bluuebunny/crossref_metadata_2025 huggingface dataset:
Economic evaluation of the oncotype DX test for hormone receptor positive (HR+) early-stage breast cancer (BC) from the Brazilian societal perspective.
Authors: Mattar Andre , Fonseca Guilherme Ribeiro , Romão Murilo Barato Agudo , Shida Jorge Yoshinori , Jakubowski Debbie M , Chao Calvin Y. , Oliveira Sergio C , Gebrim Luiz Henrique
Published: May 2020

e19380

Background: Selecting appropriate patients for AC (adjuvant chemotherapy) remains an important issue in BC treatment. Although AC improves clinical outcomes toxicity and economic burden is substantial. The Oncotype DX test identifies high-risk patients likely to benefit from AC who otherwise might not be identified through standard parameters (SP), and low-risk patients unlikely to benefit from AC, avoiding toxicities and inherent risks. This study estimated the incremental cost-effectiveness ratio and budget impact (BI) of Oncotype DX testing from the perspective of the Brazilian Public Health System. Methods: A Markov transitional state model was developed with 3 states: recurrence free, distant recurrence, and death. The model compared the scenario in which patients are screened by SP with a proposed scenario with Oncotype DX testing. Changes in therapeutic recommendations and cost of treatment were obtained from a prospective clinical survey at Pérola Byington Hospital. Additional data was obtained from literature. As a societal perspective analysis, medical costs (test, AC, and adverse events), costs of productivity loss, transportation and employment leave were considered. Population was estimated from BC incidence, proportion of early stage cases, and HR expression. An incremental proportion of 10% per year of patients using Oncotype DX testing was assumed. BI analysis had a 5-year horizon and cost-effectiveness a lifetime horizon (5% annual discount). Results: Oncotype DX results as identifier of a subgroup at higher risk of relapse and greater benefit with AC was dominant over SP. Oncotype DX testing resulted in clinical benefits in terms of life-years gained (0.62) and quality-adjusted life years (0.54), related to lower incidence of distant recurrence and use of AC, both of which greatly impacted quality of life. Testing resulted in economic benefits, with lower average cost per patient (−BRL 3,855). Incorporation of Oncotype DX testing resulted in potential savings reaching BRL 107 million in the 5th year stemming from the decrease in AC and consequent decrease in indirect costs. Conclusions: Patients with HR+, HER2− early stage BC may present different risks of relapse and likelihoods of benefiting from AC. With high clinical impact for patients and high economic impact for the health system, a tool that safely and accurately identifies the subgroup of patients who really needs AC is essential. Oncotype DX test incorporation in the Brazilian Public Health System should be considered.
Cost effectiveness of combination ipilimumab-nivolumab in advanced non-small-cell lung cancer.
Authors: Courtney Patrick T , Yip Anthony T , Cherry Daniel R , Salans Mia A , Kumar Abhishek , Murphy James Don
Published: May 2020

e19387

Background: The combination of nivolumab and ipilimumab was found to improve overall survival compared to chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC) in the Checkmate 227 trial. However, nivolumab and ipilimumab are significantly more expensive than chemotherapy, and given the high incidence of advanced lung cancer, incorporating dual checkpoint inhibitors into the standard of care could have substantial economic consequences. In this study, we evaluated the cost effectiveness of combination ipilimumab and nivolumab for the treatment of advanced NSCLC. Methods: We designed a Markov model simulating the three treatment arms of the Checkmate 227 trial: nivolumab plus ipilimumab, nivolumab monotherapy, and chemotherapy. Transition probabilities, such as disease progression, survival, and treatment toxicities, were derived from trial data. Costs (in 2019 United States dollars) and health utilities were estimated from published literature. Incremental cost-effectiveness ratios (ICERs), expressed as dollar per quality-adjusted life-year (QALY), were calculated, with results less than $100,000/QALY considered cost-effective from a healthcare payer perspective. We assessed model uncertainty with one-way and probabilistic sensitivity analyses. Results: In our base-case model, nivolumab and ipilimumab combination therapy increased overall cost by $227,700 and improved effectiveness by 0.55 QALY compared to chemotherapy, resulting in an ICER of $413,400/QALY. Nivolumab monotherapy increased overall cost by $98,500 and improved effectiveness by 0.05 QALY compared to chemotherapy, resulting in an ICER of $1,885,400/QALY. Our model was most sensitive to both the cost and duration of dual immunotherapy. Combination immunotherapy became cost effective at an ICER under $100,000/QALY if monthly costs of treatment were reduced from $26,586 to $8,844 (a 67% reduction) or if maximum allowed duration of immunotherapy was reduced from 24 to 4 months. The model was not sensitive to assumptions about survival differences between the study arms. Probabilistic sensitivity analysis showed that at a willingness-to-pay threshold of $100,000/QALY, dual immunotherapy was less cost-effective than chemotherapy 99.99% of the time. Conclusions: Combination nivolumab and ipilimumab immunotherapy is not cost-effective at current prices despite increasing overall survival for patients with advanced NSCLC.
Examining perceptions of financial toxicity among cancer patients: The Financial Toxicity 16 Questionnaire.
Authors: Bordonaro Roberto , Castagna Fabrizio , Piazza Dario , Cordio Stefano Sergio , Sergi Concetta , Fassari Giuseppina Emanuela , Martines Concetta , Commendatore Oriana , Sambataro Daniela , Carapezza Luigia , Mattina Marco , Russo Alessia Erika , Gebbia Vittorio
Published: May 2020

e19389

Background: Financial toxicity (FT) among cancer patients (CP) is multifactorial, arising from both disease-related and non- disease related factors, including socio-cultural, environmental, and psychological attributes. It derives both from costs related to assistance and borne on the patients and its caregivers, and reduction of income capacity also in this case borne on the patients and on the caregivers. Stress levels may escalate to significant proportions in some patient, to present with symptoms of anxiety especially during therapy administration periods. Methods: In order to highlight financial toxicity related to the diagnosis of metastatic pancreatic and lung cancer and to measure its evolution over time and any correlation with the prognosis, we developed a questionnaire called FT16 and we conducted a validation study on a sample of 31 patients. The design of the study involved the development and the psychometric assessment of a scale to measure the perceived sources of FT among CP. Following extensive literature review, a table of specification with the initial items was created to guide item construction for developing the scale. The items related to these FT were converted into an 16-item, multipoint questionnaire, resulting in the FT16. We also monitored quality of life of the patients, using the QlQ C-30 questionnaire, in the aim to capture correlation between FT onset and quality of life deterioration; clinical characteristics of the patients, response to therapy and outcome parameters also have been recorded in the aim to evaluate eventual correlation with FT. Results: The questionnaire was administered to 31 adult patients with lung and pancreatic metastatic cancer, both men and women, who were newly diagnosed and will undergo cancer treatment. Each of them has been informed about the research and written informed consent has been obtained. The internal consistency reliability (Cronbach’s alpha) was 0.77 for the 16 items of the FT16. Analyses of variance (ANOVAs) indicated that there were no significant differences in the mean FT16 score, between sexes, and age groups in the severity score. Conclusions: FT16 questionnaire seems to be an useful tool to capture FT onset in this poor-prognosis subset of patients; the analysis of the data recorded will continue to assess the capability of the FT16 to capture correlations with clinical characteristics at diagnosis and correlations with the prognosis.
Cost-effectiveness of first-line therapy for advanced renal cell carcinoma in the immunotherapy era.
Authors: Parikh Divya Ahuja , Serrato Paul Irvin , Srinivas Sandy , Ryckman Tess Sophie , Salomon Joshua , Goldhaber-Fiebert Jeremy D
Published: May 2020

e19392

Background: The treatment landscape for advanced renal cell carcinoma (RCC) has transformed in the past two years. Both Nivolumab plus Ipilimumab and Pembrolizumab plus Axitinib are approved regimens for first-line treatment of intermediate to poor-risk patients with advanced RCC. The choice between these immunotherapy-based combinations for first-line therapy is highly debated; no prior study has evaluated the cost-effectiveness of both combinations compared to Sunitinib. Methods: We used a decision analytic Markov model informed by the recent Checkmate-214 and Keynote-426 phase 3 randomized controlled clinical trials to evaluate costs and effectiveness of Nivolumab plus Ipilimumab, Pembrolizumab plus Axitinib, and Sunitinib in the first-line treatment of advanced RCC from a US health payer perspective. We used the model to extrapolate survival beyond the closure of the trials and examined the robustness of our findings with sensitivity analyses. Main outcomes were life expectancy, quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios, all discounted at 3% annually. Results: Nivolumab plus Ipilimumab increased life expectancy by 0.58 years at cost of approximately $190,000 per QALY gained compared to Sunitinib. Pembrolizumab plus Axitinib increased life expectancy by 0.39 years at a cost of approximately $861,000 per QALY gained compared to Nivolumab plus Ipilimumab. The results were not sensitive to reasonable changes in drug costs and quality of life estimates. Both combinations cost more than the traditional willingness-to-pay threshold (WTP) of $150,000 per QALY gained. A 20% price reduction is required for Nivolumab and Ipilimumab to be cost-effective and a 48% price reduction is required for Pembrolizumab plus Axitinib to be cost-effective. Conclusions: Both Nivolumab plus Ipilumumab and Pembrolizumab plus Axitinib provide increased longevity and reduced morbidity relative to Sunitinib. However, the prolonged duration of treatment and doublet-drug pricing results in high-costs. Price reductions are required for both of the immunotherapy-based combinations to be cost-effective. [Table: see text]
Cost effectiveness analysis of additional NK-1 receptor antagonist to olanzapine, ondansetron, and dexamethasone for prevention of chemotherapy-induced nausea and vomiting in patients receiving high-dose cisplatin.
Authors: Mahaparn Wasamol , Lertanansit Chalermchai , Vinayanuwattikun Chanida , Tanasanvimon Suebpong
Published: May 2020

e19398

Background: NK-1 receptor antagonist (NK1RA) is a standard anti-emetic agent in chemotherapy-induced nausea and vomiting (CINV) prevention in patients receiving high-dose (HD) cisplatin. However, in limited-resource settings, three-drug regimen including olanzapine, ondansetron and dexamethasone is affordable and effective in CINV prevention in these patients. Objectives: To evaluate cost effectiveness of additional NK1RA for CINV prevention in Thai patients receiving HD cisplatin in 3-cycle horizon, societal perspective. Methods: During January to December 2019, 20 patient receiving HD cisplatin were prospectively enrolled to receive standard three-drug regimen at King Chulalongkorn Memorial Hospital. Total medical resource utility, non-medical cost and clinical outcomes were actually collected and used for establishing decisional-tree model and cost-effectiveness analysis. Three arms decisional-tree model was constructed. First, standard strategy, a real-world practice in Thailand, patients received three-drug regimen in all cycles of chemotherapy. Second, NK1RA-rescue strategy, patients received three-drug regimen in the first cycle and additional NK1RA in subsequent cycles if the patients experienced CINV. Third, NK1RA upfront strategy, patients received four drug NK1RA-containing regimen in all cycles. Complete response (CR) rate was assumed to be 92.5% in NK1RA-containing regimen based on clinical trials. The study endpoint is to compare cost and QALYs in term of incremental cost-effectiveness ratio (ICER). Results: CR rates were 90% and 71% in first and second cycle in patients receiving standard regimen. The NK1RA upfront strategy produced greatest QALYs of 0.0351, followed by 0.0328 and 0.0292 in NK1RA-rescue strategy and standard strategy respectively. Mean total costs were 10420.46, 3332.19 and 2841.30 Thai baht (THB) respectively. The ICER of NK1RA-rescue strategy relative to standard strategy was 135,774 THB per QALY and the ICER of NK1RA upfront strategy relative to NK1RA-rescue strategy was 3,096,654 THB per QALY. Therefore, the ICER of NK1RA-rescue strategy but not NK1RA upfront strategy is considered to be cost effective at the willingness-to-pay level of 160,000 THB per QALY. Conclusions: Our findings suggested that the additional NK1RA as a rescue strategy is cost-effective in patients receiving HD cisplatin in Thai health care.
Cost-effectiveness of filgrastim-sndz as primary prophylaxis (PP) versus secondary prophylaxis (SP) to prevent chemotherapy-induced febrile neutropenia (FN) in non-small cell lung cancer (NSCLC) patients at intermediate risk.
Authors: Li Edward C. , Mezzio Dylan , Spargo Andrew , Campbell Kimberley J. , Lyman Gary H.
Published: May 2020

e19401

Background: Patients with nonmetastatic NSCLC receiving platinum-based chemotherapy are at an intermediate risk (10-20%) of developing FN; clinical practice guidelines recommend assessing whether these patients have FN risk factors before considering myeloid growth factor (MGF) prophylaxis. Most NSCLC patients receiving chemotherapy have ≥1 FN risk factors, and while PP leads to lower rates of FN across all cycles, it is more costly compared to SP. This study evaluates the cost-effectiveness of PP vs. SP using a biosimilar MGF, filgrastim-sndz, in NSCLC patients at intermediate risk of FN. Methods: A Markov model with a lifetime horizon was constructed to evaluate the total costs and clinical outcomes of using filgrastim-sndz as PP vs. SP in NSCLC patients 61 years old receiving adjuvant carboplatin/paclitaxel every 3 weeks for 4 cycles. Separate analyses were conducted for patients with 0 FN risk factors (0RF) and with ≥1 FN risk factors (1+RF), representing 11.3% and 18% baseline FN risk, respectively. Incremental cost-effectiveness ratios (ICERs) were calculated for cost per FN event avoided, life-year saved (LYS), and quality-adjusted life-year (QALY) gained from a United States payer perspective. Deterministic and probabilistic sensitivity analyses (PSA) were conducted. Results: For patients with 0RF, use of filgrastim-sndz as PP vs. SP provided an additional 0.056 QALYs (0.079 LYS) at an incremental cost of $3,266. The ICERs were $46,815, $41,555, and $58,531 for cost per FN event avoided, cost per LYS, and cost per QALY gained, respectively. For patients with 1+RF, PP vs. SP added 0.090 QALYs (0.127 LYS) at an incremental cost of $1,605. The ICERs were $13,970, $12,644, and $17,805 for cost per FN event avoided, cost per LYS, and cost per QALY gained, respectively. In the PSA, the likelihood of cost-effectiveness at a willingness-to-pay (WTP) threshold of $50,000 per QALY gained was 31.7% for patients with 0RF and 96.6% for 1+RF. Conclusions: For NSCLC patients at intermediate risk of FN receiving adjuvant carboplatin/paclitaxel with 1+RF, PP with filgrastim-sndz compared to SP is cost-effective based on a WTP threshold of $50,000/QALY. [Table: see text]
Financial toxicity and its associated patient and cancer factors among women with breast cancer in China.
Authors: Jing Jingfeng , Feng Ran , Zhang Xiaojun , Li Ming , Gao Jinnan
Published: May 2020

e19402

Background: The term “Financial toxicity(FT)” is widely used to describe the distress or hardship patients suffering from the financial burden of cancer treatment[1]. Increased evidences have showed that cancer-associated FT is common and has a negative impact on patients’ mental health, quality and length of life[1,2]. The scale of COmprehensive Score for financial Toxicity-Functional Assessment of Chronic Illness Therapy (COST-FACIT) was used to assess the FT of cancer patients, which has been validated and widely used internationally [3] and China [4]. To our knowledge, little is known about the FT of breast cancer patients in China. The aim of this study is to assess the FT and to investigate patients and cancer characteristic that associated with it in patients in central China. Methods: This was a cross-sectional study among 188 patients with stage 0-III women breast cancer admitted in Bethune hospital in Taiyuan, Shanxi province during January - May 2019. FT was self-reported using the COST-FACIT. Patients’ socio-demographic factors, clinical examination, and cancer treatment were collected from questionnaire and hospital record. The financial concern and coping strategy was self-reported. Factors associated with FT was identified using linear regression analysis. Results: One hundred and sixty-six (88.2%) completed the questionnaire. The COST score ranged 0-40 with a mean of 21.2 (median 22.5, standard deviation 8.1). On multivariate linear regression analysis, older age (β coefficient: 0.19, 95% CI: 0.10-0.29, p<0.001), higher household income (β coefficient: 3000-5000 Yuan: 6.48, 95% CI: 2.78-10.17, p =0.001; ≥ 5000 Yuan: 11.17, 95% CI: 7.25-15.09, p<0.001) were positively associated with COST scores. Advanced cancer stage was the strongest predictor of FT among the cancer characteristics (β coefficient: -1.81, 95% CI: -3.17, -0.46, p=0.009). To cope with the FT, 131 (78.8%) patients decreased non-medical expenses, and 56 (33.7%) reduced or quit treatment. Conclusions: FT was significantly associated with patient’s age, income, and cancer stage. Women having financial concerns after diagnosis were more likely to reduce their non-medical expenses and even quit treatments. Clinicians should take into account the FT levels in all patients and work out appropriate treatment strategies for optimal clinical outcome.
The evolution of financial toxicity in patients with lung cancer.
Authors: Friedes Cole , Hazell Sarah , Fu Wei , Hu Chen , Lee Beverly , Voong K Ranh , Feliciano Josephine Louella , Nicholas Lauren , McNutt Todd R. , Han Peijin , Hales Russell K.
Published: May 2020

e19406

Background: Financial toxicity (FT), or the cost-related side effect of cancer therapy, has been linked to poor clinical outcomes, greater symptom burden, and worse quality of life. While the repercussions of FT have been thoroughly explored, the longitudinal patient relationship with FT in the initial course of therapy is unknown. Methods: Patients with stage II – IV lung cancer were recruited in a prospective longitudinal non-interventional study between July 2018 and January 2020. FT was measured via the COST score, a validated questionnaire for benchmarking FT, at a) the time of cancer diagnosis and then later at b) 6-month follow up (6MFU). In this model, a lower COST score indicates increased financial hardship. Completed 6MFU data was compared to corresponding baseline data for each patient. Linear regression analysis was used to compare patient characteristics with baseline COST (COSTbase) and 6-month COST (COST6M) scores. Results: At the time of analysis, 209 patients were screened and 194 (95.1%) patients agreed to participate and complete the baseline survey. Subsequently, 93 patients completed the 6MFU survey, 32 patients had died, and 7 patients were lost to follow up. The remaining 62 patients have not met the study end point to date. Of the 93 patients that completed the 6MFU and baseline survey, the median age was 65 (range 35-89), 50.5% were male, and 76.3% were Caucasian. Over the first six months of therapy 36.5% overestimated OOP expenses by > $1000 and 22.5% reported a decrease in total monetary savings, but only 4.3% of patients made decisions about health care based on cost of care. FT was present at both time points but was worse at diagnosis than at 6MFU (median COSTbase 25 [range 1-44] vs. median COST6M 27 [range 0-44]; p = 0.04). Linear regression correlated risk factors with FT at baseline ( < 1 month monetary savings, employed but on sick leave, and inability to afford basic necessities; all p < 0.001) that were different from risk factors at 6MFU (paying much more than expected OOP and sacrificing spending to meet medical costs; p < 0.001). There was no significant difference between estimated OOP costs at baseline (median $2550 [range $0 - $500,000]) and actual OOP costs (median $2496 [range $0 – 25,900]; p = 0.25). Conclusions: FT toxicity is pervasive at both diagnosis and at 6-month follow up, however, the magnitude of toxicity changes with time. Few patients are willing to sacrifice medical care regardless of the cost. Risk factors for FT evolve, suggesting that different groups may benefit from financial intervention at diagnosis versus 6MFU.
Real-world healthcare resource utilization and costs among relapsed/refractory (R/R) mantle cell lymphoma (MCL) patients receiving ibrutinib or chemoimmunotherapy (CIT).
Authors: Ghosh Nilanjan , Emond Bruno , Lafeuille Marie-Hélène , Côté-Sergent Aurélie , Lefebvre Patrick , Huang Qing
Published: May 2020

e19408

Background: Ibrutinib is a targeted oral therapy indicated for MCL patients who received ≥1 prior line of therapy (LOT) (conditional approval on 11/13/2013 in the US). This study compared healthcare resource utilization (HRU) and costs of R/R MCL patients treated with ibrutinib ± rituximab (I±R) or CIT in a US-managed care population. Methods: Optum Clinformatics Extended DataMart De-Identified Databases (05/13/2013-6/30/2019) were used to identify adults with MCL receiving I±R or CIT (index date) following ≥1 prior LOT. Patients’ baseline characteristics were balanced using inverse probability of treatment weighting (IPTW). Monthly HRU and costs (plan paid amount) were evaluated during the first Oncology Care Model (OCM) episode (i.e., first 6 months) post-index and during the observed index I±R or CIT LOT (index LOT); and compared using rate ratios (RRs) and mean monthly cost differences (MMCDs), respectively. Results: A total of 146 I±R and 158 CIT patients were identified. Given the small sample size and to ensure outliers were not driving the results, 2 patients with total healthcare costs ≤0.5th and ≥99.5th percentile were excluded from each cohort. After IPTW, 149 and 151 patients were included in the weighted I±R and CIT cohorts, respectively (mean length of index LOT: 12.0 vs 11.0 months). During the first OCM episode and during the index LOT, the I±R cohort had significantly fewer monthly days with outpatient services compared to the CIT cohort (OCM: RR= 0.63, P<0.001; index LOT: RR= 0.73, P=0.004). The I±R cohort incurred significantly higher monthly pharmacy costs that were offset by lower monthly medical costs, yielding a monthly total cost reduction of $9,435 (p<0.001) during the first OCM episode and $4,628 (p=0.010) during the index LOT, compared to the CIT cohort (Table). Conclusions: In this study, patients with R/R MCL treated with ibrutinib ± rituximab had significantly fewer days with outpatient services and lower total healthcare costs per month versus those treated with CIT during the first OCM episode and the index LOT. [Table: see text]
Post-transplant cyclophosphamide as graft-versus-host disease prophylaxis in HLA matched sibling donor stem cell transplantation for patients with acute leukemia.
Authors: Elshamy Alaa Nabil , Abdelmohsen Essam Ali , Denewer Mai , Mabed Mohamed Nasr
Published: May 2020

e19523

Background: Graft-versus-host disease (GVHD) is a life-threatening complication of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT). Calcineurin inhibitor (CNI) and methotrexate (MTX) have been used as the standard GVHD prophylaxis in HLA-matched HSCT. Promising clinical trial data using high dose post-transplant Cyclophosphamide (PT-Cy) with or without additional immunosuppressive agents (IS) have shown that it’s an effective, well tolerated alternative. However, experiences are limited with controversial results. Methods: We analyzed 62 patients with Acute Leukemia (39 males, 23 females) with age ranges from 18 to 60 years underwent allogeneic HSCT from matched sibling donors (MSD) using reduced intensity chemotherapy at Maadi Armed Forces Medical Hospital after informed consent. They were randomized into 2 groups according to GVHD prophylaxis regimen. The 1st group (40 patients) received MTX in the following doses; day+2 (15mg), day +4 (10 mg), day +6 (10 mg) with Cyclosporine (5mg/kg) from day -3 till day +90 and Mycophenolate (MMF) (2 -3gm/day) from day +1 till day +30. The 2nd group(22 patients) received PT-Cy (45 mg/kg/day) on days +3 and +4 with Cyclosporine (5mg/kg) from day +5 till day +30 & MMF:(2-3gm /day) from day +5 till +30. Results: At median 1 year Post Allo, PT-Cy was associated with statistically significant lowering of chronic GVHD (cGVHD) incidence compared to MTX group (22.7%, 56.4%) respectively (P = 0.011). Incidence of acute GVHD (aGVHD) at day +100 was (40%, 22.7%) in group 1, 2 respectively (P = 0.169). 92% of patients in group 1 and 86.4 % of patients in group 2 were engrafted with full donor chimerism on day +30 (P = 0.659). The cumulative incidence of relapse at 4 years after transplantation was 17.9 % for group 1 and 36.4 % for group 2 (P > 0.05). Relapse related mortality were 16.2% among MTX group while 27.3% in PT-Cy group (P = 0.10). Transplant related mortality (TRM) in MTX group were; Severe aGVHD (8%), cGVHD (10%), Hepatic Toxicity (8%), Nephrotoxicity (2.7%) & ARDS (5.4%). In PT-Cy group TRM were; septicemia (18%), severe aGVHD (4.5%) & ARDS (4.5%). Cumulative 4 years Disease Free Survival (DFS) & Overall survival (OS) in PT-Cy group were (51.8 %, 46.4%) respectively while (69.3%, 39%) in MTX group which is statistically non-significant (P > 0.05). Conclusions: For GVHD prophylaxis in MSD, PT-Cy is a safe alternative that reduces the risk of cGVHD in comparison with MTx based regimen without affecting Relapse rate, DFS or OS.
Single-institution experience of allogeneic stem cell transplantation for diffuse large B-cell lymphoma.
Authors: Puliafito Benjamin , Afshar Solmaz F. , Galitzeck Zachary , Steinberg Amir S.
Published: May 2020

e19524

Background: Given the promising results of novel therapies such as CAR-T, there is heightened scrutiny on the long-term outcomes of allogeneic stem cell transplant (alloHCT) in diffuse large B cell lymphoma (DLBCL). We present the characteristics and long-term follow-up of DLBCL patients (pts) who underwent alloHCT at our institution over the past 10 years. Methods: Adult pts who underwent an initial alloHCT for DLBCL at our institution from 2008 to 2018 (n = 18) were included. Pt, disease, transplant (tx), and GVHD history were retrospectively collected from reports to CIBMTR and chart review. Outcomes of progression-free survival (PFS) and overall survival (OS) were analyzed in February 2020. Results: Eighteen pts underwent an alloHCT for DLBCL at a median of 19.5 months post-diagnosis (range, 6 – 83 mo). The median age at the time of tx was 53 years old (range, 30 – 67 yrs). The median Karnofsky score was 70 (range, 30 – 100). The majority of the pts (78%) had stage IV disease. The median number of prior chemotherapy regimens was 3 (range, 1 – 6). Disease was chemosensitive in 11 pts (61%), chemoresistant in 4 pts (22%), and undetermined in 3 pts (16%). Eleven pts (61%) had a previous autoHCT with a median time between txs of 8 months (range, 4 – 28 mo). The disease status at time of tx included CR1 (n = 2), CR3+ (n = 2), PR (n = 4), PIF-resistant (n = 3), PIF-sensitive (n = 1), REL1-resistant (n = 1), and REL3+-sensitive (n = 3). Fifteen patients received PBSC and 3 patients received cord blood. Donors were HLA-identical siblings (n = 5), monozygotic twins (n = 1), and unrelated (n = 12). Conditioning regimens were Flu/Mel (n = 10), Flu/Mel/ATG (n = 2), Flu/TBI (n = 2), Flu/Cy/TBI (n = 1), Cy/TBI (n = 2), and BEAM (n = 1). Acute GVHD developed in 16 pts (89%) with max grades of III or IV in 10 pts despite 94% of pts receiving GVHD prophylaxis. Chronic GVHD developed in 5 pts (28%; 3 pts with limited disease and 2 pts with extensive disease). PFS rates were 56% at 6 months, 33% at 1 year, and 24% at 3 years. OS rates were 72% at 6 months, 39% at 1 year, and 24% at 3 years. The median time to death was 7.5 months (range, 1 – 74; mean 12.9 mo) with primary disease as the most common cause of death (5/18 pts; 28%). At the time of analysis, 4 pts (22%) were alive with a maximum survival of 58 months (range, 28 – 58 mo). Conclusions: A significant portion of DLBCL patients had durable responses after alloHCT with 24% of patients alive at 3 years, despite high rates of GVHD and a broad range of disease status. As novel therapies continue to emerge, alloHCT should still be considered in specific populations of relapsed and refractory DLBCL.
Phlebotomy requirements are lower in polycythemia vera patients with low ferritin stores.
Authors: Hammons Lindsay , Wu Lesley , Tremblay Douglas , Ronner Lukas , Ginzburg Yelena
Published: May 2020

e19537

Background: Polycythemia vera (PV) is a myeloid neoplasm of clonal red cell proliferation. Most PV patients are iron deficient at diagnosis, prior to the onset of therapeutic phlebotomy, the mainstay of treatment. More recent studies have also suggested that aberrant iron homeostasis contributes to persistently elevated hematocrit in iron deficient PV patients. In healthy individuals, iron deficiency leads to anemia such that the co-occurrence of polycythemia and iron deficiency in PV is pathological. The purpose of our study is to investigate whether iron deficiency, as defined by serum ferritin < 15 μg/L, at PV diagnosis can predict phlebotomy requirements in PV patients. Methods: 173 patients were diagnosed with PV between 2010 and 2019 at our institution. We analyze ferritin levels, phlebotomy frequency, and cytoreductive therapy in PV patients. Patients are stratified into a “high ferritin” (serum ferritin > 30 μg/L) or “low ferritin” (serum ferritin < 15 μg/L) groups and analyzed at 0-6 months and 4-6 years after diagnosis. 91% of PV patients were treated with phlebotomy and 70% with cytoreductive therapy. 23 and 13 patients had both a ferritin level and a record of the number of phlebotomies at 0-6 months or 4-6 years after diagnosis, respectively. Results: The average number of phlebotomies at 0-6 months after diagnosis was 3.1±1.7, with no statistically significant difference between the low and high ferritin groups. The average number of phlebotomies at 4-6 years after diagnosis was 2.9±2.5, with no statistically significant difference between the low and high ferritin groups (1.9 vs. 4.6 phlebotomies, respectively; p = 0.136). In patients with low ferritin at diagnosis, phlebotomy requirements decreased at 4-6 years relative to 0-6 months after diagnosis (1.9 vs. 3.1 phlebotomies; p = 0.009) while no difference occurred in the high ferritin group. In all PV patients, average serum ferritin increased with time from diagnosis (R = 0.81) and cannot be explained by cytoreductive therapy as there was no significant effect on average ferritin levels (137 vs. 60 μg/L; p = 0.295) or phlebotomy requirements (3.2 vs. 3.4; p = 0.803) at 4-6 years after PV diagnosis. Conclusions: Low ferritin levels at PV diagnosis decreased phlebotomy frequency at 4-6 years relative to 0-6 months after diagnosis. Additionally, cytoreductive therapy did not significantly affect phlebotomy requirements or ferritin levels at 4-6 years post-PV diagnosis. Further work is needed to assess the molecular pathways involved in iron-deficient erythrocytosis in PV.
Real-world disease burden for patients (pts) with myelofibrosis (MF) treated with ruxolitinib (RUX).
Authors: Gerds Aaron Thomas , Kish Jonathan , Parikh Kejal , Liassou Djibril , Miller Talia , Copher Ronda
Published: May 2020

e19539

Background: MF is an aggressive myeloid neoplasm and until recently RUX was the only treatment available. Real-world, long-term outcomes in pts with MF have not been described. Methods: Providers from multiple community oncology clinics in the USA reviewed the charts of consecutive pts with MF (primary or post-polycythemia vera/essential thombocythemia MF) who received RUX at any time from Jan 1, 2015 to Dec 31, 2017; data were collected Nov 15–26, 2019. Pt characteristics, treatment patterns, and outcomes (symptoms, blood counts, disease transformation) were retrospectively abstracted into an electronic case report form (eCRF) at each visit during the first 6 months, at any RUX dose modification; and at 12, 24, and 36 months post-RUX initiation. Pt characteristics, treatment patterns, rationale for dose modification, and treatment duration are described for pts during the first 6 months of therapy. Results: eCRFs were completed for 104 pts with MF treated with RUX. 42 pts received a RUX dose modification and 62 did not. Median follow-up from RUX initiation was 23.5 months. In the first 6 months of therapy, 40.4% of pts had a RUX dose modification (76.2% dose reduced; 23.8% dose increased). The most common reason (70%) for dose increase was titration to therapeutic dose. The most common reason (75%) for dose reduction was hemoglobin 8–10 g/dL or platelet count 50–75 × 109. The starting dose of RUX was higher for no RUX dose modification pts (mean total daily dose 34.9 mg vs 27.0 mg, P < 0.01). RUX dose-modified pts were older vs pts with no RUX dose modification ( P = 0.01); International Prognostic Scoring System (IPSS) risk score ( P = 0.89) and the proportion of pts with primary MF ( P = 0.06) were similar (Table). Overall, 64.4% of RUX treated pts discontinued therapy (RUX dose-modified 78.6%; no RUX dose modification 54.8%, P = 0.01). Median duration of RUX treatment was 11.0 months (RUX dose modified 10.6 months; no RUX dose modification 12.2 months; log rank P = 0.12). Conclusions: In this real-world study, 64.4% of pts discontinued RUX during follow-up. Higher rates of discontinuation and shorter time to discontinuation were noted for pts with a dose modification during the first 6 months of therapy. Given the short duration of therapy observed in this study as compared with published clinical trials, additional MF treatments are needed that offer pt benefit. [Table: see text]
Venetoclax-induced tumor lysis syndrome in acute myeloid leukemia: Real world experience.
Authors: Keruakous Amany , Saleem Rabia , Asch Adam Steven
Published: May 2020

e19542

Background: Venetoclax in combination with hypomethylating agents (HMAs) has become standard management for newly diagnosed older and unfit acute myeloid leukemia (AML) patients and an option for relapsed/refractory disease in cases unfit for aggressive therapy. Although venetoclax can lead to rapid tumor lysis syndrome (TLS) in chronic lymphocytic leukemia and therefore administrated in a weekly dose ramp-up to minimize toxicity, a modified dose ramp-up of venetoclax over 3–4 days in combination with HMAs has been investigated in AML trials without any reported cases of TLS (DiNardo et al, 2019). Notably, this trial prohibited azole fungal prophylaxis because of the known potentiation of venetoclax activity in that setting. Rare cases have been reported for venetoclax induced TLS in the context of CYP3A inhibition. This study presents cases with AML who developed TLS whilst receiving azacitidine/venetoclax combination. Notably, they shared similar pattern of disease progression. Methods: All AML patients who are unfit to receive induction chemotherapy, treated with venetoclax combination either upfront or in the salvage setting starting January 2019 until November 2019 were reviewed retrospectively. TLS was reported using Cairo-Bishop criteria (Cairo & Bishop, 2004), AML risk stratification and response evaluation by ELN-Leukemia NET. Results: We report fourteen cases treated with azacitidine/venetoclax combination, three cases developed venetoclax induced TLS despite following the TLS protocol per the phase 1b trial (administering allopurinol > 72 hours prior to initiation of venetoclax). All cases had intermediate to poor risk AML; all had WBCs < 25 k before starting venetoclax, 2 of 3 patients received CYP3A inhibitors for fungal prophylaxis. Disease burden, defined as per-cent of bone marrow involvement and peripheral circulating blasts, did not increase the risk of TLS. We observed TLS in newly diagnosed (n = 1) and in relapsed AML (n = 2). Also, with first initiation of venetoclax as well as with delayed onset and more prominent with azole fungal prophylaxis. All the cases of venetoclax induced TLS we observed, proved to be refractory to venetoclax combination after resumption of therapy. Conclusions: Venetoclax induced TLS is reportedly rare in AML. In our experience, TLS is more common in real world experience than has been previously reported. More prominent with azole fungal prophylaxis. Additionally, it appears to be associated with disease that proved ultimately refractory to venetoclax combination.
Survival trend of chronic lymphocytic leukemia and prognostic factors in the United States: An analysis of the National Cancer Database.
Authors: Dong Ning , Saeed Hayder , Gaballa Sameh , Shah Bijal D. , Coghill Anna , Isenalumhe Leidy Lismeri , Celeste Bello , Pinilla-Ibarz Javier , Chavez Julio C.
Published: May 2020

e20012

Background: The management of chronic lymphocytic leukemia (CLL) has evolved in the past decade, mainly due to the introduction of novel agents. The outcome of CLL in the general US population and the prognostic factors have not been studied. National Cancer Database (NCDB) includes about 70% of all malignancies in the US and provides a resource to address those questions. Methods: The most recent release of NCDB included CLL cases diagnosed in years 2004-2016. The following variables were included in Cox proportional hazard model for multivariate analysis: age, gender, race, ethnicity, comorbidity score, year of diagnosis, insurance, education, income, facility type, facility volume of CLL and distance to facility. Results: A total of 91309 CLL patients were identified. Median age of diagnosis was 70 years (IQR 61-79). Among the patients, 60.4% were male, 89.4% of patients were White, 7.7% were African American (AA) and 5.8% of patients had either Medicaid or no insurance. At the initial diagnosis, 31.5% of patients were started on treatment and the rest were under active surveillance. Transplant was performed in 0.18% of patients. The OS has improved in years 2010-2016 compared to 2004-2009 with median OS of 90.3 months (95% CI 87.3, .) and 83.6 months (95% CI 82.1-85.0), respectively and 5-year survival rate of 64.2% and 59.9%, respectively (p < 0.0001). Among the 1348 facilities, 16% saw less than 2 CLL patients per year. In the multivariate analysis, the following factors were associated with worse OS: older age, more comorbidities, AA, male gender, East South Central or South Atlantic area, no insurance or Medicaid, lower quartiles of education, and being treated in facilities with lower CLL-patient volume. Conclusions: CLL survival has improved in the past decade. Socioeconomic factors seem to impact survival and with the introduction of newer more expensive therapies, this discrepancy in survival might increase. Furthermore, CLL is a relatively rare malignancy and patients treated at lower-volume facilities had inferior survival. Special attention paid to patients with risk factors might improve outcome. [Table: see text]
Clinicopathological characteristics and outcome of plasmablastic lymphoma patients: A single-center retrospective analysis.
Authors: Dabrowska-Iwanicka Anna P , Romejko-Jarosinska Joanna , Targonski Lukasz , Kotarska Martyna , Swierkowska Monika , Paszkiewicz-Kozik Ewa , Wojciechowska-Lampka Elzbieta , Osiadacz Wlodzimierz , Tajer Joanna , Szymanski Marcin , Poplawska Lidia , Ostrowska Beata , Domanska-Czyz Katarzyna , Borawska Anna , Konecki Robert , Druzd-Sitek Agnieszka , Walewski Jan Andrzej
Published: May 2020

e20034

Background: Plasmablastic lymphoma (PBL) is a rare CD20-negative lymphoma with an aggressive clinical course and short median survival ranging from 9 to 32 months. It is often associated with HIV infection but it also affects immunocompetent patients. Due to the rare occurrence most data comes from small, retrospective series. Methods: This is a retrospective single-center analysis of PBL patients (pts) referred to MSCNRIO between 2003-2019. Diagnosis was established according to the WHO 2017 classification criteria. Kaplan–Meier method was used for calculating overall survival (OS) and progression-free-survival (PFS) and the log-rank test for comparisons. Univariate analysis of prognostic factors was carried out. Results: 24 pts with a diagnosis of PBL were included. The median age at diagnosis was 54 years (range 29-90). 15 pts (63%) were men. LDH was elevated in 10 pts (41%). Stage III or IV was reported in 21 (87.5%) pts, IPI score of 3-5 in 12 (50%) and ECOG performance status > 1 in 7 pts (29%). 20 pts (83.3%) had extranodal involvement, including oropharynx (n = 12), gastrointestinal tract (n = 1), bone marrow (n = 7), skeletal bone (n = 9), central nervous system (n = 3), skin and subcutaneous tissue (n = 2). Only 3 pts (13%) were infected by HIV, 2 had history of immunosuppressive therapy. Pathologically, all cases were negative for CD20 and positive for CD38 or CD138 expression. Ki67 > 90% was noted in 16 cases (66%). 11 pts received CHOP chemotherapy, 3 pts - thalidomide- and 4 pts - bortezomib-based regimens, 1 was treated with both agents. 4 pts received different protocols; 1 pt received no treatment. CR was observed in 8 pts (33%), PR in 6 (25%) and no response in 10 (42%). 2 pts received ASCT in the 1st remission. 17 pts (71%) experienced relapsed/progressive disease. 16 pts died: 11 from disease progression, 2 from other neoplasm. With a median follow-up of 20 months (range 2-122) median OS was 21 months and 2-year OS rate was 46% (95%C.I 27%, 65%). 2-year PFS rate was 37% (95% C.I. 17%, 57%), with median PFS 12 months (range 0.7-105). On univariate analysis there was a trend for correlation of high IPI with PFS; (95%C.I 0.99-1.03, P= 0.08). Achieving CR significantly correlated with better OS (HR 5; 95% C.I. 1.41-17; P= 0.01)) and PFS (HR 5.1, 95%C.I. 1.4, 18; P= 0.004). Conclusions: Our results confirm other reported data on PBL. Patients in our cohort shared typical clinical features but majority of them were immunocompetent. PBL prognosis remains poor despite incorporating novel agents into treatment and requires new therapeutic approaches.
The value of bendamustine dose and cycles, sIL-2R, and LDH in follicular lymphoma patients treated with bendamustine plus rituximab.
Authors: Jo Tatsuro , Matsuo Masatoshi , Taguchi Jun , Abe Kuniko , Shigematsu Kazuto
Published: May 2020

e20055

Background: Bendamustine plus rituximab therapy (BR) is one of the mainstays of therapy for follicular lymphoma (FL) patients (pts). Adverse events such as lymphopenia, neutropenia, and skin lesions sometimes prevent the completion of six cycles of BR. Till date, the bendamustine dose, treatment cycle of BR, and prognostic markers of FL response to BR have not been analyzed sufficiently. Methods: We retrospectively evaluated 56 FL pts treated with BR from January 2011toJanuary 2019 at our hospital; 19 pts and 37 pts received BR as first-line therapy and salvage therapy, respectively. Results: There was no statistical difference in the response rate, OS, and PFS between the first-line group and the salvage group. The table summarizes the survival analyses. Comparing the OS and PFS according to FL grades 1, 2, and 3 in all pts, there were significant differences in both OS (P = 0.0028) and PFS (P = 0.0058). Patients were divided into two groups based on a cutoff sIL-2R value of 682 U/mL; survival benefits were observed in the sIL-2R-low group in OS (P = 0.0226) and PFS (P = 0.0265). Similarly, on dividing the pts into two groups based on a cutoff LDH value of 225 U/L, survival benefits were observed in the LDH-low group in OS (P = 0.0375) and PFS (P = 0.0453). The LDH value was significantly high in pts with progression of disease within 24 months (POD24) compared to pts without POD24 (P = 0.0134). However, there was no statistical relationship between sIL-2R and POD24.The rate of treatment cycles ≧4 was 69%, and the mean number of treatment cycles was 4.3. Survival benefits were observed in pts who were treated for more than 3 cycles in OS (P = 0.0094) and PFS (P = 0.0103). The mean bendamustine dose was 78.5 mg/m2. Conclusions: Approximately 30% pts could not receive more than 3 cycles of BR, probably because of adverse events and preexisting bone marrow suppression with previous chemotherapy, suggesting that 90 mg/m2of bendamustine in BR may be excessive, especially in pts requiring salvage therapy. Our data suggest that 75−80 mg/m2of bendamustine may be appropriate. Our survival data also suggest that new treatment strategies may be needed for FL pts with high levels of sIL-2 ( >682 U/mL) and LDH ( >225 U/L) and grade 3 disease. [Table: see text]
Molecular predictors of central nervous system (CNS) recurrence in diffuse large B-cell lymphoma (DLBCL).
Authors: Waroich Jozal , Olszewski Adam J. , Kurt Habibe , Vatkevich John , Sturtevant Ashlee , Patel Nimesh , Ollila Thomas
Published: May 2020

e20082

Background: CNS recurrence is a devastating outcome after treatment of DLBCL. Clinical features poorly predict CNS recurrence risk or the need for prophylactic therapy. We examined whether specific mutational profiles in DLBCL may correlate with the risk of CNS recurrence. Methods: We evaluated DLBCL tumors from patients (pts) with either isolated CNS or systemic (without CNS) recurrence using a 592 gene next generation sequencing (NGS) assay (Illumina NextSeq platform, average coverage depth > 750x; Caris Life Sciences). 3 common molecular subtypes of DLBCL were identified using a simplified classification: (1) MCD subtype ( MYD88L265P or > 2 other mutations in CD79B, PIM1, ETV6, BTG1, TBL1XR1, or PRDM1) , (2) subtype characterized by TP53 mutations (± complex karyotype with multiple structural variants), and (3) GCB subtype characterized by ≥2 mutations in BCL2, CREBBP, EZH2, KMT2D, TNFRSF14, GNA13, MEF2B, or PTEN. We compared prevalence of these subtypes between our groups and unselected DLBCL datasets by Chapuy et al. ( Nat Med; n = 135) and Reddy et al. ( Cell, 2018; n = 1001). We additionally examined clinicopathologic data, including cell of origin, MYC, BCL2 and/or BCL6 rearrangements, and complex karyotype. Results: The study included 26 cases of DLBCL with CNS-only recurrence (n = 13) or systemic-only recurrence (n = 13). We observed no significant difference between these groups in any clinicopathologic characteristics, and no significant difference for mutations in any specific gene (using Fisher’s exact test adjusted for multiple testing). The MCD subtype was more frequent among pts with CNS recurrence (46%) versus systemic recurrence (31%), and was statistically significantly enriched in our CNS recurrence group compared with the unselected DLBCL datasets by Reddy (18%, P= 0.017) or Chapuy (19%, P= 0.030). In contrast, we observed no difference in CNS or systemic recurrence for the TP53 subtype (23% in both groups) or the GCB subtype (15% in both groups), and these proportions were not significantly different compared with the unselected DLBCL datasets ( P> 0.05). Conclusions: In-depth molecular classification of DLBCL using single nucleotide, structural chromosomal, and copy number variants is unfeasible in current clinical practice. Our data demonstrate that a clinically meaningful molecular signature predicting future CNS recurrence could be designed from standard NGS assays using a simplified classification. With further validation, this signature may prove useful for selecting pts for CNS-directed prophylaxis.