bluuebunny/crossref_metadata_2025 huggingface dataset:
Retrospective analysis of toxicities and clinical outcomes with BCR-ABL1 tyrosine kinase inhibitors in B-cell acute lymphoblastic leukemia.
Authors: Venn Chad Michael , Zacholski Kyle , Tran Valerie , Alnimer Yanal Mufeed , Ho Thuy , Maher Keri Renee , Bouligny Ian Michael
Published: June 2022

e19039

Background: The rapid adoption of BCR-ABL1 TKIs in Ph+ B-ALL occurred despite a lack of comparative trials, leading to an absence of data regarding the additive toxicities of BCR-ABL1 TKIs with many standard chemotherapy regimens. BCR-ABL1 TKIs have been associated with severe adverse events and may significantly impact treatment-related morbidity and mortality. The objective of this study is to describe the cumulative toxicity imposed by BCR-ABL1 TKIs and chemotherapy regimens. Methods: A total of 48 patients with Ph+ B-ALL treated with a BCR-ABL1 TKI plus chemotherapy between January 2015 and October 2021 were eligible to assess treatment-related toxicity. High-intensity chemotherapy regimens included HyperCVAD, CALGB 10403, ECOG1910, and ECOG2993; low to moderate intensity regimens included EWALL-Ph-01, TKI + POMP, TKI + corticosteroids, and TKI monotherapy. Regimens containing blinatumomab and inotuzumab ozogamicin in combination with a TKI were assessed separately. The primary outcome was the occurrence of grade 3/4 toxicities, as defined by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The first occurrence of CTCAE toxicities was collected for each line of therapy patients received. Results: Among the 48 patients analyzed, 71 total lines of therapy were identified. Of these, 54.9% (n = 39) were classified as high-intensity, 29.6% (n = 21) were low-moderate intensity, 9.9% (n = 7) were blinatumomab, and 5.6% (n = 4) were inotuzumab ozogamicin. In high- and low-moderate intensity regimens, a mean of 10.1 and 6.9 grade 3/4 toxicities occurred with dasatinib and imatinib, respectively (p = 0.076). Among low-moderate intensity regimens with dasatinib (n = 11), 63.6% (n = 7) discontinued dasatinib, 9.1% (n = 1) decreased the dasatinib dose, and 36.4% (n = 4) decreased or discontinued dasatinib due to toxicity. High-intensity chemotherapy regimens with dasatinib demonstrated 51.6% (n = 16) discontinuation, 38.7% (n = 12) dasatinib dose reduction, and 62.1% (n = 18) decreased or discontinued dasatinib due to toxicity. Conversely, among low-moderate (n = 4) and high-intensity (n = 5) regimens in combination with imatinib, no discontinuations or dose reductions occurred. These data demonstrate a greater dose reduction and discontinuation rate with dasatinib compared to imatinib in high-intensity regimens (p = 0.011); differences in low-moderate intensity regimens were not observed (p = 0.174). A secondary analysis did not reveal an association with dasatinib discontinuation rate and CR rate (p = 0.829) or overall survival (p = 0.941). Conclusions: A greater incidence of grade 3/4 toxicity leading to dose changes or discontinuation occurred with dasatinib compared to imatinib. While differences in CR or OS due to TKI-related toxicity were not identified, their occurrence likely contributes to treatment-related morbidity.
Mucormycosis in hematopoetic stem cell transplant recipients: A systematic review.
Authors: Rehman Mohammad Ebad Ur , Saeed Sajeel , Franco Diana , Chattaraj Asmi , Basit Jawad , Khan Hamza , Fazal Faizan , Anwer Faiz
Published: June 2022

e19043

Background: Mucormycosis is a life-threatening infection caused by opportunistic fungi belonging to the order Mucorales. High mortality is reported in hematopoietic stem cell transplant (HSCT) recipients who develop mucormycosis in the post-transplant immunosuppressed state. This study reviews the epidemiology, diagnosis, treatment and outcome of mucormycosis in HSCT recipients. Methods: A systematic literature search was conducted on PubMed and Embase from inception to 5 Jan, 2022 using MeSH terms for 'mucormycosis' and 'hematopoietic stem cell transplantation'. We included case reports, case series and observational studies reporting individual patient data. Summary statistics were calculated for patient characteristics by tabulation and percentages. Hazard ratios were calculated using unconditional Cox proportional hazard models. Data analysis was done using SPSS. Results: The initial search revealed 405 articles. After exclusion of duplicates, reviews and non-relevant articles, data was included from 122 articles (183 patients). The most common sites of infection were lung (36.6%) and rhinocerebrum (7.1%). Disseminated infection occurred in 34 (18.6%) cases. Diagnosis was confirmed using histology, culture or both in 27%, 13% and 34% of cases, respectively. Seven genera of zygomycetes were identified, of which Rhizopus was most common (37.2%). The most common antifungals used were liposomal amphotericin B (LAMB) (74%) and posaconazole (27%). Surgical debridement was employed in 64 (35%) cases. Overall survival was 32% with LAMB and 34% with surgical debridement. Sixteen patients did not receive any therapy; none survived. Mortality was reported in 121 patients (68.4%). Death was attributed to mucormycosis in 84 cases (45.9%). Death attributed to mucormycosis was more frequent in Rhizopus infections (56%) compared to other species (40%, HR = 1.89, 95% CI 1.13-3.15, p < 0.05). Patients who underwent HSCT due to chronic myeloid leukemia (CML) had greater mortality due to mucormycosis (72%) compared to those with other underlying diseases (43%, HR = 2.31, 95% CI 1.26-4.21, p < 0.05). Conclusions: Mucormycosis has high mortality in HSCT recipients. Surgery and LAMB therapy can significantly improve survival. Prospective studies need to be undertaken to identify risk factors for mortality and appropriate treatment strategies. [Table: see text]
Initiation of an eligibility screening protocol prior to tissue typing of potential stem cell donors resulted in substantial cost savings.
Authors: St. John Luke , Gregory Tara K. , Wagner Patricia , Meissner Sarah , Schade Henning , Bearman Scott Irvin , Nash Richard A. , Rotta Marcello , Matous Jeffrey V. , Eghtedar Alireza , Tees Michael Timothy , Maris Michael B. , Mountjoy Luke
Published: June 2022

e19047

Background: Human Leukocyte Antigen (HLA) typing is a necessary but expensive process to identify suitable donors for allogeneic hematopoietic cell transplantation (HCT) for the treatment of bone marrow disorders and hematologic malignancies. The likelihood of a patient and sibling being fully HLA matched is 25%. An HLA-identical related donor remains the preferred source among HCT recipients due to superior outcomes when compared to unrelated, mismatched, haploidentical, or cord blood. Because of the high probability of finding an HLA matched donor among siblings, and the benefit of quick access to these donors, it had been standard procedure at our institute to test all siblings to identify potential matches. The estimated costs of HLA typing alone is approximately $300-$1000 and is contingent upon the lab utilized and resolution of typing. The costs of HLA typing, additional testing, and screening are significant to patients and health care systems. Methods: Our institution initiated a protocol to assess potential sibling donors prior to HLA typing as per the donor eligibility guidelines of the National Marrow Donor Program (NMDP). From 2018-2020 each sibling was given a questionnaire prior to HLA typing and screened for suitability. If a sibling was determined to be ineligible for donation based on the NMDP guidelines, HLA typing and work up for that sibling was not pursued. Results: Between 2018 and 2020 we identified 789 potential donors for HCT. All potential donors were sent eligibility questionnaires. Based on this screening, 568 potential donors were found to be eligible for donation whereas 221 were ineligible. HLA typing was pursued in all eligible donors. This resulted in and estimated cost savings of $66,000-$221,000 in HLA typing alone. This translated into a substantial health care cost savings for our institution as compared to our prior policy of typing all siblings. Conclusions: Identification and work up for potential HLA matched siblings is critical for identifying optimal donors for HCT. Our previous policy of universal sibling screening was found to be costly due to typing individuals who later were found to be ineligible to donate. We found that the initiation of a simple donor screening protocol that excluded ineligible sibling donors resulted in significant cost savings compared to our prior policy of HLA typing all potential sibling donors. Cost savings are a relevant consideration in all aspects of healthcare and this screening tool could be a practical component of the best practice guidelines for HLA matching and HCT.
The efficacy and safety of second allogeneic hematopoietic stem cell transplantation.
Authors: Toprak Selami Kocak , Kırcalı Ekin , Cengiz Seval Guldane , Civriz Bozdag Sinem , Yuksel Meltem Kurt , Topcuoglu Pervin , Arslan Onder , Ozcan Muhit , Demirer Taner , Gurman Gunhan , Beksac Meral , Ilhan Osman
Published: June 2022

e19048

Background: Second allogeneic hematopoietic cell transplant (sAHCT) might be indicated following a graft failure or disease relapse after the first one; although it might emerge with high rates of morbidities and mortality. Currently, there is a limited number of publications on this matter in the literature, here we aimed to share our sAHCT experience from a single center. Methods: Data from 51 patients who were eligible for sAHCT between 2001 and 2021 was evaluated retrospectively. All data was obtained from the Ankara University Faculty of Medicine, Department of Hematology and Bone Marrow Transplant Unit. Results: 51 patients were included in the present study. Median age at sAHCT was 34 (18- 65) and female/ male ratio 19/ 32 (37.3% / 62.7%). The same donor from the first transplant was eligible for sAHCT for most patients (n= 46, 90.2 %). sAHCT indication was graft failure for 11 patients (21.6 %) whereas 40 (78.4 %) patient went on sAHCT for disease relapse. Patients’ diagnoses were as follows: acute myeloid leukemia (n= 26, 50.9 %), acute lymphoblastic leukemia (n=9, 17.6 %), myelodysplastic syndrome (n= 6, 11.8 %), aplastic anemia (n= 6, 11.8 %) and others (CMML, CML, biphenotypic leukemia). Median number of transplanted CD34+ hematopoietic cells was 5.77 x x106/ kg (1.11- 8.29). Stem cell source was either bone marrow (n= 5, 9.8%) or peripheral blood (n= 46, 90.2 %). Myeloablative conditioning regimens were used for most sAHCTs (n= 30, 58.8%). Median overall survival (OS) rates for graft failure and disease relapse groups were 12.8 and 18.7 months, respectively (p= 0.63). During early transplant phase, 20 patients (39.2 %) died due to bone marrow aplasia, transplant failure or other complications. 1 year OS of the entire cohort was 33.3 % whereas 2-y- OS was 21.6% (95% CI= 25-45). 2 patients (3.9 %) died due to COVID19 during transplant process. On univariate analysis, sex, time from the first transplant (<12 months/ ≥12 months), conditioning intensity, sAHCT indication did not statistically significantly influence OS. Multivariate analysis confirmed a lower ECOG score (<2) at sAHCT significantly increased OS (p= 0.001). Conclusions: Based on this single center study, sAHCT is an efficacious treatment modality especially for patients with lower ECOG scores. sAHCT may offer long term survival for both graft failure and disease relapse states.
Treatment with anti-spike monoclonal antibodies in allogeneic HCT and CAR T-cell recipients with mild to moderate COVID-19: The Mayo Clinic experience.
Authors: Mohty Razan , Thoendel Matthew , Swei Samuel , Bansal Radhika , Palmer Jeanne , Hogan William J. , Vergidis Paschalis , Munoz Javier , Iqbal Madiha , Yassine Farah , Bennani Nabila Nora , Hathcock Matthew , Murthy Hemant S. , Castro Januario E. , Lin Yi , Razonable Raymund R. , Kharfan-Dabaja Mohamed
Published: June 2022

e19049

Background: Prognosis of COVID-19 is poor in the setting of immunosuppression. Casirivimab/imdevimab (REGEN-COV), bamlanivimab, and sotrovimab are investigational monoclonal antibodies (MoAbs) authorized for treatment of mild/moderate COVID-19 for patients (pts) 12 years or older and who are at high-risk for progression to severe COVID-19. These neutralizing antibodies, against SARS-CoV-2 spike proteins, have been shown to decrease risk of progression to severe disease. Recipients of allogeneic stem cell transplants (allo-SCT) or chimeric antigen T cell therapy (CAR T cell) represent a high risk population. However, treatment outcomes with these MoAbs in these pts are not well described. Methods: This retrospective study included 33 consecutive adult pts who developed mild/moderate COVID-19 and received anti-spike SARS-CoV-2 MoAbs between December 2020 and November 2021. Allo-SCT (N=27) or CAR T cell (N=6) recipients were included, and outcomes were analyzed separately. Pts received REGEN-COV (N=19), bamlanivimab (N=11), or sotrovimab (N=1), missing (N=2). Results: In the allo-SCT cohort (N=27), median age at time of COVID-19 was 55 (23-76) years. Median time from allo-SCT to COVID-19 was 31 (22-64) months. Two pts received CAR T-cell therapy prior to allo-SCT. Diagnoses included leukemia or myeloid diseases (82%), lymphoma (11%), or myeloma (7%). Transplant characteristics are summarized (Table). Thirteen pts were vaccinated against SARS-CoV-2 prior to breakthrough COVID-19. Events considered included hospitalization due to COVID-19, disease progression, or death from any cause. The 6-month event-free and overall survivals were 81% and 91%, respectively. In the CAR T cell recipients cohort (N=6), 4 pts received axicabtagene ciloleucel for diffuse large B-cell or follicular lymphoma and 2 received brexucabtagene autoleucel for mantle cell lymphoma. The median follow-up was 8 (1-11) months. Two pts received autologous SCT prior to COVID-19. Median time from CAR T cell therapy to COVID-19 was 10 (3-24) months. Three pts were vaccinated prior to COVID-19. Only 1 pt was hospitalized due to severe COVID-19 requiring mechanical ventilation leading to death. Conclusions: These results show a potential benefit of MoAbs in high-risk pts, namely allo-SCT or CAR T cell recipients. Future studies should evaluate the role of prophylactic use MoAbs in these populations. A comparative analysis with a matched control cohort (who did not receive MoAbs) will be provided at the meeting. [Table: see text]
Palliative care pilot initiative for transplant patients: The Westchester Medical Center experience.
Authors: Mowatt Kelley , Danyko Stephanie , Barrie Mariama-Seray , Gordon Sandra , Marcotte Kathy , Rotundo Erica , Schoenfarber Adam , Ahmed Tauseef , Liu Delong , Seiter Karen , Lugassy Mara , Steinberg Amir S.
Published: June 2022

e19050

Background: It is well known HCT recipients experience multiple symptoms affecting quality of life. Emerging data supports the role palliative care can play in mitigating these issues. Our cellular therapy team collaborated with the Palliative Care team on a pilot project incorporating their expertise into the management of our new allogeneic transplant patients. We chose this group of patients given their increased needs relative to other cellular therapy recipients (i.e. autologous, CTL) and our institution’s available resources. Methods: Patients admitted to the HCT unit for allogenic stem cell transplant underwent palliative care consult during their conditioning regimen. During the initial palliative care visit, performed by a specialist palliative care nurse practitioner, patients underwent comprehensive assessment of physical symptoms, psychosocial distress, and overall quality of life. Patients were then followed during hospitalization by members of the palliative care team including Nurse Practitioner, Social Worker and Chaplain, to address identified needs and support both the patient and their family. The palliative care team provided daily communication and recommendations to our inpatient HCT team. Results: Patient one was a 61-year-old man with intermediate risk MDS who underwent a reduced intensity conditioning regimen of busulfan, fludarabine, and alemtuzumab. His transplant was complicated by delirium and anorexia. Patient two was a 63-year-old man with AML who underwent a reduced conditioning regimen of the same combination. His transplant was complicated by bone pain and insomnia. Patient three was a 70-year-old woman with AML who also underwent a reduced conditioning regimen. Her transplant was complicated by severe mucositis and gastric reflux. Conclusions: Allogeneic stem cell transplant patients experience a multitude of symptoms and psychosocial distress. With the help of a dedicated palliative care assessment, we can improve patients’ quality of life during their admission for the transplant. Considering the positive feedback from patients, we plan to conduct a formal prospective study evaluating the impact of palliative care on adult stem cell transplant patients at our institution. By addressing the patient’s whole person rather than just their disease, we also hope to decrease number of admissions as well as length of stay. Ultimately, we look forward to expanding this to other malignancies as well.
Ruxolitinib in chronic steroid-refractory graft-versus-host-disease.
Authors: Kovalenko Iuliia , Saleem Tabinda , Laek Babray , Ali Rimsha , Mirza Taaha Muddassir , Chattaraj Asmi , Wahab Ahsan , Tamez ud din Asma , Qurashi Hafiz , Golubykh Konstantin , Malik Maidah , Khan Rafiullah
Published: June 2022

e19053

Background: Ruxolitinib, an elective Janus Kinase (JAK) 1/2 inhibitor, has been approved by FDA for the treatment of steroid-refractory chronic graft-versus-host-disease (SR cGVHD) after the failure of one or two lines of systemic therapy in adult and pediatric patients 12 years and older. However, it remains underutilized despite promising results in the treatment of SR cGVHD. Methods: We did a comprehensive literature search across various data sets, including PubMed, Cochrane, and Embase, and presented data in ASH and ASCO. A review of the most recent data is summarized in this abstract. Results: Two retrospective cohort studies and one pilot prospective study evaluated ruxolitinib in SR cGVHD. In a retrospective cohort study by Yang et al., 36 patients with SR cGVHD treated with ruxolitinib showed complete response (CR) in 27.8% of patients with complete disappearance of cGVHD symptoms and partial response (PR) with symptom relief of 52.7% at a dose of 2.5 to 10 mg two times daily with ruxolitinib tapering one week after symptoms improvement. In the pilot prospective study by Mozo et al., 12 pediatric patients with SR cGVHD received ruxolitinib at a dose of 2.5 to 10 mg two times daily and showed CR in 8.3% of patients and PR in 82.7% of patients. Morozova et al. conducted a prospective pilot study in 20 patients with primary or secondary myelofibrosis who were treated with pre-transplant ruxolitinib 45 mg/day from ruxolitinib (45 mg) starting from seven days before transplant to 2 days before the transplant, and 15 mg from day five after transplant to day 100 after transplant along with cyclophosphamide 50 mg/kg on days three and four after transplant. PR was observed in 47.1% of patients at 6 months with the incidence of cGVHD of 20%. In Phase III trial by Zeiser et al. reported CR of 6.7% and PR of 43% in 165 patients treated with ruxolitinib at a dose of 10 mg daily for 6 cycles (28 days/cycle). The most common all-grade adverse events are listed here. Conclusions: Ruxolitinib was recently approved by FDA for the treatment of SR GVHD and should be utilized more due to its high effectiveness and tolerable safety profile.[Table: see text]
Characteristics and clinical outcomes among patients receiving either ibrutinib or anti-CD20 monotherapy as first-line (1L) treatment for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): A retrospective analysis in community oncology practice.
Authors: Vose Julie , He Jinghua , Lu Xiaoxiao , Wu Linda , Ran Tao , Panjabi Sumeet
Published: June 2022

e19056

Background: Ibrutinib is an oral, once daily Bruton’s tyrosine kinase inhibitor and is a targeted treatment that has demonstrated progression-free survival and overall survival benefits in multiple phase 3 trials across age, fitness, and high-risk markers for CLL/SLL. Despite ibrutinib established as a preferred first-line (1L) treatment option, anti-CD20 monotherapy (rituximab or obinutuzumab) has been prescribed as symptomatic or palliative therapy. This retrospective study compared outcomes between ibrutinib and anti-CD20 monotherapy for CLL/SLL patients who initiated a 1L of therapy in community oncology practice. Methods: The nationwide Flatiron Health Electronic Health Record-derived de-identified database (03/04/2016-08/31/2021) was used to select patients with CLL/SLL who had ≥2 clinic visits and started 1L therapy with ibrutinib or anti-CD20 monotherapy. Patient baseline characteristics prior to 1L initiation were compared between the two treatment groups. Propensity score-based inverse probability of treatment weighting (IPTW) was used to adjust for baseline differences between treatment groups. Kaplan-Meier (KM) analysis was used to evaluate time to next treatment (TTNT) from 1L initiation. Two subgroup analyses were performed among patients with high-risk cytogenetic markers (deletion 17p or 11q, or unmutated IGHV) and those without IGHV testing. Results: Overall, 3,226 patients were included in the analysis, of whom 2,188 (67.8%) received ibrutinib and 1,038 (32.2%) received an anti-CD20 antibody. The average age was 71.4 years for ibrutinib patients and 72.9 years among anti-CD20 users. Patients treated with ibrutinib were more likely to have high-risk cytogenetic markers (42.6% vs 27.9%). Ibrutinib-treated patients overall had a significant 70% risk reduction of initiating a subsequent treatment compared with anti-CD20 group (Table). Similar results were also found in subgroups of patients with high-risk and those without IGHV testing. Conclusions: IPTW-adjusted analysis showed that in the real-world community practice setting, treatment with ibrutinib resulted in a statistically significantly lower risk of initiating subsequent treatment than the anti-CD20 group including patients with high cytogenetic risk features and without IGHV testing.[Table: see text]
Clinical outcomes and healthcare resource utilization (HCRU) in patients (pts) with lower-risk myelodysplastic syndromes (LR-MDS) reinitiating erythropoiesis-stimulating agents (ESAs) following previous ESA treatment.
Authors: Garcia-Manero Guillermo , Matsuno Rayna K. , McBride Ali , Brown Thomas D. , Idryo Danny , Broome Ronda , Herriman Autumn , Johnson Tiffany , Wilkinson Kristiana , Walters Sheetal , Schrag Andrew , Johanson Colden , Izano Monika A. , Mukherjee Sudipto
Published: June 2022

e19067

Background: The median survival for pts with LR-MDS is estimated to be 5–10 years. ESAs are utilized as first-line treatment for anemia in LR-MDS; however, real-world treatment patterns, clinical outcomes, and HCRU for pts with LR-MDS who reinitiated ESAs following previous discontinuation are not well-established. Methods: This was a retrospective study of pts with LR-MDS in a network of US community health systems who initiated ESAs as first-line therapy between January 1, 2016 and June 30, 2019 and were followed through June 30, 2021. Pts were required to have discontinued (had a ≥ 3-week gap between treatment with epoetin alfa, or a ≥ 6-week gap between treatment with darbepoetin alfa) and subsequently reinitiated ESA therapy at least once during follow-up. Outcomes included failure to achieve transfusion independence (TI), progression to acute myeloid leukemia (AML), overall survival (OS), number and type of health system visits, and medication use. TI was defined per IWG 2006 criteria in the subset of pts who had received ≥ 1 transfusion in the 8 weeks prior to ESA initiation. Results: There were 108 pts with confirmed LR-MDS who initiated ESA-based therapy. Pts had a median age of 79 years at diagnosis (interquartile range [IQR] 73–85), were predominantly male (58%), White (97%), and overweight or obese (52%). The median follow-up period was 17.0 months (IQR 7.2–34.7). The most used ESA was darbepoetin alfa (60%), followed by epoetin alfa (38%) and epoetin alfa-epbx (2%). Of the 33 pts who received a baseline transfusion, 52% did not achieve TI; 53% and 43% failed to achieve TI at 6 and 12 months, respectively. The majority of pts were repeatedly treated with ESAs (n = 61, 56%). Among these patients, 2% progressed to AML and 48% died during follow-up; median OS was 45 months. The median number of health system visits per patient-month was 3.2 (IQR 0.6–4.9); 89%, 62%, and 72% of pts had ≥ 1 outpatient, emergency department, or inpatient visit respectively, with median length of hospitalization of 12 days (IQR 4.8–27.8). Most pts (54%) received an antibiotic at least once during follow-up; overall, use of immunosuppressive therapy (2%) or iron chelation (3%) was rare. Conclusions: In this real-world study of community practice in the USA, reinitiation of ESA treatment after prior discontinuation in LR-MDS was prevalent. In these pts, poor clinical outcomes and frequent health system visits were observed. This study highlights the need to consider alternative treatment options for pts with LR-MDS.
Impact of imbalanced gender participation in online myeloproliferative neoplasm symptom surveys.
Authors: Langlais Blake , Mazza Gina L. , Scherber Robyn Marie , Geyer Holly , Gowin Krisstina L. , Palmer Jeanne , Kosiorek Heidi E. , Mead-Harvey Carolyn , Butterfield Richard , Mesa Ruben A. , Dueck Amylou C.
Published: June 2022

e19078

Background: Patients with myeloproliferative neoplasms (MPN), including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF), experience chronic disease-related symptoms. Surveying these patients while incorporating the MPN-Symptom Assessment Form (SAF) gains valuable insight. Independent surveys evaluating symptoms among MPN patients have seen disproportionate participation among females compared to males (upwards of 4:1). Though the general MPN patient population is roughly gender balanced, epidemiological studies show the occurrence of MPN types differ between men and women (MPN [%male]: PV [65%], ET [33%], MF [50%]. Mehta, et al. Leuk & Lymph 2014). In-clinic evaluations and international MPN surveys of disease-related symptoms suggest women report higher symptom burden on average compared to men, despite MPN type [Emanuel, et al. JCO 2012. Geyer, et al. Haematol 2017]. Further, a recent study across cancer trials showed women had a 34% increased risk of reporting severe symptoms [Unger, et al. JCO 2022]. This study aimed to evaluate gender imbalance in survey participation among MPN patient surveys and investigate its potential to overestimate symptom burden if gender is ignored. Methods: Five anonymous web-based surveys were used to assess the impact of disproportionate gender participation. The MPN-10 assessing the 10 most clinically meaningful SAF items was present in these surveys and generated the Total Symptom Score (TSS). Survey responses with no self-reported gender or ≥5 missing MPN-10 symptoms were excluded. Raking weights based on expected MPN population were applied at the survey- and MPN type-level. Relative bias of mean TSS was calculated to evaluate over- and underestimation due to this participation imbalance. Relative bias <5% is commonly acceptable. Results: There were 4962 survey participants total and 74% were female (Table). Epidemiologically expected gender frequency by MPN type was not seen (MPN [%male]: PV [31%], ET [15%], MF [37%]). The gender participation imbalance accounted for a 3.1% overestimation of overall TSS. This also resulted in a 6.8% underestimation of the mean difference in TSS between genders, across MPNs. Conclusions: Overall bias due to gender participation imbalance was relatively low. However, analyses considering gender differences were more impacted. Anonymous surveys should seek to reduce participation bias during the survey design phase. More research is needed to evaluate gender and other participation biases in surveys across cancer domains.[Table: see text]
Risk of second primary malignancy in patients with primary myelofibrosis: A SEER database study.
Authors: Joshi Utsav , Bhattarai Adheesh , Gaire Suman , Gill Simrat , Agrawal Vishakha , Bhetuwal Uttam , Kouides Peter , Bhatt Vijaya Raj
Published: June 2022

e19079

Background: Primary myelofibrosis (PMF) carries a poorer prognosis compared to other BCR-ABL-negative myeloproliferative diseases (MPD), and there is increased risk of early mortality due to blast transformation, thrombosis, bleeding complications, and progression of disease. Prior studies report greater incidence of second primary malignancy (SPM) among MPD patients, although the true risk in PMF has not been elucidated. We performed a large database study to evaluate the risk of SPM in PMF patients and analyzed the effects of sociodemographic factors on the risk of SPM. Methods: We used the Surveillance, Epidemiology, and End Results (SEER) database to identify all patients with a histologic diagnosis of PMF from 2009 to 2018. SPM was defined as any subsequent malignancy that developed at least 1 year after the diagnosis of PMF. Using multiple primary standardized incidence ratio (SIR) session of the SEER*Stat software (version 8.3.9), we calculated SIR and absolute excess risk (AER) of SPM for the entire cohort of PMF and also stratified based on age, sex, race, marital status, receipt of chemotherapy, follow-up duration, and year of diagnosis. We generated the 95% confidence intervals (CI) and p-values assuming Poisson distribution of the observed incidences of SPM. Results: A total of 5,273 patients with PMF were included in the analysis, of which 342 patients (6.4%) developed SPM. SPM occurred at SIR of 1.97 (95% CI 1.77-2.18, p<0.05) and AER of 151.87 per 10,000 population. A significantly higher incidence of melanoma (SIR 1.96, 95% CI 1.14-3.14, p<0.05), lymphoma (SIR 3.45, 95% CI 2.31-4.96, p<0.05), and leukemia (SIR 26.87, 95% CI 22.69-31.59, p<0.05) was observed. There was no statistically significant difference in SIR based on sex, race, marital status, follow-up duration, and receipt of chemotherapy. The risk was significantly higher in patients ≤60 years vs patients >60 years (SIR 2.34, 95% CI 1.89-2.86 vs SIR 1.86, 95% CI 1.65-2.10, p 0.01) and for PMF diagnosed after 2009 vs ≤2009 (SIR 2.64, 95% CI 2.26-3.07 vs SIR 1.61, 95% CI 1.40-1.85, p<0.001). Conclusions: Patients with PMF are at a high risk of developing SPM, especially leukemia and lymphoma. Data suggests higher incidence of SPM in patients aged ≤60 years and in the decade after 2009. The impact of ruxolitinib, which was approved in 2011, on the incidence of SPM deserves further study. [Table: see text]
Race/ethnicity and outcomes in hematopoietic stem cell transplantation (HCT) in myeloproliferative neoplasms (MPN): A single institutional study.
Authors: Ananth Snegha , Shaughnessy Paul , Zoghi Behyar , Gelfond Jonathan , Mesa Ruben A.
Published: June 2022

e19083

Background: Previous studies have demonstrated racial disparities in MPN outcomes, but there is no data regarding impact of race on outcomes of HCT in MPN. This is a retrospective study evaluating transplant related outcomes in Hispanics undergoing allogeneic HCT for MPN/MF in a large hospital in South Texas. Methods: A total of 45 patients who underwent HCT for MPN disorders from January 2008 to December 2020 at the Methodist Hospital, San Antonio were included. Race was self-reported by patients and obtained from electronic medical record along with other variables. Significance of variation in categorical outcomes were assessed with Chi-square tests. OS was estimated using the Kaplan-Meier method and compared between races using the log rank test. Results: This study analyzed 19 Non-Hispanic White (NHW) and 19 Hispanic (H) patients (7 patients were excluded due to unknown or other race). Patients primarily underwent transplantation for Myelofibrosis (n=19) followed by CMML (n=12) and MDS-MPN-U (n=7). There were no significant differences between NHW and H patients with regards to performance status, conditioning regimen, stem cell source and GvHD prophylaxis. However, H were younger at transplant with a median of 52 years (range 42-71) compared with 62 years (41-76) in NHW (p=0.50) and were more likely to have a haploidentical donor (47% vs 11%, p < 0.001). There were no significant differences in time to neutrophil (median 22 days (range 15-560) versus 25 days (range 8-48 days), p=0.7) or platelet recovery (median 24 days (range 15-636) versus 25 days (range 6-102), p=0.9) in NHW vs H patients. There were no significant differences in cumulative incidence of grade 1-2 and grade 3-4 acute GvHD between NHW (50 and 50%) vs H (40 and 60%) patients (p=0.4 and p=0.5, respectively). There was significant difference in the cumulative incidence of chronic GvHD (68% NHW compared to 37% H, p=0.03). Median OS was 6.75 years in NHW and 2.67 years in H (p=0.08). The cumulative incidence of Relapse Mortality (RM) and non-RM were not statistically significant between NHW and H, however H had higher percentage of relapse related mortality at 5 years (5.3% vs 17.5%)(Table). Among the 5 NHW and 8 H non-relapse deaths, causes of death were similar among the two groups – the most common being infection (20% and 38%, respectively), acute and chronic (40% and 25%) GvHD and graft failure (0% and 25%). Conclusions: NHW and H had comparable relapse, non-relapse and survival rates likely due to similar access to treatment and follow-up within a single institution. Larger and prospective studies are needed to further elucidate this important topic.[Table: see text]
Midostaurin in advanced systemic mastocytosis: A systematic review and meta-analysis.
Authors: Abuhelwa Ziad , Beran Azizullah , Kahlon Navkirat , Sayeh Wasef , Khokher Waleed , Assaly Ragheb , Hamouda Danae M.
Published: June 2022

e19084

Background: Midostaurin, an oral multikinase inhibitor including inhibition of KIT D816V, is approved for the treatment of advanced systemic mastocytosis (SM). Few studies have investigated the use of midostaurin in patients with advanced SM, but the data on its efficacy and safety in this population remains limited and uncertain. Therefore, we conducted this systematic review and meta-analysis to better assess the efficacy and safety of midostaurin in advanced SM. Methods: We systematically searched the following databases: PubMed/MEDLINE, Embase, and Cochrane through February 02, 2022, to include all studies that assessed the effect of midostaurin on clinical outcomes of patients with advanced SM. Our primary outcome was the overall response rate (ORR). The secondary outcomes included the rates of progressive disease (PD), stable disease (SD), and treatment discontinuation due to adverse events (AEs). All statistical analyses were performed using Open Meta Analyst (CEBM, University of Oxford). Pooled rates and corresponding 95% confidence intervals (CI) were calculated using DerSimonian-Laird/Random-effects approach. Results: Four studies (two clinical trials and two observational studies) with a total of 156 patients with advanced SM were included in the pooled analysis. The mean age of the patients was 59.6±15.8 years, and males represented 64.7% of total patients. The most common subtype of advanced SM was SM associated with hematological neoplasm (59%) followed by aggressive SM (23.1%). Three studies reported the KIT D816V mutation status, and 85.2% of patients were positive for KIT D816V mutation. The mean duration of treatment with midostaurin was 10±15.3 months. The pooled ORR was 60% (95% CI 46.5%-73.5%) over a mean follow-up duration of 41.1±38.7 months. The PD and SD rates were 12.8% (95% CI 7.6%-18%) and 10.6% (5.3%-15.9%), respectively. Treatment discontinuation due to AEs occurred in 25.6% (95% CI 18.8%-32.4%). The most common hematological grade ≥3 treatment-related AE was anemia (29%), while fatigue (7.1%) was the most common non-hematological grade ≥3 treatment-related AE. Conclusions: Our study demonstrated that midostaurin is very effective in patients with advanced SM with an acceptable safety profile. Our meta-analysis is hampered by a limited number of studies, a small sample size, and a lack of a control group. Future large-scale comparative studies are warranted to evaluate the efficacy and safety of midostaurin in these patients.
Network meta-analysis of progression free survival in the treatment of relapsed or refractory chronic lymphocytic leukemia.
Authors: Chanan-Khan Asher , Liu Tom , Yang Keri , Cohen Aileen , Fahrbach Kyle , Campbell Joanna , Tang Boxiong
Published: June 2022

e19514

Background: Zanubrutinib, a next-generation Bruton’s tyrosine kinase inhibitor (BTKi), demonstrated superior overall response rate and a trend toward improved progression-free survival (PFS) as compared to ibrutinib in patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) in the phase 3 ALPINE trial (NCT03734016) based on interim analysis. However, its comparative efficacy with other treatments is not known. The goal of this study was to estimate the relative efficacy of zanubrutinib compared with standard treatments for R/R CLL through a network meta-analysis (NMA). Methods: The efficacy of zanubrutinib from ALPINE (study of zanubrutinib and ibrutinib in patients with R/R CLL was compared to ibrutinib, acalabrutinib, bendamustine and rituximab (BR), and venetoclax + rituximab (V+R) using data from 4 RCTs. Relevant RCTs were identified using a systematic literature review. A network was constructed that composed RCTs (ALPINE, ELEVATE-RR [NCT02477696], ASCEND [NCT02970318], and MURANO [NCT02005471]). Bayesian network meta-analysis (NMA) models were used to simultaneously synthesize hazard ratios (HRs) and 95% credible intervals (CrIs) for investigator-assessed PFS and overall survival (OS) to estimate the relative efficacy of zanubrutinib versus comparators of interest. An assumption of constant hazard ratio was applied in the NMA analysis. Analyses were performed using well-established codes published by the National Institute for Health and Care Excellence (NICE) Decision Support Unit and were implemented with OpenBUGS (version 3.2.3). Results: The NMA suggested a significant improvement in PFS for zanubrutinib over acalabrutinib (HR=0.52, 95% CrI [0.30, 0.90]), ibrutinib (0.47, [0.29, 0.76]), and BR (0.13, [0.06, 0.26]). Zanubrutinib had a numerically better PFS than V+R (0.69, [0.32, 1.46]) while not reaching statistical significance. For OS, NMA results showed a trend favoring zanubrutinib over acalabrutinib (0.75, [0.35, 1.59]), ibrutinib (0.62, [0.31, 1.22]), and BR (0.52, [0.21, 1.24]). The difference was not statistically significant with wide CrIs, suggesting a high uncertainty as inherent limitation of the analysis. Conclusions: This NMA reports the first summary of comparative PFS of available treatments for R/R CLL. Indirect treatment comparisons suggest PFS on zanubrutinib may be superior to other BTKis and immunochemotherapies in R/R CLL patients.[Table: see text]
Efficacy of first-line treatment for chronic lymphocytic leukemia: A Bayesian network meta-analysis.
Authors: Chanan-Khan Asher , Yang Keri , Liu Tom , Cohen Aileen , Fahrbach Kyle , Wang Yunyang , Tang Boxiong
Published: June 2022

e19526

Background: Zanubrutinib is an oral, highly selective, next-generation Bruton tyrosine kinase inhibitor. Efficacy of zanubrutinib was compared with bendamustine + rituximab (BR) in adult patients with treatment-naïve (TN) chronic lymphocytic leukemia (CLL) in the phase 3 SEQUOIA trial (NCT03336333). However, efficacy of zanubrutinib compared with other frontline CLL treatments remains unknown. The goal of this network meta-analysis of randomized controlled trials (RCTs) was to estimate the relative efficacy of zanubrutinib compared with standard frontline treatments for CLL. Methods: A total of 4 relevant RCTs were identified by a targeted literature review conducted throughout January 2022, CLL11 (NCT01010061), ALLIANCE (NCT01886872), MABLE (NCT01056510), and SEQUOIA. A feasibility assessment was performed to ensure that RCTs included within each population strata did not differ with respect to effect modifiers including presence of mutation, age, del11, and del17 status. A network was constructed for the composed 4 RCTs to compare the efficacy of zanubrutinib with bendamustine + rituximab, chlorambucil + obinutuzumab, chlorambucil + rituximab, and ibrutinib in patients with previously untreated CLL. Bayesian NMA models were conducted to simultaneously synthesize hazard ratio (HR) and 95% credible intervals (CI) for investigator-assessed progression-free survival (PFS). A constant hazard ratio was assumed in the NMA analysis. Statistical analyses were performed using codes suggested by the National Institute for Health and Care Excellence. Results: The efficacy results of the NMA indicated a statistically significant improvement in PFS for zanubrutinib over bendamustine + rituximab (HR=0.42; [95% CI=0.27, 0.65]), chlorambucil + obinutuzumab (0.45 [0.23, 0.86]), and chlorambucil + rituximab (0.22 [0.12, 0.41]). Zanubrutinib achieved comparable PFS to ibrutinib (1.07 [0.59, 1.94]). Conclusions: This is the first NMA to compare the efficacy of zanubrutinib with all commonly utilized first-line treatment for TN CLL. Results from this indirect treatment comparison suggested that the PFS for zanubrutinib may be statistically significantly better than immunochemotherapy. Findings from this study require validation with further large scale RCTs with longer follow up time.[Table: see text]
Radiation therapy and associated cardiovascular outcomes in patients with Hodgkin’s lymphoma.
Authors: Dalal Shivani , Patel Krunalkumar , Hussein Atif Mahmoud , Gattas Boula , Patel Akash , Dalal Misha , Nguyen Thanh , Patel Umang
Published: June 2022

e19528

Background: Hodgkin’s lymphoma (HL) is a lymphoid neoplasm, with lymphadenopathy with constitutional symptoms as presenting manifestations. The treatment is guided by the clinical stage of disease, and is curable in about 75% of the patients. Advances in cancer therapeutics have improved survival rates, however treatment-related toxicities have become a competing cause of late mortality. Radiation therapy (RT) and chemotherapy have historically been the pillars of curative treatments for HL. RT to the thorax is associated with substantial risk for the development of cardiovascular (CV) disease including pericardial disease, coronary artery disease, valvular disease, conduction disease, cardiomyopathy. The true incidence of radiation-related cardiovascular disease remains uncertain due to lack of large multi-centre studies with a sufficient duration of CV follow-up. Through this study we aim to determine the CV co-morbidities and outcomes of patients with HL treated with and without RT. Methods: We identified hospitalized adult patients with HL and divided them into patients with and without history of radiation therapy from October 2015 to December 2018 from the National Inpatient Sample Database using ICD 10 codes. We further determined demographics, baseline characteristics, associated CV co-morbidities, mortality, length of stay and hospitalization costs among patients with HL with and without history of RT. SAS 9.4 software was used for statistical analysis. Results: We captured 86,325 patients hospitalized with HL during the study period out of which 11,030 patients had history of RT. The patient cohort with RT was noted to have higher prevalence of hypertension (40.7 vs 37.1%), heart failure with reduced ejection fraction (9.2 vs 6.4%), heart failure with preserved ejection fraction (9.2 vs 5.9%), coronary artery disease (33.6 vs 20.3%), atrial fibrillation (19.2 vs 14%), aortic valve disease (10.1 vs 3.8%), mitral valve disease(5.6 vs 2.7%), pulmonary hypertension (9.6 vs 4.6%), and pleural effusion(9.7 vs 6.8%) as compared to patients without history of RT. The study did not show any statistically significant difference in length of stay or in-hospital mortality in the two groups. Conclusions: This study revealed significantly higher prevalence of multiple CV co-morbidities among HL survivors treated with RT. CV disease is now the most common non malignancy related cause of death in radiation-treated cancer survivors. Awareness and early identification of cardiac complications is crucial survivors. There are currently no consensus guidelines to dictate the optimal surveillance of recipients of thoracic radiation. Therefore through this study we aim to shine light on the importance of early surveillance and collaboration between oncologists and cardiologists in the management of the cancer survivors with history of RT.
Predictors of secondary lung cancer among Hodgkin lymphoma survivors: A nationwide analysis.
Authors: Alnimer Yanal Mufeed , Mustafa Ali Moaath Khader
Published: June 2022

e19529

Background: There is insufficient data regarding the incidence rate of secondary lung cancer among Hodgkin lymphoma survivors and the predisposing factors. Methods: We analyzed the data from the cohort of subjects who had Hodgkin Lymphoma between 1973 and 2015 using the Surveillance Epidemiology and End Results database (SEER). Data on patient's age, gender, year of diagnosis with Hodgkin lymphoma, Ann-Arbor stage, Histology, racial groups, date of last follow-up, date of death, and treatment modalities were collected. Results: We identified a total of 56,856 subjects with Hodgkin lymphoma; of those, 862 had secondary lung cancer, with an incidence rate of 157 (95%CI: 147-168) per 100,000 person-years. The median overall survival from time of Hodgkin Lymphoma diagnosis for those with secondary lung cancer was 12.1 years (95%CI: 10.7-13) compared to 27.1 years (95%CI: 26.5-27.6) for those who did not develop lung cancer. After propensity score weighting, radiation therapy was associated with a higher risk of secondary lung cancer (HR: 1.23, 95%CI: 1.002-1.55). Older age at the time of Hodgkin lymphoma diagnosis and male gender were associated with higher risk, with an HR of 1.07 (95%CI 1.062-1.073) and an HR of 1.602 (95%CI 1.33-1.94), respectively. Furthermore, chemotherapy increases the risk only among older age groups. Conclusions: Older age at the time of Hodgkin Lymphoma diagnosis, male gender, radiation therapy and chemotherapy only among older age groups were associated with higher risk for secondary lung cancer, with 50% of the cases occurring within 9.1 years following Hodgkin lymphoma diagnosis.[Table: see text]