bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost-effectiveness analysis of p53 immunohistochemical testing in stage I and II high-risk endometrial cancer.
Authors: Orellana Taylor , Berger Jessica L. , Boisen Michelle M. , Buckanovich Ronald J. , Coffman Lan Gardner , Courtney-Brooks Madeleine , Edwards Robert P. , Mahdi Haider , Olawaiye Alexander , Sukumvanich Paniti , Vargo John , Bhargava Rohit , Beriwal Sushil , Taylor Sarah E. , Smith Kenneth , Lesnock Jamie Lee
Published: June 2021

e18838

Background: PORTEC-3, a phase III clinical trial comparing adjuvant radiation alone (RT) to combined chemoradiation therapy (CTRT) in patients with high-risk endometrial cancer (EC), demonstrated no benefit with CTRT compared to RT for patients with stage I and II EC. However, a subsequent tumor molecular analysis revealed that individuals with stage I and II high-risk EC with p53 mutations had statistically significantly improved progression-free survival (PFS) and clinically significantly improved overall survival (OS) with combined CTRT. As p53 immunohistochemical (IHC) testing and CTRT adds to cost and toxicity, we sought to evaluate the cost-effectiveness of p53 IHC tumor testing in patients with stage I and II high-risk EC. Methods: A Markov decision model was developed to compare two testing strategies in patients with stage I and II high-risk EC: p53 IHC testing vs. no IHC testing. IHC staining for p53 is an accurate and validated surrogate for TP53 mutational status. As a result, p53 IHC testing alone was used in the decision analysis. Data from PORTEC-3 and the subsequent molecular analysis were used for the base case model parameters, including treatment regimen, PFS, OS, and incidence of p53-mutated tumors. Cost and utility data were derived from the Federal Supply Schedule, the Centers for Medicare and Medicaid Services (CMS) Fee Schedules, the Tufts CEA registry, peer-reviewed literature, and expert input. Data analysis was performed using TreeAge Pro Software, 2021. Effectiveness outcomes included quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). Sensitivity analyses were performed in order to identify the influence of individual variables on the overall model. Results: When compared to no testing, p53 IHC testing resulted in a cost savings of $471 per patient while providing an additional 0.310 QALYs. Therefore, p53 IHC testing was less expensive and more effective than no IHC testing and was a dominant strategy in this model. In one-way sensitivity analyses, CTRT and RT costs, discount rate, and percentage of p53 mutations detected had the most impact on the model; however, p53 IHC testing remained a cost-saving strategy over all parameter ranges examined. Conclusions: For patients with high-risk stage I and II EC, this analysis suggests that p53 IHC testing is cost-effective compared to no testing in determining the costs and benefits of adjuvant chemotherapy. Although additional studies are warranted, this data provides further support for the role of molecular-based treatment decisions for high-risk stage I and II endometrial cancer.
Interventions to alleviate financial toxicity among patients with cancer: A systematic review.
Authors: Arastu Asad , Hamilton Andrew , Chen Emerson Yu-sheng
Published: June 2021

e18841

Background: Financial toxicity (FT) has become a recognized side effect associated with cancer diagnosis and treatment; however, there is little data on what interventions have proven to be effective at mitigating the financial burden patients might face. Methods: A systematic review following the Preferred Reporting Items for Systematic Reviews and Met-Analysis (PRISMA) guidelines was conducted in MEDLINE, Embase, and PsycInfo. Broad terminology to capture FT and all possible interventions was used to identify articles published through June 25, 2020 in MEDLINE and July 31, 2020 in Embase and PsycInfo. We excluded systematic reviews, studies not conducted in the United States, with non-adult participants, or those that did not examine an intervention to directly alleviate FT. Two independent reviewers (AA and EYC) reviewed all abstracts to identify which articles met inclusion criteria. An inductive approach was used to thematically categorize unique intervention strategies. Results: A total of 1126 abstracts were identified from the initial search strategy, and 9 met final inclusion criteria. Across these studies, 12 distinct strategies were reported in 27 unique occurrences. They were mapped into four broad domains: 1) patient assistance programs (PAPs) through pharmaceutical company and/or charity sponsored programs, 2) financial navigators who provide counseling and community resources, 3) direct coverage through free medications or payments, and 4) indirect coverage for related services (e.g. transportation). Direct coverage was most commonly proposed, 15/27 (56%) of interventions, followed by PAPs 5/27 (18%), financial navigators 4/27 (15%), and indirect costs 3/27 (11%). These interventions led to outcomes including: cost savings to patients in 5/9 studies (56%), alleviated fears surrounding cost of treatment in 2/9 (22%), earlier medication fills in 1/9 (11%), and decreased anxiety on a self-reported Likert scale in 1/9 (11%). Conclusions: While potential solutions to FT from cancer care remain unclear, this systematic review demonstrates that particular implemented strategies have lessened patient expenses, improved therapy adherence, or helped patients live better. Additional resources could help equip providers and institutions on how to use existing infrastructure (PAPs) or how to deploy additional workforce to diminish FT.
The effect of different types of allogeneic hematopoietic stem cell transplantation donors in Philadelphia chromosome-positive acute lymphoblastic leukemia during tyrosine kinase inhibitors era: A systematic review and meta-analysis.
Authors: Ponvilawan Ben , Kungwankiattichai Smith , Charoenngam Nipith , Owattanapanich Weerapat
Published: June 2021

e19022

Background: Matched donor (MD) allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently the preferred choice of treatment in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who achieve complete remission. However, the unavailability of the appropriate donor remains a problem for a large group of patients. This systematic review and meta-analysis were conducted to investigate the effect of allo-HSCT from different types of the donor in Ph+ ALL patients who received tyrosine kinase inhibitors (TKIs). Methods: Studies from EMBASE and MEDLINE databases were identified from inception to December 2020 using search terms related to “Ph+ ALL” and “HSCT.” Eligible studies must be either randomized controlled trials or cohort studies with Ph+ ALL patients who received a TKI and allo-HSCT. The primary outcome of interest, consisting of overall survival (OS) or relapse-free survival (RFS), must be reported as the number of patients in each donor type. The Hantel-Maenszel method was implemented for combining effect estimates and associated 95% confidence interval (CI) from each. Results: Thirteen cohort studies were included for the meta-analysis. Haploidentical (HID)-HSCT for Ph+ ALL patients resulted in superior RFS than MD-HSCT with pooled odds ratio (OR) 1.64 (95%CI, 1.07–2.53; I2=0%) while had comparable OS (pooled OR 1.11 (95%CI, 0.74–1.69; I2=0%). Although HID-HSCT had significantly less relapse rate compared to the other group (pooled OR 0.53; 95%CI, 0.33–0.86; I2=0%), it also carried increased risks of graft-versus-host disease (GVHD) (pooled OR of acute GVHD rate 2.12; 95%CI, 1.05–4.31; I2=0% and chronic GVHD rate 1.63; 95%CI, 1.01–2.62; I2=0%). Matched sibling-HSCT, matched unrelated-HSCT, and cord blood-HSCT had the comparable OS and RFS to HID-HSCT. Conclusions: This systematic review and meta-analysis showed that HID-HSCT is as effective as MD-HSCT, and appears to be safe to implement in Ph+ ALL patients which could become useful in the case where there was no available donor.
Acute polymyositis presenting as chronic graft-versus-host disease: A systemic review.
Authors: Basit Abdul , Shahzad Moazzam , Chaudhary Sibgha Gull , Khalid Fatima , Ahmed Nausheen , Khurana Sharad , Ganguly Siddhartha , Abhyankar Sunil H. , McGuirk Joseph , Mushtaq Muhammad Umair
Published: June 2021

e19025

Background: Chronic graft-versus-host disease (cGvHD) remains a significant complication of allogenic hematopoietic stem cell transplantation (allo-HSCT), with an estimated incidence of over 50%. Commonly targeted organs are skin, eyes, mouth, gastrointestinal tract, and liver. Muscular involvement and presentation as acute polymyositis (APM) remains a rare manifestation of cGvHD. We present a systemic review of APM associated with cGvHD to summarize current evidence regarding epidemiology, clinical presentation, diagnosis, treatment, and prognosis. Methods: A systemic review was conducting following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We screened 97 articles from 3 databases (PubMed, Embase, and Cochrane) using the MeSH terms and keywords for “Allogenic stem cell transplantation,” “Chronic graft-versus-host disease,” “Polymyositis” and “Myositis” from the date of inception to Jan 2021. After excluding duplicate, review and non-relevant articles, we included 36 studies (3 retrospective, others case series/reports) reporting APM associated with cGvHD after allo-HSCT. Results: We identified 72 patients, presented with APM associated with cGvHD after allo-HSCT. It involves cases of all ages, with male predominance. The onset of APM ranges as early as 100 days to 5 years, with a median range of 1.6 years post-allo-HSCT. Over half (59%) of patients had prior acute GvHD. Majority (85%) of cases presented with myalgia and progressive bilateral proximal muscle weakness with elevated Creatine phosphokinase (CPK) and/or Aldolase. Isolated presentation of APM without other manifestations of GvHD was rare, and concurrent skin involvement was present in 42% cases. Steroids remain the mainstay of treatment, achieving complete treatment response in up to 78% of cases. In some refractory cases, Rituximab has also been effective. Conclusions: APM can present as a sole manifestation of cGvHD with an estimated incidence of up to 3.4%. Diagnosis can be challenging as it can mimic idiopathic polymyositis. Radiologically targeted muscle biopsy showing characteristic myonecrosis remains the gold standard for diagnosis. Most (90%) cases respond to steroids and immunosuppression agents. Nevertheless, refractory cases remain challenging to treat and can cause significant morbidity and mortality. Characteristics of APM in 3 cohorts of allo-HSCT patients.[Table: see text]
Association of post-transplant outcomes with induction intensity in patients with acute myeloid leukemia.
Authors: Rebechi Melanie , Sahasrabudhe Kieran , Huang Ying , Elder Patrick , Blaser Bradley Wayne , Brammer Jonathan Edward , Choe Hannah Kyung , Efebera Yvonne Adeduni , Eisfeld Ann-Kathrin , Jaglowski Samantha , Larkin Karilyn T.M. , Long Meixiao , Mims Alice S. , Penza Sam L. , Saad Ayman A. , Vasu Sumithira , Wall Sarah Allison
Published: June 2021

e19026

Background: The USFDA has recently approved several oral targeted therapies for the treatment of acute myeloid leukemia (AML). The relative survival impact of these agents vs standard induction chemotherapy in the frontline setting is unknown, especially in patients who undergo allogeneic hematopoietic cell transplant (HCT). Methods: This is a retrospective, single-institution study of 125 patients with AML diagnosed 2015-2020 who received HCT. Patients were included if induced with high intensity chemotherapy (HiC) or lower intensity targeted therapy (LITT). HiC was defined as cytarabine + anthracycline given on a “7+3” based schedule. LITT was defined as venetoclax, gilteritinib, enasidenib, or ivosidenib alone or combined with hypomethylating agent. Patients receiving liposomal cytarabine-daunorubicin were excluded. Outcomes of interest were overall survival (OS), non-relapse mortality (NRM), and cumulative incidence of relapse (CIR). Between-groups analysis was conducted comparing receipt of any HiC to LITT only. OS was analyzed by Kaplan-Meier method and compared using log-rank test; NRM and CIR was estimated through cumulative incidence function and compared by Fine-Gray test. Results: Of 125 HCT recipients, 108 received any HiC and 17 LITT only. Two patients received HiC after suboptimal response to LITT. Median age at HCT was 61 years, 48% were female, and 90% were in complete remission at HCT. Population characteristics and outcomes as well as between-groups comparison are presented in the table. LITT only group was older with longer time to HCT and exclusively received RIC. With median follow-up of 23 months, median OS had not been reached. There were no statistically significant differences in median OS or one-year NRM or CIR between groups. Conclusions: Despite differences in age, conditioning regimen, and time to HCT in patients receiving any HiC vs LITT only, we have shown similar OS, CIR, and NRM. Difference in age is in contrast to lack of difference in HCT-CI and KPS, but is partially explained by limited access to LITT for younger patients. Longer time to HCT among LITT only recipients represents a major opportunity for pre-HCT optimization of recipient health. Prospective study from time of diagnosis will be important to understanding the appropriate use of LITT in HCT-eligible patients.[Table: see text]
Updated overall survival of eltanexor for the treatment of patients with hypomethylating agent refractory myelodysplastic syndrome.
Authors: Lee Sangmin , Mohan Sanjay , Knupp Jessica , Chamoun Kamal , BAI Xiang , Ma Xiwen , Shah Jatin J. , Kauffman Michael , Shacham Sharon , Bhatnagar Bhavana
Published: June 2021

e19037

Background: Patients (pts) with myelodysplastic syndrome (MDS) refractory to hypomethylating agents (HMAs) have limited therapeutic options and a dismal prognosis with a median overall survival (mOS) of 4-6 months. Eltanexor (ELTA) is a second-generation, oral, selective inhibitor of nuclear export (SINE) compound that showed anti-tumor activity and lower brain penetration compared to selinexor (SEL) in nonclinical models. It was hypothesized that ELTA could be dosed more frequently than SEL with a lower incidence of centrally mediated nausea. Early results from a phase 1/2 study of ELTA in pts with HMA refractory MDS showed anti-tumor activity with marrow complete response (mCR) and stable disease (SD); side effects were primarily low-grade, dose-dependent, and reversible (Lee et al. ASH 2019). In this abstract, we provide a subgroup analysis of the efficacy evaluable population with an update on mOS in the same population. Methods: This phase 1/2 study (NCT02649790) evaluated single-agent ELTA in pts with higher-risk MDS, ie, high-risk or intermediate-2 MDS by International Prognostic Scoring System (IPSS) and 5%-19% myeloblasts. Out of 20 pts enrolled, 15 pts were evaluable for efficacy and constitute the population studied in this analysis. Two doses of ELTA were evaluated: 10 mg (n=5) or 20 mg (n=15) every day for 5 days per week of a 28-day cycle. Results: As of 1 Feb 2021, the 15 pts evaluable for efficacy (median age 76 years; range 62-89) had a median of 2 prior treatment regimens (range 1-4); 93% had high/int-2 risk per IPSS. Of the 20 enrolled patients, 7 (35%) had mCR, and 5 (25%) had SD for a total disease control (mCR+SD) rate of 60%. Of the 15 pts evaluable for efficacy, 7 (47%) had mCR and 5 (33%) had SD. In the 10-mg cohort (n=5), all pts derived clinical benefit with 3 pts (60%) reaching mCR and 2 pts (40%) SD. In the 20-mg cohort (n=10), 4 pts (40%) had mCR and 3 (30%) had SD. Four pts had hematologic improvement (HI) and became transfusion independent for at least 8 weeks including 2 pts with tri-lineage HI. OS for pts who reached mCR (n=7) was significantly longer than for pts who did not reach mCR (n=8): median 11.86 vs 8.67 months (mo) (hazard ratio [HR]=0.27, p=0.05), and significantly longer than OS for pts with PD (n=3, mOS=3.15 mo, HR=0.23, p=0.04). Pts with disease control (n=12) had numerically longer mOS than pts with PD (9.86 vs 3.15 mo, HR=0.38, p=0.09). Pts with HI had a mOS of 10.58 months. Conclusions: Single-agent oral ELTA was active in pts with high-risk, HMA refractory MDS. Pts with mCR had significantly longer mOS than pts without mCR or with PD. Further evaluation of ELTA in MDS as a single agent and in combination with other agents is ongoing. Clinical trial information: NCT02649790.
Rate of seroconversion for routine vaccinations in patients with chronic lymphocytic leukemia on ibrutinib.
Authors: Ammad Ud Din Mohammad , Jamshed Saad
Published: June 2021

e19509

Background: It is unclear whether Bruton tyrosine kinase inhibitors (BTKi) contribute to the humoral dysfunction in chronic lymphocytic leukemia. Methods: A literature search of PubMed, EmCare, and Google Scholar was performed on December 5, 2020. Five studies met inclusion criteria out of 249 studies per PRISMA guidelines (n = 244). Results: Pleyer et al. and Zent et al. showed an adequate recall humoral response to the shingle vaccine (41.5% and 75% seroconversion rate respectively), however, de novo response to hepatitis B vaccine was greatly reduced. Conflicting results were seen for the influenza vaccine as Sun et al. showed a significant increase in post-vaccination geometric mean titers for all three strains while only 7% of patients demonstrated seroconversion in the study by Douglas et al. None of the patients responded to the pneumococcal conjugate vaccine in a study by Andrick et al, though the results were not statistically significant (p = 0.029) (Table). Conclusions: Treatment with BTKi may not cause significant detrimental response to immunization but further studies are needed to elucidate longterm effects especially in patients with prior exposure to anti-CD20 antibodies.[Table: see text]
Treatment outcomes of stage IE intestinal extra-nodal marginal zone lymphoma: A National Cancer Database study.
Authors: Thomes Reggie M , Parsons Benjamin Marshall , Borgert Andrew J. , Frankki Susan M.
Published: June 2021

e19530

Background: Extra-nodal marginal zone lymphoma is a rare, indolent non-Hodgkin lymphoma. Classically it involves the gastric mucosa and is associated with chronic infection, but it can also be found in the lower gastrointestinal (GI) tract. No standard therapy has been established for early stage disease in the small intestine, colon or rectum though multiple strategies have been employed. Little is known regarding the natural history and long-term outcomes of this disease when confined to the lower GI tract. We used the National Cancer Database (NCDB) to evaluate this patient population based upon treatment modality and disease site. Methods: Patients meeting the inclusion criteria were extracted from the 2017 Extra-Nodal Non-Hodgkin’s Lymphoma NCDB. Patients were grouped by primary treatment or observation status. Clinical and demographic factors were compared between the treatment groups via chi-square, Fisher’s exact and the Kruskal-Wallis tests. Comparison of Overall Survival (OS) between groups utilized either univariable log-rank comparison of the Kaplan-Meier estimator or multivariable Cox proportional hazards regression modelling, with patients censored at date of last contact. All analyses were performed with the SAS software suite, version 9.4. Results: 775 patients were identified with stage IE extra-nodal marginal zone lymphoma of the small intestine, colon or rectum with treatment and follow-up data. Prevalence increased over time. Median age at diagnosis was 65, with a ten-year overall survival for the entire cohort of 74.8% (69.8% - 79.0%). Location of disease was small intestine in 286 patients (36.9%), colon in 361 patients (46.6%) and rectum in 128 patients (16.5%). Ten-year overall survival was significantly worse for a small intestine primary site compared to colon and rectum primary sites (64.9% (55.6% - 72.6%) vs 81.5% (74.9% - 86.5%) and 80.9% (68.5% - 88.8%) respectively; p-value 0.013). Initial treatment was surgery in 361 patients (46.6%), radiation in 99 patients (12.8%), chemotherapy and/or immunotherapy in 120 patients (15.5%), and observation in 195 patients (25.1%). No significant differences in 5-year or 10-year survival were seen between treatment groups. Conclusions: Observation is a reasonable management strategy in patients with stage IE lower intestinal tract extra-nodal marginal zone lymphoma; survival is similar to those who received surgery, radiation or systemic therapy. Those with small intestine primary site had worse overall survival, irrespective of treatment modality, when compared to colon and rectum disease sites.
Same-day pegfilgrastim or pegfilgrastim-cbqv prophylaxis in miniCHOP chemotherapy based regimens for non-Hodgkin lymphoma.
Authors: Bartels Trace , McBride Ali , AlRawashdh Neda , Moore Logan , Persky Daniel O , Abraham Ivo
Published: June 2021

e19542

Background: Non-Hodgkin’s lymphoma, specifically, diffuse large B-cell lymphoma (DLBCL) is most frequently diagnosed among older patients. The utilization of a reduced dose of cyclophosphamide, doxorubicin, vincristine, and prednisone (miniCHOP) chemotherapy-based regimen has an improved tolerance and toxicity profile in select patient populations. Prophylaxis with pegfilgrastim or its biosimilar pegfilgrastim-cbqv is administration on the same day of chemotherapy in all patients with MiniCHOP at The University of Arizona Cancer Center (UACC). We report here on the first study to address the safety and efficacy of same day pegfilgrastim administration in lymphoma patients receiving MiniCHOP. Methods: A retrospective, single center, cohort study was conducted at UACC between October 1, 2013 and October 2020 to evaluate lymphoma patients who were treated with miniR-CHOP and given pegfilgrastim or its biosimilar (pegfilgrastim-cbqv) for FN prophylaxis. The primary objective was to compare the incidence of FN across all cycles of chemotherapy and after the first cycle of chemotherapy in DLBCL patients on miniR-CHOP and provided with next-day versus same-day pegfilgrastim administration. Our secondary outcomes of interests were incidence of chemotherapy-induced neutropenia (CIN) grade 3/4; hospitalization; anti-biotics administration; and chemotherapy dose-reduction or delays. Results: A total of 100 cycles of miniR-CHOP were received, of these pegfilgrastim was administered on same-day of chemotherapy in 95 cycles and five cycles on the next-day of chemotherapy. Among all cycles the incidence of FN was 5.3% vs. 0.0 ( P= 1.00); CIN 3/4 was 10.5% vs. 0.0 ( P= 1.00); hospitalization was 10.5% vs. 20.0% ( P= 0.45), anti-biotics administration was 6.3% vs. 40.0% ( P= 0.05) and the chemotherapy dose delays or reductions was 16.8% vs. 0.0% ( P= 0.99). In the first cycle of chemotherapy, the incidence of FN was 14.3% vs. 0.0% ( P= 1.00), CIN 3/4 was 21.4% vs. 0.0 ( P= 1.00), hospitalization 28.6% vs. 25.0% ( P= 0.99), and the anti-biotics administration was 21.4% vs. 50.0% ( P= 0.53) for same-day vs. next-day study groups. Conclusions: In our analysis, we have shown that same-day pegfilgrastim or pegfilgrastim-cbqv was safe and effective in lymphoma patients receiving miniR-CHOP. There was no significant increase in FN or delayed engraftment in either group. Future prospective studies are warranted to address the safety and efficacy profile of same day pegfilgrastim or a pegfilgrastim biosimilars in elderly lymphoma patients.
Association of PET/CT response assessment prior to CAR T-cell infusion with outcomes after CAR T-cell therapy in aggressive B-cell lymphomas.
Authors: Nader Alexandra , Lee Hwan , Sellmyer Mark , Landsburg Daniel Jeffrey , Nasta Sunita , Gerson James , Svoboda Jakub , Barta Stefan K. , Weber Elizabeth , Schuster Stephen J. , Chong Elise A.
Published: June 2021

e19568

Background: Anti-CD19 chimeric antigen receptor modified T-cell therapies (CAR-T) have expanded the treatment possibilities for many patients with relapsed/refractory (R/R) aggressive large B-cell lymphomas (B-NHL) but fails to achieve remissions in a considerable proportion of patients. In this study, we examined whether response to systemic therapy prior to CAR T-cell infusion is associated with outcome. Methods: We analyzed a retrospective dataset of R/R B-NHL patients (pts) treated with commercially available CAR-T at the University of Pennsylvania treated from April 2018 to August 2020. 18F-FDG PET/CT scans obtained directly prior to and after CAR-T therapy were re-evaluated for response by an independent radiologist using the Lugano 2014 criteria. Association between pre-therapy and post-therapy responses were examined using Fisher’s exact test. Results: 50 pts with aggressive R/R B-NHL were enrolled. 34 pts received tisagenlecleucel and 16 received axi-cel. Median age was 61 (range 29-82), and 27 pts (54%) were men. Most pts (n = 48, 96%) had ECOG performance status of 0-1, with a median number of 3 prior therapies (range 1-11). 14 (28%) of pts had LDH elevation at time of CAR T cell infusion. Median time from pre-therapy PET/CT to infusion was 47 days (range: 6-155). Median PFS was 3.4 months. Prior to CAR T cell infusion, responses were as follows: 12 complete response (CR), 9 partial response (PR), 8 stable disease (SD) and 21 progressive disease (PD). Post-therapy responses were: 20 CR, 5 PR, 2 SD, and 23 PD. 67% of pts with a CR pre-therapy had continued CR after CAR T-cell infusion, whereas 32% pf pts without a CR had a CR after infusion (p < 0.05). There was a trend toward CR/PR immediately prior to CAR T cell infusion being significantly associated with CR after CAR-T. We found that high metabolic tumor volume ( > 350cc vs ≤350cc) was associated with poorer PFS (log rank, p = 0.05). We did not find elevated LDH or use of bridging therapy to be associated with response to CAR-T. Conclusions: This is the largest report of lymphoma patients treated with CAR-T while in remission to date and suggests the importance of optimizing clinical response prior to CAR-T. Although patients in CR were excluded from the registrational trials, it is notable that patients in CR prior to CAR-T had a high rate of CR post CAR T cells despite the absence of active lymphoma on imaging. Longer follow-up is needed to confirm these early observations.
Isatuximab plus carfilzomib and dexamethasone in east Asian patients with relapsed multiple myeloma: IKEMA subgroup analysis.
Authors: Kim Kihyun , Min Chang Ki , Koh Youngil , Ishizawa Kenichi , Kim Sung-Hyun , Ito Shigeki , Junji Tanaka , Uchiyama Michihiro , Kawano Yawara , Kim Jin Seok , Moreau Philippe , Martin Thomas G. , Dong Yvonne , Risse Marie-Laure , Suzuki Kenshi
Published: June 2021

e20015

Background: The Phase 3 IKEMA study (NCT03275285) demonstrated that isatuximab (Isa) plus carfilzomib and dexamethasone (Kd) significantly improved progression-free survival (PFS) compared with Kd in patients (pts) with relapsed multiple myeloma (RMM) (hazard ratio [HR] 0.53; 99% confidence interval [CI] 0.32–0.89; P= 0.0007). We evaluated the efficacy and safety of Isa-Kd in the East Asian patients (19 Japanese, 27 Korean). Methods: RMM pts who received 1-3 prior lines of therapy were stratified to receive Isa-Kd or Kd. Isa-Kd arm received Isa (10 mg/kg intravenously) weekly for 4 weeks, then every 2 weeks. Both arms received K (20 mg/m2 days 1-2, 56 mg/m2 thereafter) twice-weekly for 3 of 4 weeks, and d (20 mg) twice-weekly. Treatment continued until disease progression or unacceptable adverse events (AE). The primary endpoint was prolongation of PFS. Key secondary endpoints included; very good partial response or better (≥VGPR), complete response (CR) rate and minimal residual disease negativity (MRD–) rate. Results: East Asian pts (25 Isa-Kd, 21 Kd) were randomized. Pt characteristics were similar in the East Asian subgroup compared with the intent to treat (ITT) population (N = 302). Median age (Isa-Kd 64.0 [range 45–83] years vs Kd 60.0 [range 33–73] years); median prior lines Isa-Kd 2.0 (range 1–3) vs Kd 1.0 (range 1–3); refractory to lenalidomide 16.0% Isa-Kd vs 47.6% Kd; refractory to PI 20.0% Isa-Kd vs 33.3% Kd; high-risk cytogenetics 48.0% Isa-Kd vs 42.9% Kd. After a median follow-up of 20.7 months, the addition of Isa to Kd improved ≥VGPR, CR and MRD– rates (Table). The HR 0.64 (95%CI: 0.231-1.764) for disease progression or death favored Isa-Kd. Grade ≥3 AEs were observed in 79.2% Isa-Kd vs 55.0% Kd pts, serious TEAEs in 45.8% Isa-Kd vs 50.0% Kd; TEAEs leading to treatment discontinuation were lower in the Isa-Kd group (4.2% Isa-Kd vs 10.0% Kd). Overall, 64.0% Isa-Kd vs 42.9% Kd pts were still receiving treatment. Conclusions: Efficacy and safety results of Isa-Kd in East Asian pts are consistent with the results of the overall IKEMA population, in which significantly better efficacy (PFS, CR, ≥VGPR and MRD– rate) was reported in favor of Isa-Kd without an increase in the number of patients with serious TEAEs or discontinuations. Isa-Kd is a potential treatment option for East Asian pts with RMM. Clinical trial information: NCT03275285. [Table: see text]
Distinct clinical characteristics and prognosis of ground-glass opacity-type lung cancer: A systematic review and meta-analysis.
Authors: Chongxi Ren , Ruisheng Yin , Hongqiao Wang , Hongchen Wang , Tong Zhou , Fengying Li , Xin Wang , Meng Li , Hongxia Qi , Sheng Li , Haixia Ren , Xuefeng Li , Fengyan Li , Juan Wang , Fengshuo Yang
Published: June 2021

e20505

Background: Lung ground-glass opacity (GGO), a hazy increased opacity on computed tomography with preservation of bronchial and vascular margins, has been shown to be associated with early-stage lung cancer. With the increasing prevalence of ground-glass opacity-type lung cancer (GGO-LC), more researches have focused on the diagnosis and treatment of this early stage lung cancer; however, the clinical characteristics and survival outcomes of this disease has not yet been fully elucidated. Aim: To analyze and review the clinicopathological characteristics for GGO-LC and to identify the optimal treatment strategies in this select population. A systematic review and meta-analysis of the literature were carried out. The study was registered (CRD42021228774). Methods: We did a systematic review and meta-analysis of observational studies published from database inception to June 30, 2020, which reported on clinicopathological characteristics, management and survival outcomes in patients with GGO-LC. Studies were identified by searches in PubMed, MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and by hand searching of previous publications. We extracted the general information to perform the meta-analysis, mainly focusing on age, gender, and smoking status. We also extracted treatment and prognosis information to assess the effect of treatment strategies on overall survival (OS). Robustness of pooled estimates from random-effects models was considered with sensitivity analyses, meta-regression, and subgroup analyses. All statistical analyses were performed with Stata 16.0. Results: Data on 9444 patients in 27 observational studies were included. GGO-type lung cancer was typically characterized as non-invasively or minimally invasively low-grade adenocarcinomas. Therapeutic intervention for these early stage lung cancers was an important opportunity for decreasing overall mortality of lung cancer. The final pooled analysis showed that the average age at diagnosis, female proportion and non-smoking proportion of patients with GGO-LC was 57.7 (95% CI, 53.9-61.5, P < 0.001, I2 = 92.9%), 0.591 (95% CI, 0.563-0.619, P < 0.001, I2 = 86.7%), and 0.631 (95% CI, 0.556-0.706, P < 0.001, I2 = 98.3%), respectively. The pooled overall survival rate was 96.2% (95% CI, 0.954 to 0.970, P < 0.001, I2 = 78.9%). The results showed that the majority of GGO-LC patients had good survival outcomes, presenting a significant proportion of young, female and non-or light smokers. Conclusions: From our analysis, it demonstrates that the patients with GGO-LC may be relatively young females and non-or light smoking history, and had better prognosis. However, there are some limitations in the present study, and more evidence is necessary to wait for more results from RCT to draw a valid conclusion.
Does multiplicity of synchronous multiple lung primaries (SMLPs) affect prognosis.
Authors: Xue RuoBing , Maharaj Satish , Kumar Rohit , Kloecker Goetz H.
Published: June 2021

e20530

Background: SMLPs are detected more commonly due to advancements in screening technology. Their workup and classification; however, are still lacking a clear standard. T stage of the largest lesion has been used as the major prognostic marker. This; however, does not take the number of SMLPs and their genomic drivers into consideration. This study aims to identify and review common risk factors associated with SMLPs and determine whether the number of primaries influence the prognosis. Methods: A systematic review of the literature published between 2000 and 2021 was conducted through PubMed and Medline by using the combination of keywords, including: “synchronous multiple primary lung cancer”, “simultaneous multifocal lung cancer”, “synchronous solitary lung metastasis”, “risk factor” and “prognosis”. A total of fifty studies were identified, among them only sixteen retrospective research articles and two review articles were relevant to the study at hand. Results: Sixteen retrospective studies including a total of 1685 eligible patients were reviewed. Thirteen of these studies reported the main histology type to be adenocarcinoma with a ratio ranging from 35% to 96.8%. Eight studies have reported the numbers of synchronous primary lung cancers, including one study found 11 SMLPs. Among these, one study by van Rens found number of SMLPs impact prognosis adversely compared to a single lung cancer. However, three other studies demonstrated multiple SMPLs do not adversely affect survival (Finley et al, 2010; Kocaturk et al, 2011; Li et al, 2020). Four of the sixteen studies analysed the effect of multiple lobes involvement and distance between tumors, with varying conclusions; two studies reported no difference in prognosis while one study revealed worse survival with multiple lobe involvement and one study found favorable outcome. Most studies confirm the usual prognostic factors for SMLPs, including: gender, smoking, type of surgery, comorbidities and adjuvant therapy. The median 5 year OS reported for SMLPs is 66%, with a wide range from 19% to 95.8%.The 3 year OS is 75% in most studies. Conclusions: The data on how the number of SMLPs affects the prognosis is uncertain. The current recommendation to base the decision for adjuvant therapy on the highest T stage is not supported by prospective evidence or consistent among published case series. Considering the recent approval of targeted therapies in early stage lung cancers, a better prognostic scoring system for SMLPs is required.
Concurrent chemoradiotherapy with weekly cisplatin in stage III unresectable non-small cell lung cancer (NSCLC): A local experience with LATAM patients.
Authors: Salinas Carlos , Pinto Negrete Felipe Eduardo , Saavedra Maria Paz , Orlandi Francisco J
Published: June 2021

e20535

Background: Lung cancer is the leading cause of cancer related death worldwide and so is expected in Chile in 2021 accoding to Globocan, with a 12.4% mortality rate last year. Among NSCLC, 35 to 40% present as locally advanced disease, most of them non surgical candidates. Current standard of treatment is platinum-based doublet with concurrent Radiotherapy plus adyuvant durvalumab since 2018. Still many controversies related to different approaches are not settled. Few literature is available concerning a less aggressive approach in order to achieve a more tolerable treatment for the patient preserving effectiveness. Many patients compromise the treatment compliance due to early toxicities. We present our preliminary results of local data consisting in weekly cisplatin plus concurrent standard dose of radiotherapy. Methods: We performed a retrospective review of local database for stage III unresectable NSCLC between 2013 to 2019. Baseline clinical data , treatment modality, toxicities and response rates were recorded for all patients. Outcomes were analyzed by measuring overall response rate (ORR) , progression free (PFS) and overall survival (OS). Toxicities were assessed by CTCAE v5.0 and treatment response by RECIST 1.1 criteria. Results: 54% of the patients were men, 68%ECOG 0 and 32% ECOG 1. Mean BMI of 26 kg / m2. 100% smokers with average 39 packages per year and 71% had some other comorbidity;. 26% had emphysema. Histologic confirmation of 74%adenocarcinom and as. 26% squamous cell carcinoma. Staging analysis showed 23% stage IIIA, 54% stage IIIB, and 23% stage IIIC. Only 6 patients received adjuvant treatment before being diagnosed with stage III disease. Chemoradiotherapy is carried out as follows: 86% cisplatin (median 54.4 mg/m2) as a single weekly dose combined with standard radiotherapy of 60 Gy /30 Fr in a concurrent modality in ???. 74.2% completed follow up after CRT and the remaining 50% received adyuvant durvalumab. 71% of the patients reported some degree (mild, moderate or severe?) of toxicity related to the treatment; 37.1% grade 2 actinic pneumonitis, 11.4% grade 2 actinic esophagitis and 11.4% grade 1 acute renal failure among the most significant. No CTCAE 5.0 grade 4 and 5 toxicities were reported. 82.8% progressed in 15 months average (mean??); with 17% with current stable disease. The ORR was 48,5%. The mOS was 23 months (95% CI [16,7-29,3]) and the mPFS was 10 months (95% CI [8.25-11.75]. Conclusions: Since PACIFIC trial, stage III unresectable NSCLC have experienced a pivotal change in management. Unfortunately, our Public Health Insurance System does not cover access for all pts. This approach reaches similar results described in earlier trials published in the area and could be an option in certain clinical settings.
Incidence of pneumonitis among limited-stage small cell lung cancer patients exposed to concurrent chemoradiation: A systematic literature review and meta-analysis.
Authors: Zu Ke (Kirsten) , Kuang Yuting , Nevo Arianna , Pietanza Maria Catherine , Liu Mike , Deitz Anne , Uyei Jennifer , Darpan Darpan
Published: June 2021

e20592

Background: Concurrent chemoradiation (cCRT) has been the standard first line treatment for patients with limited-stage small cell lung cancer (LS-SCLC) for decades. Despite continued progress in refining chemotherapy and radiation modalities, the prognosis for LS-SCLC remains unsatisfactory with cCRT alone. Recent clinical trials have sought to further improve survival by combining cCRT and other newly developed therapeutic agents in treating LS-SCLC. Severe (grade 3 or higher) pneumonitis is one of the major toxicities related to cCRT. The objective of this study was to establish a benchmark rate of pneumonitis in LS-SCLC patients receiving first line cCRT. Methods: A systematic literature review and meta-analysis was performed in accordance with Cochrane, PRISMA, and Food and Drug Administration guidelines to summarize and quantify the incidence of grade 3−5 and fatal pneumonitis (including radiation pneumonitis) in patients with LS-SCLC exposed to cCRT alone. MEDLINE, Embase, and the Cochrane Central Register were searched from 2014 to July 16, 2020 to identify relevant randomized controlled trials (RCTs) and non-RCT studies (observational studies or non-randomized trials). The study quality of included RCTs and non-RCT studies was evaluated using the Revised Cochrane Risk of Bias Tool for Randomized Trials (RoB2) and the Newcastle-Ottawa scale, respectively. The incidence of pneumonitis across studies was pooled using a frequentist method with correction for zero events, using the metafor package in R 3.6.1. Results: Thirteen studies (4 RCTs, 9 non-RCTs) were included in the review. Patient populations were comparable across studies and the median follow-up ranged from 20−59 months. All patients received etoposide with either cisplatin or carboplatin, and radiation doses, given once or twice daily, ranging from 40−72 Gy. While all RCTs were open-label studies that could have some deviations from the intended interventions, this did not impact the reported incidence of pneumonitis. All non-RCTs were of high quality. Ten studies were included in the meta-analysis (3 RCTs, 7 non-RCTs; 1,539 patients). The pooled incidence of grade 3−5 pneumonitis was 3.28% [95% confidence interval (CI): 1.52−5.04%] in RCTs from random-effects model, and 6.34% [95% CI: 3.64−9.04%] in non-RCTs from fixed-effects model. The pooled incidence risk of grade 5 (fatal) pneumonitis was 0.29% [95% CI: 0.00−0.62%] in RCTs and 0.88% [95% CI: 0.02−1.74%] in non-RCTs, both from fixed-effects model. Conclusions: In LS-SCLC patients exposed to cCRT, the incidence of grade 3−5 pneumonitis and fatal pneumonitis ranges from 3.28−6.34% and 0.29−0.88%, respectively. These results can be used to understand the safety of other therapeutic agents with regard to pneumonitis when used in combination with cCRT to treat patients with LS-SCLC.
Distinct subset of immune cells assessed by multiplex immunohistochemistry correlates with immune phenotype classified by an artificial intelligence-powered tissue analyzer in advanced non-small cell lung cancer.
Authors: Choi Yoon-La , Park Sehhoon , Pereira Sergio , Park Seonwook , Ma Minuk , Shin Jiwon , Shin Jisoo , Paeng Kyunghyun , Yoo Donggeun , Ock Chan-Young , Lee Se-Hoon
Published: June 2021

e21012

Background: Pathologic classification of immune phenotype is challenging since there is no consensus on how to assess spatial relations of tumor-infiltrating lymphocyte (TIL) on cancer epithelium (CE) and cancer stroma (CS) in whole-slide images (WSI). We previously suggested that the artificial intelligence (AI)-powered tissue analyzer, Lunit SCOPE IO, can classify immune phenotype, and that its predictions are correlated with the clinical outcome of immune checkpoint inhibitor (ICI) in non-small cell lung cancer (NSCLC). In this study, we designed a pathologic validation of immune phenotype using multiplex immunohistochemistry. Methods: Lunit SCOPE IO was developed based on a 2.8 x 109 micrometer2 area of CE or CS, and 5.9 x 106 TILs from 3,166 H&E Whole-Slide Image (WSI) of multiple cancer types, annotated by board-certified pathologists. H&E WSIs were divided into 1 mm2-sized tiles, where we classified immune phenotype (IP) based on TIL density on CE and TIL density on CS. Representative IP was determined based on the overall proportion of tile-level IPs in each WSI. Multiplex immunohistochemistry (mIHC) staining with CD3, CD8, CD20, CD68, FOXP3, CK, and DAPI was performed in NSCLC tumor tissues (n = 99) treated with immune checkpoint inhibitors (ICI) at the Samsung Medical Center. A normalized number of cells expressing each marker was calculated by dividing the total number of marker-positive cells by the number of DAPI-positive cells in each WSI. Results: The proportions of inflamed IP, immune-excluded IP, and immune desert IP in the analysis set were 46.5%, 29.3%, and 24.2%. respectively. Median progression-free survival of ICI was 6.4 m in inflamed IP, 1.9 m in immune-excluded IP, and 1.6 m in immune-desert IP (hazard ratio of inflamed versus others: 0.43, confidence interval 0.27-0.68, P = 0.000188). Multiplex IHC results showed that the normalized CD3-positive cells and CD8-positive cells, which play a role of anti-tumor activity, were highly enriched in inflamed IP compared to those in other IPs (CD3: fold change [FC] 1.57, P = 0.0182; CD8: FC 1.24, P = 0.0697), whereas FOXP3-positive cells, linked to the immunosuppressive activity, were enriched in immune-excluded IP (FC 1.26, P = 0.0656). We also noted that CD68-positive cells were significantly enriched in immune-desert IP (FC 1.76, P = 0.00467). Conclusions: The immune cell subset in WSI is distinct according to the immune phenotype, as CD3- or CD8-positive cells are enriched in inflamed IP rather than immune-excluded IP as classified by AI-powered TIL analysis of H&E image.
Patient-derived lung cancer organoids for the selection of therapeutic options in an ALK-rearranged tumor.
Authors: Jimenez Munarriz Beatriz , Dantes Zahra , De Castro Javier , Navarro Paloma , Yagüe Monica , Barquin Arantzazu , Rodriguez-Moreno Juan Francisco , Sevillano Elena , Ruiz Sergio , del Barrio Anabel , Ledo Gema García , Dorta Miriam , Lorduy Ana Collazo , Calvo Emiliano , García-Donas Jesús , Serrano Sandra , Manjunath Apoorva , Ferreira Luciana , Hefel Barbara , Remon Jordi
Published: June 2021

e21014

Background: ALK rearrangements are key targets in non-small-cell lung cancer (NSCLC). Unfortunately, the optimal sequential strategy of ALK-tyrosine kinase inhibitors (TKI) remains to be defined. Testing drug sensitivity in patient derived organoids (PDOs) could support a rational drug selection in this setting. Methods: We designed an observational study assessing the correlation between drug sensitivity of PDOs established in Invitrocue and the clinical outcome in our institution. To date, forty cases have been included, of which nine were lung cancers. Results: PDO was sucessfully established in 7/9 cases (77%). Three patients did not receive any of the drugs tested in vitro due to clinical deterioration. One patient was deemed as sensitive to carboplatin but tumor showed to be resistant. A meaningful correlation was observed in an oncogenic addicted tumor. A 54-year-old never-smoker man who had been diagnosed with lung adenocarcinoma stage IVa (T3N1M1a). He received standard first-line therapy with platinum-based chemotherapy, immunotherapy and antiangiogenics achieving tumor progression. A next-generation sequencing (NGS) panel revealed the presence of the EML4-ALK fusion variant 3a/b. The patient started alectinib but showed progression after 12 months. A second NGS panel did not identify any new ALK resistance mutation but acquiring TP53. Treatment was switched to brigatinib with no response. Finally, fresh tumor tissue was obtained from a liver biopsy to establish PDOs and drug sensitivity to 8 compounds was tested. The In vitro results demonstrated no activity of lorlatinib but a strong response to crizotinib. The patient started Crizotinib 250mg BID achieving partial response after 8 weeks and treatment duration of 6 months. A third liver biopsy for PDOs and NGS revealed acquired ALK C1156Y and I1171T mutations that confer resistance to crizotinib but sensitive to ceritinib, respectively. Conclusions: We present clinical evidence that PDOs are an alternative tool in oncogenic addicted tumors helping to guide treatment decisions and increasing a more personalized sequential treatment approach.