bluuebunny/crossref_metadata_2025_split huggingface dataset:
National trends in post-launch cancer prescription drug prices and the impact of generic entry, 2014-2020.
Authors: Rodin Danielle , Rosenthal Meredith B. , McGlave Claire , Bhaskar Anushka , To C , Conti Rena M. 
Published: June 2022

6598 Background: The high prices of branded ‘on patent’ cancer prescription drugs and the impact of competition on them is of importance to patients, physicians, payers and policymakers. The objective of this study is to quantify trends in the prices of all currently approved cancer drugs and to evaluate the impact of loss of exclusivity and generic entry on prices using national and contemporaneous data. Methods: Observational study of cancer drug prices from the IQVIA National Sales Perspectives from January 2014 to December 2020. The compound annual growth rate (CAGR) of drug prices was calculated for branded and generic drugs by therapeutic class (chemotherapy, targeted therapy, and supportive therapy). An event study empirical strategy and ordinary least squares regression was used to determine the relationship between the natural logarithm of prices and loss of exclusivity and generic entry. Results: The study cohort included 184 cancer drugs (37% chemotherapy, 51% targeted therapy, and 12% supportive therapy), of which 105 were always branded, 18 were always generic and 18 underwent loss of exclusivity and generic entry during the study period. Prices of branded chemotherapies and targeted therapies increased by 2.24% (0.79% CPI-adjusted) and 2.83% (1.07% CPI-adjusted) annually, whereas generics decreased by 12.63% (-14.14% CPI-adjusted) and 20.15% (-21.57% CPI-adjusted), respectively. Prices of branded supportive therapies decreased by 0.73% (-2.40% CPI-adjusted), while generics increased by 1.28% but decreased with CPI-adjustment (-0.45). Loss of exclusivity and generic entry was associated with statistically significant decreases in generic drug prices, but increases in branded drug prices after CPI-adjustment; these effects are concentrated in chemotherapies and targeted therapies. Conclusions: We found that cancer drug prices increased, after adjusting for inflation, particularly among branded chemotherapies and targeted therapies. Generic entry mitigates these price increases, but only a handful of cancer drugs experienced competition in the study period. Drug prices are key determinants of cancer-related spending, and many cancer patients remain underinsured. Although this data reflects net prices before discounts to providers and pharmacies, patient out-of-pocket costs are based on the list price. Our findings are critical to informing current efforts to improve cancer treatment affordability.
Cost-effectiveness of adjuvant chemotherapy for patients with high-risk stage II and stage III colon cancer in South Africa.
Authors: Pumpalova Yoanna S , Rogers Alexandra M. , Tan Sarah Xinhui , Herbst Candice-Lee , Ruff Paul , Neugut Alfred I. , Hur Chin 
Published: June 2022

6599 Background: Colon cancer (CC) incidence is rising globally, and case fatality rates are greatest in low-income settings, such as South Africa (SA). Adjuvant chemotherapy is standard of care for high-risk stage II and stage III CC in the US. We evaluated the cost-effectiveness of adjuvant chemotherapy for CC in SA public hospitals. Methods: We developed a decision-analytic Markov model comparing lifetime costs and outcomes for 60-year-old high-risk stage II and stage III CC patients treated in a SA public hospital with no adjuvant chemotherapy, versus: capecitabine and oxaliplatin (CAPOX) for 3 or 6 months or capecitabine for 6 months. High-risk stage II was defined as ≥1 of: T4 disease; poorly differentiated tumor; lymphovascular/perineural invasion; <12 lymph nodes dissected, bowel obstruction/perforation. Transition probabilities were derived from clinical trials estimating toxicity, disease recurrence, and survival. Costs from a SA societal perspective and utility estimates were obtained from literature and local expert opinion. The primary outcome was the incremental cost-effectiveness ratio (ICER) in international dollars (I$) per disability-adjusted life year (DALY) averted, with a willingness-to-pay (WTP) threshold equal to 2021 GDP/capita of SA (I$13,764). Results: CAPOX for 3 months was the cost-effective strategy for stage III CC at a lifetime cost of I$5,284 and 5.55 DALYs averted, compared to no adjuvant treatment. All other strategies were absolutely dominated. For high-risk stage II CC, CAPOX for 3 months was the cost-effective strategy (ICER = I$711/DALY averted). No adjuvant chemotherapy was on the efficiency frontier, with a lower lifetime cost, but no DALYs averted. The results of one-way deterministic sensitivity analyses showed that the model is most sensitive to CC recurrence rate. In a probabilistic sensitivity analysis, CAPOX for 3 months was optimal in 88% of iterations for high-risk stage II CC and 79% of iterations for stage III CC. Conclusions: CAPOX for 3 months is the cost-effective adjuvant treatment for high-risk stage II and stage III CC in SA public hospitals. This strategy offers the highest quality of life benefit for the lowest cost and is well within the WTP threshold for SA. The optimal strategy in other settings will vary according to local WTP thresholds. Base case estimates of cost-effectiveness, in order of cost. [Table: see text]
A phase II trial of a chemotherapy-free combination of ponatinib and blinatumomab in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL).
Authors: Short Nicholas James , Kantarjian Hagop M. , Konopleva Marina , Bravo Guillermo Montalban , Ravandi Farhad , Jain Nitin , Kadia Tapan M. , Alvarado Valero Yesid , Chien Kelly Sharon , Daver Naval Guastad , Macaron Walid , Sasaki Koji , Thankachan Jennifer , Delumpa Ricardo , Mayor Ejiroghene , Deen Wuliamatu , Loiselle Christopher , Kwari Monica , Garris Rebecca , Jabbour Elias 
Published: June 2022

7009 Background: Ponatinib and blinatumomab are highly active in Ph+ ALL. A chemotherapy-free combination of these agents may lead to durable remissions and reduce the need for stem cell transplant (SCT) in first remission. Methods: In this phase II study, adults with newly diagnosed (ND) Ph+ ALL, relapsed/refractory (R/R) Ph+ ALL, or CML in lymphoid blast phase (CML-LBP) received up to 5 cycles of blinatumomab. Ponatinib 30mg daily was given during cycle 1 and decreased to 15mg daily once a complete molecular response (CMR) was achieved. After completion of blinatumomab, ponatinib was continued for at least 5 years. All patients (pts) received 12 doses of prophylactic IT chemotherapy. Results: Between 2/2018 and 1/2022, 55 pts were treated (35 ND, 14 R/R and 6 CML-LBP). Baseline characteristics and responses are shown in Table. Among 23 pts with ND Ph+ ALL evaluable for response, 22 (96%) achieved CR/CRi; 1 pt had early death due to myelosuppression from prior chemotherapy. Among 13 evaluable pts with R/R Ph+ ALL, 12 (92%) achieved CR/CRi. The CMR rates for the ND, R/R and CML-LBP cohorts were 64%, 71%, and 17% after cycle 1 and were 85%, 79%, and 33% overall, respectively. In the ND cohort, 4/17 evaluable pts (24%) achieved CMR in the peripheral blood within 1 week, and 9/15 (60%) within 2 weeks. The median follow-up is 11 months (range, 1-46+ months). Among the 35 pts in the ND cohort, 33 pts (94%) are alive and in continuous remission. Only 1 pt in the ND underwent SCT in first remission (due to persistent MRD positivity), and no relapses have been observed. The 2-year EFS and OS rates in the ND cohort are 93%. Among the 13 responding pts in the R/R cohort, 6 (46%) underwent SCT. The 2-year EFS and OS rates for the R/R cohort are 42% and 61%, and for the CML-LBP cohort are 33% and 60%, respectively. Most side effects were grade 1-2 and were consistent with the known toxicity profile of the two agents individually. Two pts discontinued ponatinib due to toxicity (1 due to stroke and 1 due to DVT). One pt discontinued blinatumomab due to recurrent neurotoxicity. Conclusions: The chemotherapy-free combination of ponatinib and blinatumomab was safe and effective in Ph+ ALL and CML-LBP. Longer follow-up continues to demonstrate durable remissions, particularly in ND Ph+ ALL, even without SCT in first remission. Clinical trial information: NCT03263572. [Table: see text]
Comparison of demographics, disease characteristics, and outcomes between African American patients and White patients with myelodysplastic syndrome: A population-based study.
Authors: Lesegretain Arnaud , Laadem Abderrahmane , Fell Geoffrey , Fathi Amir Tahmasb 
Published: June 2022

7051 Background: Myelodysplastic syndrome (MDS) consists of a heterogeneous group of clonal myeloid neoplasms, classified as a malignancy since 2001. Previous studies have described inferior outcomes for African Americans (AA) versus Whites (W) in several solid tumors and hematological malignancies, including AML. We performed an analysis of the Survival, Epidemiology, and End Results (SEER) cancer registry to analyze baseline characteristics and various outcomes. Methods: Using SEER (18 Registries, 2000-2018, Nov 2020 submission), we included 37,564 patients (pts) with microscopically confirmed MDS, age > = 20, diagnosed between 2000-2013 based on ICO-O3 codes. MDS sub-types were grouped into low, intermediate, and high-risk disease. We compared baseline characteristics, mortality rates per attributed cause of death (COD) and overall survival (OS). Multivariate Cox regression and Propensity Score analyses were conducted to reduce effect of confounding due to imbalance in baseline covariates. Results: We included 34,543 W (92%) and 3021 AA (8%) pts; There were more males (58%) among W vs AA (49%). At diagnosis the median age was 71 and 76 in AA and W subjects, respectively. Low and high risk MDS comprised 22.8% and 14.5% of cases among AA and 21.5% and 16.3% among W pts, respectively. 66.8% of AA were living in large metropolitan areas vs 60.2% for W pts. mOS was 33 months for AA and 26 months for W; HR for OS comparing W vs AA using a univariate Cox PH model was: 0. 79 (0.76- 0.82), p < 0.001. In a multivariate Cox-PH model, HR for OS after adjusting for sex, age at diagnosis, histology, urban-rural continuum, income group was: 0.90 (95%CI 0.86-0.94), p < 0.001. HRs after stratified cox PH model and propensity score matching model for age, sex, histology and income group were 0.92 (0.88-0.96), p < 0.001 and 0.93(0.88-0.98), p = 0.01 respectively. Analysis by histology shows statistically significant association between race and OS for refractory anemia and MDS-unclassifiable while not significant for refractory anemia with ringed sideroblasts, refractory anemia with excess blasts and MDS with del(5q). Incidence rate ratio for AA vs W for death attributed to the two most frequent CODs were: MDS/Leukemia: 0.74 (0.69-0.81, p < 0.001); CVD: 1.07 (0.94-1.21, ns). Conclusions: In this large study of MDS cases reported to the SEER registry, we observed differences in age, sex, disease subtype, socio-economic factors, mortality rate per attributed COD, survival outcomes between AA and W. The finding of AA having better OS outcomes than W pts is unexpected and needs to be further investigated, specifically the contribution of the less well-defined low-grade risk forms of MDS. Although caution in the interpretation is necessary due to multiple limitations inherent to the SEER dataset, this data does raise intriguing questions for future study.
Lisocabtagene maraleucel (liso-cel) as second-line (2L) therapy for R/R large B-cell lymphoma (LBCL) in patients (pt) not intended for hematopoietic stem cell transplantation (HSCT): Primary analysis from the phase 2 PILOT study.
Authors: Sehgal Alison , Hoda Daanish , Riedell Peter A. , Ghosh Nilanjan , Hamadani Mehdi , Hildebrandt Gerhard , Godwin John E. , Reagan Patrick Michael , Wagner-Johnston Nina D. , Essell James , Nath Rajneesh , Solomon Scott R. , Champion Rebecca , Licitra Edward , Fanning Suzanne , Gupta Neel K. , Dubowy Ronald L. , D’Andrea Aleco , Wang Lei , Gordon Leo I. 
Published: June 2022

7062 Background: Pts with R/R LBCL after first-line (1L) treatment (tx) who are unable to undergo high-dose chemotherapy (HDCT) and HSCT have poor outcomes and limited tx options. PILOT (NCT03483103) evaluated liso-cel, an autologous, CD19-directed chimeric antigen receptor (CAR) T cell product, as 2L tx in pts with R/R LBCL not intended for HSCT. Methods: Eligible pts were adults with R/R LBCL after 1L tx who were not deemed candidates for HDCT and HSCT by their physician and met ≥ 1 frailty criteria: age ≥ 70 yr, ECOG PS = 2, DLCO ≤ 60%, LVEF < 50%, CrCl < 60 mL/min, or ALT/AST > 2 × ULN. Bridging tx was allowed. Pts received lymphodepletion with cyclophosphamide and fludarabine, followed 2–7 days later by liso-cel at a target dose of 100 × 106 CAR+ T cells. Cytokine release syndrome (CRS) was graded per Lee 2014 criteria and neurological events (NE) per NCI CTCAE, version 4.03. Primary endpoint was ORR per independent review committee (IRC); all pts had ≥ 6 mo follow-up (f/u) from first response. Results: Of 74 pts leukapheresed, 61 received liso-cel and 1 received nonconforming product. Common reasons for pre-infusion dropout included death and loss of eligibility (5 each). For liso-cel–treated pts, median age was 74 yr (range, 53–84; 79% ≥ 70 yr) and 69%, 26%, and 5% met 1, 2, and 3 frailty criteria, respectively; 26% had ECOG PS = 2 and 44% had HCT-CI score ≥ 3. After 1L tx, 54% were chemotherapy refractory, 21% relapsed ≤ 12 mo, and 25% relapsed > 12 mo; 51% of pts received bridging chemotherapy. Median (range) on-study f/u was 12.3 mo (1.2–26.5). ORR and CR rate was 80% and 54%, respectively. Median DOR and PFS was 12.1 mo and 9.0 mo, respectively. Median OS has not been reached (Table). Most frequent tx-emergent AEs (TEAE) were neutropenia (51%), fatigue (39%), and CRS (38%), with grade (gr) 3 CRS in 1 pt (2%) and no gr 4/5 CRS. Any-grade NEs were seen in 31%, gr 3 in 5% (n = 3), and no gr 4/5 NEs; 7% received tocilizumab, 3% corticosteroids, and 20% both for tx of CRS/NEs. Overall, gr ≥ 3 TEAEs occurred in 79%, with gr 5 in 2 pts (both due to COVID-19). Two pts (3%) had gr 3/4 infections and 15 (25%) had gr ≥3 neutropenia at Day 29. Conclusions: In the PILOT study, liso-cel as 2L tx in pts with LBCL who met ≥ 1 frailty criteria and for whom HSCT was not intended demonstrated substantial and durable overall and complete responses, with no new safety concerns. Clinical trial information: NCT03483103. [Table: see text]
Subgroup analysis in RE-MIND2, an observational, retrospective cohort study of tafasitamab plus lenalidomide versus systemic therapies in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL).
Authors: Nowakowski Grzegorz S. , Yoon Dok Hyun , Joffe Erel , Zinzani Pier Luigi , Sabatelli Lorenzo , Waltl Eva E. , Alvero Carmelita G. , Hess Georg , Riedell Peter A. , Kim Kibum , Brixner Diana , Salles Gilles A. 
Published: June 2022

7560 Background: Tafasitamab (tafa) + lenalidomide (LEN) demonstrated efficacy in adult patients (pts) with R/R DLBCL ineligible for autologous stem-cell transplant in the pivotal Phase II study L-MIND (NCT02399085) and received accelerated approval in the United States in 2020 and conditional marketing authorization in Europe and Canada in 2021 in this setting. RE-MIND2 (NCT04697160), an observational, retrospective cohort study, compared pt outcomes from L-MIND with matched pt cohorts treated with other NCCN/ESMO recommended therapies. Methods: Methodology for RE-MIND2 has been presented previously. Hypothesis-generating analyses were conducted for pt subgroups of number of extranodal sites (ENS) (0–1 vs ≥2) and elevated lactate dehydrogenase (LDH) (yes vs no) in matched cohorts of pts receiving tafa + LEN vs systemic therapies pooled (STP), polatuzumab vedotin + bendamustine + rituximab (pola-BR), rituximab + LEN (R2), and CD19 CAR-T therapies (CAR-T). The primary endpoint was overall survival (OS). Results: Of 3,454 pts enrolled, 961, 106, 106, and 149 were treated with STP, pola-BR, R2, and CAR-T, resulting in 76, 24, 33, and 37 matched pairs for pts receiving tafa + LEN, respectively. Hazard ratios (HR) for OS show a trend toward favoring tafa + LEN in most pt subgroups (Table). Conclusion: These analyses suggest that tafa + LEN may be associated with improved OS vs selected systemic therapies for certain pts with high-risk disease and may further inform physicians’ treatment choices for pts with R/R DLBCL. These analyses are not powered for statistical comparison; small sample sizes in some subgroups result in wide confidence intervals (CI) and so results must be interpreted with caution. Data for other treatment cohorts, pt subgroups, and endpoints will be presented. Funding: MorphoSys AG. Clinical trial information: NCT04697160. [Table: see text]
Cost effectiveness of polatuzumab vedotin in combination with chemoimmunotherapy (Pola-R-CHP) in previously untreated diffuse large B-cell lymphoma.
Authors: Kambhampati Swetha , Saumoy Monica , Pak Stacy , Budde L Elizabeth , Mei Matthew Genyeh , Popplewell Leslie , Wen Yi-Ping , Forman Stephen J. , Kwak Larry W. , Rosen Steven T. , Herrera Alex Francisco , Thiruvengadam Nikhil 
Published: June 2022

7568 Background: In patients with treatment naive diffuse large B-cell lymphoma (DLBCL), the POLARIX study demonstrated a 6.5% improvement in the 2-year (yr) progression-free survival (PFS) with no difference in overall survival or safety using polatuzumab vedotin + R-CHP compared to standard RCHOP. We evaluated the cost effectiveness of pola-R-CHP for DLBCL. Methods: We modeled a hypothetical cohort of US adults (mean age, 58 yrs) with treatment naïve DLBCL by developing a Markov model with a 1-month cycle and 20-yr horizon. The cost-effectiveness of two strategies were directly compared (pola-R-CHP, RCHOP) using a range of plausible long-term outcomes. A patient with DLBCL in remission after treatment could develop subsequent progression or relapse, death, or alternative toxicity. Progression rates and overall survival were estimated from POLARIX study. Outcome measures were reported in incremental cost-effectiveness ratios (ICERs), with a willingness-to-pay (WTP) threshold of $150,000/quality-adjusted life-yr (QALY). Results: Assuming a 5-yr PFS of 69.6% with pola-R-CHP and 62.6% with RCHOP, pola-R-CHP was more effective (0.81 incremental QALYs) but more costly ($66,218) and was cost-effective at a WTP of 150,000 (ICER $82,220/QALY). Its cost effectiveness was highly dependent on the 5-yr PFS of pola-R-CHP with it no longer being cost effective if the 5-yr PFS was < 65%. One way sensitivity analysis demonstrated that pola-R-CHP is cost effective up to a cost of $270,506 at a WTP of $150,000. Probabilistic sensitivity analysis was derived from performing 10,000 Monte-Carlo model iterations and demonstrated that pola-R-CHP was the cost-effective strategy in 61.3% of iterations with RCHOP being cost-effective in 38.6% of iterations at a WTP of $150,000. Conclusions: If the absolute benefit in PFS is maintained over time, frontline pola-R-CHP for treatment of DLBCL would be cost effective at its current cost when compared to RCHOP at a WTP of $150,000/QALY. However, its cost effectiveness is highly sensitive to changes in long-term PFS and the cost of pola-R-CHP. If pola-R-CHP is adopted as frontline therapy for the 29,108 incident cases of DLBCL annually in the US, this will lead to an additional 1.8 billion dollars in healthcare expenditures. This highlights the importance of decreasing the cost of pola-R-CHP and identifying sub-populations that derive the highest benefit from it.[Table: see text]
Therapy for patients with POD24 follicular lymphoma: Treatment patterns and outcomes from the Lymphoma Epidemiology of Outcomes (LEO) Consortium.
Authors: Casulo Carla , Larson Melissa C. , Day Jonathan R , Habermann Thomas Matthew , Lossos Izidore S. , Wang Yucai , Nastoupil Loretta J. , Strouse Christopher , Chihara Dai , Martin Peter , Cohen Jonathon Brett , Kahl Brad S. , Ruan Jia , Burack Walter Richard , Koff Jean Louise , Friedberg Jonathan W. , Cerhan James Robert , Flowers Christopher , Link Brian K. , Maurer Matthew J. 
Published: June 2022

7573 Background: While most patients (pts) with follicular lymphoma (FL) usually have favorable outcomes, those with refractory disease after first-line anti-CD20 based immunochemotherapy (IC), or progression within 24 months of diagnosis (POD24) have higher risk of premature death. There are no standard approaches for treating this vulnerable group and studies testing novel agents are ongoing in this setting. We sought to investigate clinical practice treatment choices and efficacy for pts with POD24 that align with eligibility criteria for the randomized SWOG1608 which compares IC with novel agents in this population. Methods: This was a multicenter observational cohort study from the LEO Consortium. Eligible pts had grade 1-3a FL diagnosed between 1/1/2002 and 2/1/2019, and initiated therapy after POD24 to first-line bendamustine or CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) based IC. Observation, radiotherapy, or rituximab monotherapy were permitted prior to IC and pts with transformation prior to the subsequent therapy after IC were excluded as per S1608. Outcomes of interest were overall and complete response rate (ORR/CR), progression-free survival (PFS), and overall survival (OS). Results: We identified 196 eligible pts with early progression to IC (39% antiCD20 Benda; 61% antiCD20 CHOP) who received subsequent therapy. Median age at post IC treatment was 57 years, 78% grade 1-2 FL. Treatments for pts with POD24 included CHOP- or Benda-based in 31%, salvage/hematopoietic stem cell transplant (HSCT) in 27%, novel therapies in 10% (including phosphatidylinositol 3-kinase inhibitors), antiCD20 monotherapy in 9%, and lenalidomide-based treatment in 8% (table); 21% of pts were treated on clinical trials. Across all treatments, ORR (CR) was 63% (37%) (95% CI: 55-70). At a median follow up of 6.2 years, 2 year PFS was 22% (95% CI: 17%-29%) and 5 year OS was 71% (95% CI: 65-79). Outcomes by regimen are shown in the table. Conclusions: Pts with FL experiencing POD24 following first-line IC are treated heterogeneously, with many pts still receiving IC as subsequent therapy. Despite modest CR rates and low 2-year PFS, 5-year OS appear to be improving compared to historical outcomes. This supports the ongoing need to investigate novel treatments in this population. [Table: see text]