bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in low-value oncology care during the COVID-19 pandemic.
Authors: Parikh Ravi Bharat , Civelek Yasin , Ozluk Pelin , Debono David Joseph , Fisch Michael Jordan , Sylwestrzak Gosia , Bekelman Justin E. , Schwartz Aaron L
Published: June 2022

6594

Background: Low-value services, which provide minimal patient benefit while entailing costs and risks, are prevalent in cancer care. Shifts in cancer care delivery during the COVID-19 pandemic to minimize exposure provided opportunities for health systems and clinicians to prioritize higher-value over low-value oncology services. Methods: In this retrospective cohort study, we investigated the association between the COVID-19 pandemic period and low-value cancer care practices using administrative claims from the HealthCore Integrated Research Environment, consisting of ̃65 million members managed by 14 health plans across the US. We identified commercial or Medicare Advantage members diagnosed with breast, colorectal, or lung cancer between January 2015 and March 2021. Low-value cancer care practices were identified from peer-reviewed medical literature, including ASCO and ASTRO Choosing Wisely campaigns and evidence-based pathways. Five low-value practices were studied: (1) conventional fractionation instead of hypofractionation for early-stage breast cancer; (2) off-pathway systemic therapy; (3) non-guideline-based antiemetic use for minimal-, low-, or moderate-to-high-risk chemotherapies; (4) Positron Emission Tomography/Computed Tomography (PET/CT) instead of conventional CT for staging; and (5) aggressive end-of-life care (chemotherapy ≤14 days, multiple emergency department visits ≤30 days, ICU utilization ≤30 days, hospice initiation ≤3 days, and/or no hospice before death). We used linear probability models to evaluate the association between the COVID-19 period (March to December 2020) and the 5 outcomes, adjusting for patient, facility, geographic and temporal characteristics. Results: Among 204,581 members (mean age 63.1, 139,488 [68.1%] female), 83,593 (40.8%) had breast cancer, 56,373 (27.5%) had colon cancer, and 64,615 (31.5%) had lung cancer. Rates of low-value care were similar in pre-COVID vs. COVID periods: conventional radiotherapy: 22.1% vs. 9.4%; off-pathway systemic therapy: 36.7% vs. 43.2%; non-guideline-based antiemetics: 61.2% vs. 58.1%; PET/CT imaging: 39.9% vs. 41.3%; aggressive end-of-life care: 75.8% vs. 73.3%. In adjusted analyses, the COVID-19 period was associated with no changes in off-pathway therapy (adjusted percentage point difference [aPPD] 0.82, SD 0.08, p = 0.33), PET/CT imaging (aPPD 0.10, SD 0.005, p = 0.83), and aggressive end-of-life care (aPPD 2.71, SD 0.02, p = 0.16). Small changes in conventional radiotherapy (aPPD 3.93, SD 0.01, p < 0.01) and non-guideline-based antiemetics (aPPD -3.62, SD 0.006, p < 0.01), were noted. Conclusions: The shock of the COVID-19 pandemic did not meaningfully change several metrics of low-value cancer care. Broader changes to payment and incentive design should be considered to turn the tide toward higher-value cancer care.
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]
Impact of sex on outcomes in patients with hairy cell leukemia (HCL): An HCL Patient Data Registry (PDR) analysis.
Authors: Epperla Narendranath , Zhao Qiuhong , Anghelina Mirela , Neal Jasmine , Blachly James Stewart , Rogers Kerry Anne , Lozanski Gerard , Oakes Christopher , Bhat Seema , Banerji Versha , Zent Clive , Grever Michael R. , Andritsos Leslie Ann
Published: June 2022

7577

Background: HCL is a rare indolent leukemia that is more common in men, with a 4:1 male predominance. To date, no studies have characterized the potential difference in outcomes of HCL between male and female patients. Hence, we sought to evaluate the outcomes of female HCL patients using the HCL-PDR. Methods: The HCL Foundation sponsored the development of HCL-PDR to characterize the clinical features and outcomes of this rare leukemia. HCL-PDR is an international multicenter PDR that includes patient, disease and treatment information abstracted from medical records. Adult patients enrolled in the HCL-PDR were included in the study. Female patients with HCL were the study population, with males as the comparator. The primary endpoint was the time to next treatment (TTNT) in females compared to males. Secondary endpoints included response rates (RR) and predictors of TTNT. Responses were categorized as: complete response (CR) including CR/CRu (CR unconfirmed)/HR (hematologic response), and partial response (PR), which included PR/PRu (PR unconfirmed)/pHR (partial HR). CRu was defined as no disease in bone marrow (BM) without available blood counts and HR as blood counts meeting criteria for HR, but no available BM. Cox proportional hazard models were used to estimate the hazard ratios for TTNT risk. Results: 357 patients were included: 265 males and 92 females. Table shows baseline characteristics stratified by sex. Among the patients who had disease status assessed after first treatment (n=224, males 169 and females 55), there was no significant difference in RR. However, females had significantly longer median TTNT (17.6 years) relative to males (8 years, HR 0.54, 95% CI 0.32-0.91, p=0.02) that remained significant after adjusting for other variables (RR and BRAF mutation) in multivariable analysis (HR 0.32, 95% CI 0.11-0.97, p=0.04). Factors predictive of longer TTNT include female sex and CR (HR.0.26, 95% CI 0.11-0.57, p=0.001). Conclusions: This is the first study to date reporting the clinical characteristics and outcomes in female HCL patients. The significantly longer TTNT in females compared to males may be related to factors such as underlying molecular features or hormonal influences. This finding needs to be explored further. [Table: see text]
Comparative effectiveness of teclistamab versus real-world treatments for patients with triple-class exposed (TCE), relapsed/refractory multiple myeloma (RRMM).
Authors: Krishnan Amrita Y. , Nooka Ajay K. , Chari Ajai , Garfall Alfred L. , Martin Thomas G. , Nair Sandhya , Lin Xiwu , Qi Keqin , Londhe Anil , Pei Lixia , Ammann Eric , Kobos Rachel , Smit Jennifer , Parekh Trilok V. , Slavcev Mary , Usmani Saad Zafar
Published: June 2022

8036

Background: Teclistamab is a B-cell maturation antigen × CD3 bispecific antibody currently being evaluated in MajesTEC-1 (NCT04557098), an open-label, single-arm, phase 1/2 trial in patients with RRMM who had received ≥3 prior lines of therapy (LOT) and were TCE to an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. Given the absence of a control arm in MajesTEC-1, we assessed the comparative effectiveness of teclistamab versus treatment regimens using an external control arm from a real-world database. Methods: An external control arm for MajesTEC-1 was created from eligible patients in the nationwide de-identified electronic health record-derived Flatiron Health multiple myeloma cohort database who started a new line of therapy (physician’s choice) following triple-class exposure between January 2011 and August 2021, received ≥3 prior LOT, and satisfied key MajesTEC-1 eligibility criteria. Individual patient data from MajesTEC-1 included patients who received teclistamab (1.5 mg/kg weekly) at a clinical cutoff of Sep 7, 2021. Inverse probability of treatment weighting (IPTW) was used to adjust for imbalances in baseline covariates of prognostic significance: refractory status, progression on last LOT, cytogenetic risk, International Staging System stage, number of prior LOT, time since diagnosis, age, and hemoglobin. Outcomes of interest included progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS); these outcomes were analyzed as time-to-event data using IPTW adjusted Kaplan-Meier estimates and a weighted Cox proportional hazards model. Several sensitivity analyses were conducted. Results: After IPTW, baseline characteristics were comparable between the 2 cohorts. Patients treated with teclistamab had improved PFS (hazard ratio [HR] 0.43; 95% confidence interval [CI] 0.32–0.59; P< 0.0001), TTNT (HR 0.42; 95% CI 0.31–0.58; P< 0.0001), and OS (HR 0.73; 95% CI 0.48–1.09; P= 0.13) versus assessed real-world treatments. Results were similar for all sensitivity analyses. Conclusions: Teclistamab showed improved effectiveness for PFS, TTNT, and OS, compared with real-world treatments used in patients with TCE RRMM who received ≥3 prior LOT. These findings highlight the therapeutic potential of teclistamab in patients with RRMM who have limited treatment options.
Factors associated with dose adjustment for the bortezomib, lenalidomide, dexamethasone regimen among patients with newly diagnosed multiple myeloma.
Authors: Ran Tao , Medhekar Rohan , Fu Alex Z. , Patel Sharmila , Kaila Shuchita
Published: June 2022

8039

Background: VRd (bortezomib/lenalidomide/dexamethasone) has become one of the established treatment regimens in the US for multiple myeloma (MM). Due to toxicities, dose adjustments are often required for VRd. This real-world study described the patient characteristics and factors associated with dose adjustment among MM patients treated with VRd as first line (1L) therapy. Methods: Adult MM patients treated with 1L VRd were selected from the Optum Clinformatics database (Nov 1, 2015-Sep 30, 2020). Patient characteristics were evaluated during a 6-month baseline period. Dose adjustments were defined based on lenalidomide (len) dose received during 1L. Receipt of > 15mg len was categorized as VRd regular, ≤15mg len as VRd lite, and initial len dose > 15mg reduced to ≤15 mg over treatment period as VRd reduced. Baseline factors associated with different VRd dose categories were studied using multinomial logistic regression. Results: Among the 1497 patients identified, the mean (SD) age was 69 (9.5) years (52% ≥70), 51% were male, 59% were White, 37% were frail, and 67% with Medicare. Baseline Charlson Comorbidity Index was 4.2, with hypertension (70%), hyperlipidemia (56%), renal impairment (26%), and CVD (25%) being the most prevalent comorbidities. Over half of the patients received an adjusted dose, VRd lite (33%) and VRd reduced (22%). Overall, for patients treated with 1L VRd, median follow-up was 16.2 months; median duration of 1L was 4.9 months (among those with confirmed end of therapy); and median TTNT was 14.5 months. Compared to VRd regular, use of VRd lite was over 6 times more likely to be associated with patients ≥75 years of age, about 2 times more likely to be associated with females, and about 40% less likely to be associated with commercial insurance vs. Medicare; VRd reduced was 1.3 times more likely to be associated with females, and 1.5 times more likely to be associated with frail patients (table). No differences were observed among different races. Conclusions: Over half of the MM patients treated with 1L VRd in the real-world were > 70 years of age and over one-third were frail. A large proportion of patients received a modified dose of VRd. Receipt of VRd lite dose was highly associated with older age (≥75 years), and receipt of VRd reduced dose was associated with frailty. These dose adjustments may potentially result in reduced efficacy of the VRd regimen in the real-world relative to controlled clinical trials, which needs to be assessed in future studies. [Table: see text]
Clinicopathological characteristics of high-risk multiple myeloma in Hispanic versus non-Hispanic patients in central California.
Authors: Hwang Andrew , Doornenbal Jason , Park Daniel , Bal Inderpreet , Bukari Mohammed SANI , Yan Yueqi , Abdulhaq Haifaa
Published: June 2022

8056

Background: Roughly 37% of Multiple Myeloma (MM) patients in the U.S. are non-white minorities. Advanced stage at diagnosis and specific cytogenetic abnormalities are associated with high-risk disease and poor prognosis. Few studies evaluated these risk factors in ethnic minorities. To further investigate, we analyzed ethnic variations in characteristics and outcomes of high-risk MM patients who were treated at our institution in Fresno, CA (49.6% Hispanic population). Methods: Patients diagnosed with high-risk MM at Community Medical Centers from 1-1-2011 to 12-31-2020 were included. High risk was defined by Mayo Clinic mSMART 3.0 classification. Demographic and disease-relevant information were collected. Cytogenetics, R ISS stage, 1st line treatment (doublet vs triplet), and treatment response (IMWG response criteria) were evaluated. Hispanic and non Hispanic comparisons were made by Fisher’s exact test where appropriate. Progression Free Survival (PFS) and Overall Survival (OS) were evaluated by Kaplan-Meier estimates and compared via log-rank test. Univariate cox proportional hazard model for survival was used to examine the association of variables with mortality risk after 1st line therapy. Results: 147 MM patients were screened. 42 high risk patients were identified: 11 (26%) Hispanic, 31 (74%) non Hispanic (22 white, 8 African American, 1 East Indian). Median age at diagnosis was 65. 26 (61%) were females. 25 (59%) were R ISS stage 3. Hispanic vs non Hispanic median income was $46119 vs $65080 (p=0.035). 6 Hispanics had Medi-Cal insurance vs 2 non-Hispanics (54.6% vs 6.5%, p=0.003). More Hispanics had Lambda light chain disease (73% vs 26%; p=0.01). 13 non Hispanics had del 17p vs 0 Hispanics (p=0.009). 40/42 patients (95%) received triplet therapy. 4 Hispanics received ASCT vs 9 non Hispanics (40% vs 33.3%, p=0.716). Hispanics and non Hispanics did not have significantly different treatment responses per IMWG criteria (p=0.799). No significant difference in PFS was seen between Hispanics and non Hispanics (805 vs 793 days; p=0.089); OS was better in Hispanics (1062 days vs 453 days; p=0.008). Per univariate cox proportional Hazard model, female sex (HR 4.34) and age (HR 1.05) were associated with higher mortality while Hispanic ethnicity was associated with lower mortality (HR 0.19). Conclusions: Hispanic and non Hispanic high risk MM patients differed significantly in median income, insurance, and del 17p incidence. These did not translate to a difference in 1st line therapy or treatment response. OS in our study is higher in Hispanic high-risk MM patients compared to other ethnicities and warrants further investigation. [Table: see text]
PD-L1 score as a prognostic biomarker in Asian patients with early-stage, EGFR-mutated lung cancer.
Authors: Saw Stephanie , Lai Gillianne , Tan Aaron C. , Zhou Siqin , Ang Mei-Kim , Lim Wan-Teck , Kanesvaran Ravindran , Tan Wan Ling , Rajasekaran Tanujaa , Chan Johan , Teh Yi Lin , Ong Boon-Hean , Takano Angela M. , Tan Eng Huat , Tan Sze Huey , Tan Daniel Shao-Weng
Published: June 2022

8527

Background: Adjuvant Atezolizumab was recently approved in stage II-IIIA non-small cell lung cancer (NSCLC) with PD-L1 ≥1%. However, disease-free survival (DFS) benefit was mainly driven by PD-L1 ≥50% and among EGFR-mutated subgroup, atezolizumab did not demonstrate DFS benefit when PD-L1 0% patients were included. We sought to determine the prognostic value of PD-L1 score in early-stage EGFR-mutated NSCLC. Methods: Consecutive patients with Stage IA-IIIA NSCLC diagnosed 1/1/2010 – 31/12/2019 who underwent curative surgery at National Cancer Centre Singapore with evaluable EGFR and PD-L1 status were included. Co-primary endpoints were 2-year DFS and 5-year overall survival (OS) by Kaplan-Meier method. Results: 455 patients were included (267 EGFR-mutant; 188 EGFR-wildtype). Median age at diagnosis was 65 years, 52.3% (238/455) were males and 62.9% (286/455) were never-smokers. Adenocarcinomas comprised 92.1% (419/455) and 92.5% (421/455) had R0 resection. Stage IA comprised 42.4% (193/455), Stage IB 23.1% (105/455), Stage II 15.8% (72/455) and Stage IIIA 18.7% (85/455). Among EGFR-mutant, 45.3% (121/267) were Ex19del and 41.9% (112/267) were L858R. PD-L1 ≥1% among EGFR-mutant and EGFR-wildtype was 55.8% (149/267) and 60.1% (113/188) respectively (p = 0.361). PDL1 ≥50% was significantly associated with higher stage at diagnosis among EGFR-mutant (p < 0.001) but not EGFR-wildtype (p = 0.319). At median follow up of 47 months, 178 patients had relapsed. Among EGFR-mutant, 2-year DFS comparing PD-L1 0% and PD-L1 ≥1% was 79.0% and 68.9% (p = 0.006) while 5-year OS was 87.6% and 70.6% (p = 0.006) respectively. 2-year DFS and 5-year OS by PD-L1 tertile (as shown in table) revealed that higher PD-L1 score was prognostically worse for both DFS and OS among EGFR-mutant. A similar trend was observed among EGFR-wildtype but did not reach statistical significance, apart from PD-L1 ≥50% which had significantly inferior DFS. Conclusions: Higher PD-L1 score was significantly associated with worse DFS and OS among early-stage EGFR-mutated NSCLC, possibly due to higher stage at diagnosis among PDL1 ≥50%. Our study highlights the poor prognosis of PDL1 ≥50% EGFR-mutated NSCLC in a pre-osimertinib era and underscores the importance of personalised risk-stratified adjuvant strategies. [Table: see text]
Neoadjuvant nivolumab in early-stage non–small cell lung cancer (NSCLC): Five-year outcomes.
Authors: Rosner Samuel , Reuss Joshua E. , Zahurak Marianna , Taube Janis M. , Broderick Stephen , Jones David Randolph , Chaft Jamie E. , Forde Patrick M.
Published: June 2022

8537

Background: Neoadjuvant (neoadj) immune checkpoint blockade (ICB) with anti-PD-1 therapy has shown increasing promise for early stage NSCLC, with long-term clinical outcomes still maturing. Our group reported the first phase I/II trial of neoadj nivolumab (nivo) in resectable NSCLC, finding therapy to be safe and feasible. We now present final clinical results from this cohort, representing the longest follow up data for neoadj anti-PD-1 to date. Methods: Two doses of neoadj nivo (3 mg/kg) were given prior to resection in 21 patients (pts) with resectable NSCLC. 5-year (yr) follow-up data, including recurrence-free survival (RFS), overall survival (OS) and association with pathologic response were tabulated. Event time distributions were estimated with the Kaplan-Meier method. All p-values are two-sided with 0.05 significance level. Results: At a median follow up of 63 months, 3-, 4- and 5-yr survival rates were 85, 80, and 80% respectively. RFS rates at 3-, 4- and 5-yrs were 65, 60, and 60% respectively. As previously reported, major pathologic response (MPR: ≤10% viable tumor) was 45%, and pathologic complete response (pCR) rate was 10%. The hazard ratio (HR) for pathologic down-staging was in the direction of improved RFS, without meeting statistical significance (HR 0.36, 95% CI 0.07-1.75, p = 0.2). RFS HR estimates for MPR and an alternative pathologic cut-off of less than 50% residual tumor (RT), were 0.61, (95% CI 0.15-2.44, p = 0.48) and 0.36, (95% CI 0.09-1.51, p = 0.16) respectively. The direction of the effect of pre-treatment PD-L1 positivity (≥1%) was to improve RFS (HR 0.36, 95% CI 0.07-1.85, p = 0.22). At 5-yr follow up, 8 of 9 (89%) pts with MPR were alive and no cancer deaths have occurred. Amongst pts with MPR, 1/9 pts had a cancer recurrence in the mediastinum treated successfully with definitive chemoradiotherapy. Both pts with pCR are alive and without recurrence. Patterns of all recurrences in this cohort are summarized in table 1. No long-term immune-related adverse events have occurred other than one G3 dermatologic event. Conclusions: The 5-yr clinical outcomes for neoadj nivo in resectable NSCLC compare favorably to historical trends. MPR trended toward improved RFS, while definitive conclusions are limited by our cohort size and overall low recurrence rate. Thresholds of %RT beyond pCR and MPR in this setting should be explored in larger prospective studies. PD-L1 expression may play a role in predicting long-term response, but larger prospective studies are needed. Clinical trial information: NCT02259621. [Table: see text]
Racial disparities in receipt of curative surgery for early-stage non–small cell lung cancer in Florida.
Authors: Liu Qinran , Jacobs Kamaria T. , Lopes Gilberto , Brown Clyde P. , Pinheiro Paulo S.
Published: June 2022

8539

Background: Lung cancer is the leading cause of cancer death in the United States. Receipt of curative-intent surgery for early-stage non–small cell lung cancer (NSCLC) is associated with disparities in race and socioeconomic status, which is subsequently related to the outcome of NSCLC. This study aimed to examine the racial disparity in receipt of curative-intent surgery among early-stage NSCLC in Florida. Methods: A total of 80,458 patients with early-stage NSCLC diagnosed from 2005 to 2017 were identified from the statewide cancer registry, Florida Cancer Data System (FCDS). Percentage of patients receiving curative-intent surgery was calculated for each race/ethnicity. FCDS data was linked to discharge data containing comorbidity information for each lung cancer patient. There was a 94% match between FCDS and discharge data. Multivariable logistic regression was used to determine the impact of race on receipt of curative-intent surgery for early-stage NSCLC. Results: Among 80,458 patients with early-stage NSCLC, 66,761 (83.0%) were White, 5,503 (6.8%) were Black and 6,981 (8.7%) were Hispanic. Of note, 69.5% Hispanic patients lived in South Florida. Asian patients (59.9%) had the highest proportion of curative surgery, followed by Hispanics (57.8%), Whites (52.9%) and Blacks (42.6%). In the multivariable model, patients with Charlson Comorbidity Index (CCI)≥3 had 34% lower odds of having curative surgery (OR, 0.66; 95% CI, 0.62 to 0.7) compared to patients who did not have any comorbidity (CCI=0). Highest poverty levels had 27% lower odds of receiving curative-intent surgery compared to lowest (OR: 0.73; 95% CI: 0.68 to 0.78). After adjusting for sociodemographic factors (i.e., age, sex, race, insurance, region) and clinical factors (i.e., histology, AJCC stage, CCI, smoking status), Blacks had 27% lower odds of receiving curative-intent surgery (OR, 0.73; 95% CI, 0.68 to 0.79), whereas Hispanics had 22% (OR, 1.22; 95% CI, 1.14 to 1.30) and Asians had 19% (OR, 1.19; 95% CI, 0.98 to 1.46) higher odds than Whites. In the stratified analysis by regions, Blacks had lower odds of receiving curative-intent surgery than Whites in all regions across Florida while Hispanics had higher odds of receiving surgery than Whites only in South Florida (OR, 1.29; 95% CI, 1.18 to 1.41). Conclusions: There are persistent racial disparities in receipt of curative-intent surgery for early-stage NSCLC in Florida. Specifically, Blacks are receiving less curative-intent surgery, despite adjustments for comorbidities, socio-economic status, and insurance. Ethno-regional differences within different regions of Florida are evident with Hispanics surpassing all other races in receipt of curative treatment in heavily Hispanic South Florida.
Dynamic monitoring circulating tumor DNA in plasma samples by PEAC technology for patients with early-stage non–small cell lung cancer after surgery.
Authors: Li Ning , Wang Bao-Xiao , Ou Wei , Wang Tao , Pu Yue , Zhu Teng-Fei , Hu Xin-Xin , Wang Siyu
Published: June 2022

8547

Background: Local recurrence or distant metastasis after surgery is not rare for early-stage Non-Small Cell Lung Cancer (NSCLC) patients. Present clinicopathological parameters, such as TNM stages and pathological subtype, are limited effective, as Positive Predictive Value (PPV) is low while Negative Predictive Value (NPV) is high. In recent years, circulating tumor DNA (ctDNA) has emerged as a noninvasive method for early diagnosis, prognostic stratification, disease surveillance, and treatment response evaluation. We assessed whether circulating tumor DNA (ctDNA) detected by PEAC technology could be a biomarker for minimal residual disease (MRD) and prediction of postoperative relapse in early-stage NSCLC. Methods: We enrolled 132 NSCLC patients with EGFR, KRAS, NRAS, BRAF and PIK3CA mutations, and obtained plasma samples at five perioperative time points (before surgery, 3-7 days, 6-months, 12-months and 18-months after surgery). Using PEAC technology, somatic mutations in plasma samples were identified and utilized for ctDNA-based MRD analysis. Clinical follow-ups were collected. Results: Our data showed that 32.0% (8 of 25) of patients with positive preoperative ctDNA experienced postoperative relapse, compared with 7.2% (6 of 83) in ctDNA negative patients, demonstrating that preoperative ctDNA status is an effective prognosis factor for NSCLC. In time point of 3-7 days after surgery, plasma samples were obtained from 47 patients, of which 33.3% (2 of 6) with positive ctDNA experienced postoperative relapse, while only 4.9% (2 of 41) in ctDNA negative patients. The result suggests that ctDNA positive in plasma samples of 3-7 days after surgery might be a strong biomarker for MRD detection and relapse prediction. For ctDNA surveillance, plasma samples from 6-months, 12-months and 18-months after surgery were collected and detected. At any one of the three tests ctDNA is positive, 20.0% (8 of 40) patients experienced clinical relapse, while 5.1% (3 of 59) patients with ctDNA negative status at all times relapse. A total of 14 recurrence events had occurred, ctDNA positivity precedes radiological recurrence by a median of 150.5 days (90.5 – 182, P = 0.006). Conclusions: Perioperative ctDNA analysis using PEAC technology is effective in early detection of MRD and relapse prediction, and hence could benefit NSCLC patient management in clinical settings. Clinical trial information: NCT03465241.