COVID-19 likely impacted real-world treatment patterns. Objective: To examine real-world treatment patterns and the impact of COVID-19 among SS patients treated in 2018-2020 in the US. Methods: Patients with public or private insurance in the 2018-2020 Symphony Health Solutions database were classified into 3 groups: ≥1 diagnosis of SS (ICD-10-CM code: C84.1x) in 2018, 2019, and 2020, respectively. Patient characteristics and treatment patterns for all therapies recommended by the National Comprehensive Cancer Network guidelines version 2.2021 were examined: systemic therapy (e.g., extracorporeal photopheresis (ECP), parenteral, or oral agents), skin-directed therapy (SDT, e.g., topical, local radiation, total skin electron beam therapy, or phototherapy) and bone marrow transplant. The impact of COVID-19 was assessed via quarterly analysis. National drug codes, current procedural terminology and healthcare common procedure coding system codes were used to identify all treatments. Results: The analyses included 869, 882, and 853 SS patients in 2018, 2019, and 2020, respectively (mean age: 66.3, 66.9 and 67.3 years; male: 54.4%, 54.8%, and 55.6%). Overall, systemic therapy increased from 2018 to 2020 (41.8% to 46.5%), with increased parenteral (20.7% to 28.7%) but decreased ECP (17.0% to 13.5%) usage. SDT increased from 2018 to 2020 (48.9% to 52.9%), with increased topical (42.3% to 48.3%) but decreased phototherapy (6.3% to 4.1%) usage. ECP, mogamulizumab, and bexarotene were the most prescribed systemic therapies in 2019-2020, with mogamulizumab being the only one with increased usage over time. Quarterly analysis showed a decreasing ECP from Q1 to Q4 within each year, with a notable drop in Q2 2020. For parental systemics, there was an increasing trend in 2019 and 2020, but utilization in Q4 2020 was lower than that of Q3 2020. For oral systemic, there was a notable drop in Q2 2020 but an increased trend in Q3-Q4 2020. Conclusions: This claims analysis indicated increased use in systemic and SDT among SS patients in 2018-2020. The quarterly analysis indicated that the drop in ECP and oral systemic usage in Q2 2020 coincided with the onset of the pandemic, but there was a stable use of parenteral systemic during 2020.
Results from a phase 1b study of blinatumomab-pembrolizumab combination in adults with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL).
Authors: Giri Pratyush , Patil Sushrut , Ratnasingam Sumita , Prince H. Miles , Milliken Samuel , Briones Meijide Javier , Coyle Luke , Van Der Poel Marjolein , Mulroney Carolyn M. , Farooqui Mohammed Z. H. , Wong Hansen , Desai Rajendra , Zugmaier Gerhard , Mergen Noemi , Cannell Paul
Published: June 2022

e19584

Background: This open-label, multicenter, phase 1b study evaluated the safety and efficacy of blinatumomab and pembrolizumab combination therapy in patients (pts) with R/R DLBCL (NCT03340766). Methods: Key inclusion criteria included adults with ECOG performance status ≤2 and life expectancy ≥12 weeks. In cycle 1, pts received a continuous intravenous (cIV) infusion of blinatumomab followed by step dosing to the target dose (TD; Table). After a 28-day treatment-free interval, cIV infusion of blinatumomab was administered for 28 days in cycle 2 with the same dose escalations as in cycle 1. Pembrolizumab 200 mg IV was administered once every 21 days starting on day 15 in cohort 1a, and on day 19 in cohorts 2a and 3a. Pts were premedicated with dexamethasone. Dose-limiting toxicities (DLT) were the primary endpoint. The maximum tolerated dose (MTD) was the highest dose level at which ≤1 of 6 or ≤2 of 10 pts experienced a DLT. Results: As of June 10, 2021, 31 pts were enrolled in cohorts 1a, 2a, and 3a (Table). DLTs occurred in 1 (10%) pt in cohort 1a (neutropenia) and 2 (40%) pts in cohort 3a (cognitive impairment, and elevated AST, ALP, and GGT levels). Treatment-emergent (TE) adverse events (AEs) were observed in 31 (100%) pts; grade ≥3 AEs occurred in 29 (94%) pts. The most frequent grade ≥3 TEAE attributed to blinatumomab was nervous system disorders (11 [35%]) and that attributed to pembrolizumab was blood and lymphatic system disorders (5 [16%]). Serious blinatumomab-related and pembrolizumab-related AEs were observed in 15 (48%) and 2 (6%) pts, respectively. Fourteen (45%) deaths occurred; none were treatment-related. Cohort 2a dose was determined as the MTD (Table). In cohort 2a, the objective response rate within 12 weeks of blinatumomab treatment was 30%; the median duration of response in responders (n = 8) was 176.5 (range: 28–680) days. Exposures of blinatumomab and pembrolizumab in this combination study were consistent with historical data for the individual agents. Conclusions: The cohort 2a dosing schedule with TD of 56 μg/day of blinatumomab was established as the MTD. The study was terminated after dose finding because the MTD of blinatumomab in combination with pembrolizumab was lower than the MTD of blinatumomab monotherapy, with no apparent efficacy gain. Clinical trial information: NCT03340766. [Table: see text]