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Background: Optimal consolidation for young R/R FL in the rituximab age remains uncertain and the benefit of ASCT is not clearly established. Aims: The FIL FLAZ12 trial (NCT01827605) is a prospective, multicenter, randomized, phase 3 trial, comparing RIT versus ASCT, as consolidation after chemoimmunotherapy, both followed by R maintenance in R/R FL. Methods: Pts aged 18-65 yrs, with R/R FL after 1 or 2 lines of chemoimmunotherapy, without significant comorbidities were enrolled. Patients received 3 courses of therapy chosen by the investigator among RCHOP, R-DHAP, R-FM, R-ICE, R-IEV or R-B. Pts achieving at least PR (according to Cheson et al. 2007) were randomized 1:1 to either RIT or ASCT before CD34+ collection. Conditioning for ASCT was BEAM or TEAM. RIT was given as previously described (Morschhauser et al., 2008). After consolidation, pts received R maintenance every 3 months for eight courses. Primary endpoint was PFS. Considering ASCT toxicity, it was hypothesized to be a superior choice, if capable of increasing 3-years PFS from 40% to 60% (two-side log-rank test with alpha of 5% and a power of 85%). Clinical secondary endpoints were ORR, CRR, OS, EFS and TTF. Results: Between Aug 2012, and Sep 2019, 164 pts were screened and 159 enrolled by 38 FIL Centers (enrolled population). Unfortunately, the study was prematurely closed due to low accrual. The data were analyzed on an ITT basis on May 2, 2021 with a median follow-up (mFU) from enrollment of 43 months and 75 PFS events. The two arms were clinically well balanced, with median age of 57 yrs (IQR 49-62), 55% male, 57% stage IV, 20% bulky disease. Tumor re-biopsy was performed in 79% pts. POD-24, retrospectively assessed was observed in 32% of pts. Two pts (1%) did not start treatment (non-confirmed histology and withdrawal). Sixteen (10%) pts discontinued before randomization (7 SD, 3 PD, 3 AE, 1 withdrawal, 2 poor compliance) and 141 (89%) were randomized to either RIT (71) or ASCT (70) (randomized population). Of these 19 (13%) (RIT 8, ASCT 11) did not receive the planned consolidation due to 7 PD, 4 AE, 1 medical decision, 2 poor mobilization, 2 withdrawals, 1 poor compliance, 2 protocol breaches, while 63 (89%) received RIT and 59 (84%) ASCT. After RIT, 61% of pts achieved CR and 23% PR, while after ASCT these were 70% and 9%. Estimated PFS at 3 yrs was 60% (95% CI: 46%-71%) in the RIT arm vs. 59% (95% CI:45%-70%) in the ASCT arm, p = 0.8613 (HR 0.96, 95%CI: 0.57,1.59). (Figure 1) 3yrs-OS was again superimposable in the two arms: 83% (95%CI: 69%-91%) in the RIT vs 85% (95% CI: 72%-91%) in the ASCT, p = 0.8310 (HR 1.10, 95%CI: 0.45,2.72). Grade ≥ 3 hematological toxicity was 46% in the RIT vs 94% in the ASCT arm (p < 0.001). For ASCT vs RIT grade ≥3 neutropenia occurred in 94% vs 41% of pts (p < 0.001). During follow-up, 4 pts died in remission: 1 AML (RIT), 2 SARS-COV2 infections (RIT) and 1 pneumonia (ASCT). Second cancers occurred in 3 pts after RIT and 7 after ASCT (p = 0.480). Multivariable analysis for PFS indicated POD-24, male sex, LDH and refractory disease as adverse parameters. Subgroup analysis for PFS including gender, age, LDH, POD-24 and extranodal disease show no subgroup favoring RIT nor ASCT. Image: Summary/Conclusion: Even if prematurely interrupted, our study demonstrated no meaningful difference in efficacy between ASCT and RIT, but ASCT was more toxic and more demanding for pts and health service. Both strategies induced a similar and favorable long-term outcome suggesting that consolidation programs milder than ASCT require further investigation in R/R FL.
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Ibrutinib is the only once-daily Bruton's tyrosine kinase (BTK) inhibitor with significant survival benefit vs. chemo- and/or immunotherapy in multiple phase 3 studies of patients (pts) with chronic lymphocytic leukemia (CLL). It has profoundly changed the treatment landscape of CLL with the longest follow-up. However, seven years (yrs) after ibrutinib was approved in Italy by regulatory agencies for CLL treatment, available data on the patterns of care of such pts in the setting of clinical practice is limited. Herein we present the first interim analysis (IA) of EVIdeNCE (ClinicalTrials.gov Identifier: NCT03720561), a multicenter, observational clinical study designed to describe the current management of pts receiving ibrutinib in a real-world setting in Italy in terms of retention rate: the study's primary end point. Methods EVIDENCE 312 treatment-naïve (TN) 38% and relapsed/refractory (R/R) 62% pts with CLL according to the iwCLL diagnosis criteria observed at 39 Italian hematological institutions in the period between November 2018 and October 2019. Inclusion criteria were treatment with ibrutinib according to the European Summary of Product Characteristics as per routine clinical practice started within the previous 3 months. The purpose of this IA is to provide demographics and disease characteristics at baseline and a preliminary evaluation of ibrutinib retention rate after one year of follow-up, along with its safety profile. The median age of pts at the time of ibrutinib initiation was 71.0 yrs (range 41.0-89.0), with 60% ≥70 yrs, 63.2% male, and 90% with Eastern Cooperative Oncology Group (ECOG) performance 0-1. Baseline Rai stage 0-I, II, and III-IV accounted for 18.3, 29.7, and 52.1% pts, respectively. Patients in stage IV were observed in 40% of the R/R and 27% in the TN subgroup. Considering 120 pts with known mutational status, del(17p) and/or TP53 mutation were present in 50.0% of pts (TN =52.1%, R/R = 48.6%), while IGHV was unmutated in 35.0% (TN =33.3% and R/R = 36.15) and mutated in 15.0% (TN =14.6%, R/R = 15.3%). At baseline, 62.9% of pts had comorbidities and 30.6% presented with a history of cardiovascular diseases (CVDs). A CIRS score ≥6 was observed in 28.5% of pts. The median time from CLL diagnosis to the start of ibrutinib was 5.1 yrs (TN 1.75 yrs vs. R/R 7.27 yrs). At least 1 treatment-emergent adverse event (TEAE) of any grade was experienced by 70.7% of pts. Frequencies were as follows: infections (30.8%;COVID-19 infections 3.2%), arthralgia (10.8%), neutropenia (9.3%), fatigue (8.4%), diarrhea (7.7%), atrial fibrillation (7.4%;grade 3-4, 4.2%), fever (7.1%), rash (6.4%), anemia (6.1%), and hypertension (4.2%). Mild bleeding TEAEs were reported in 16.1% of pts with no major bleeding event. TEAEs were more frequent in the elderly (≥65 yrs) while no significant differences in the rate of TEAEs were recorded in TN and R/R pts (69.7 vs. 71.4%, respectively). Serious TEAEs were reported in 21.9% of pts. Overall in intention to treat (ITT), 32 deaths (10%) were observed (TN =8, R/R = 24). The most common causes of death were infections (3.5%) and progressive disease (PD) (1.9%). Permanent discontinuation was observed in 56 (18%) of the pts (TN =17.2%, R/R = 18.7%) and it mostly occurred within the first 6 months. The main causes of discontinuation were toxicity (6.1%), PD (3.8%), and death (3.5%). Temporary interruptions (≤3 months without therapy and/or dose modifications) during the whole observation period occurred in 30.3% (TN =35.3%, R/R = 27.2%) and 37.7% (TN =37.5%, R/R = 37.8%) of pts, respectively, mainly determined by toxicity and clinical judgment. Finally, in this first IA after 17.3 months (range 1.1-27.0) median follow-up, the ibrutinib retention rate (calculated as the ratio between the number of patients who retained ibrutinib treatment over the total number of patients at risk) at 1-year was 81.9% [95% confidence interval (CI), 77.2-86.1%] with no difference between TN 83.2% (95% CI, 75.2-89.4%) and R/R 81.2% pts (95% CI, 74.9-86.4%). EVIDENCE is the first realw rld study of ibrutinib use in CLL clinical practice in Italy. Ibrutinib retention rate at one-year suggests a better knowledge and expertise of hematologists in the management of ibrutinib-related toxicities that may result in an improved long-term outcome of pts with CLL.
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OBJECTIVES: During COVID-19 athletes have had games canceled, seasons postponed, and social supports lost. These changes negatively impact their motivation, and potentially identity, as athletes. We draw on self-determination theory to examine motivation in sport and its relationship with athlete identity during COVID-19. DESIGN: A cross-sectional study design was employed consisting of online quantitative surveys. METHOD: We gathered background engagement and motivation data from 115 athletes involved in organized sport. They responded to questions on basic psychological needs satisfaction (competence, relatedness, autonomy) and athlete identity. RESULTS: When reflecting on their basic psychological needs during the pandemic, most athletes considered them important. Athletes' competence and relatedness in sport were associated with social-related athlete identity, but not autonomy. Only relatedness in sport was associated with exclusivity-related social identity. CONCLUSIONS: Using a self-determination theoretical lens, our findings contribute to understanding athlete motivation and identities when sport is interrupted.
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Introduction Ibrutinib is the only once-daily Bruton's tyrosine kinase (BTK) inhibitor with significant survival benefit vs chemo- and /or immunotherapy in multiple phase 3 studies of patients (pts) with chronic lymphocytic leukemia (CLL). It has profoundly changed the treatment landscape of CLL with the longest follow-up. However, seven years (yrs) after ibrutinib was approved in Italy by regulatory agencies for CLL treatment, available data on the patterns of care of such pts in the setting of clinical practice is limited. Herein we present the first interim analysis (IA) of EVIdeNCE (ClinicalTrials.gov Identifier: NCT03720561), a multicenter, observational clinical study designed to describe the current management of pts receiving ibrutinib in real-world setting in Italy in terms of retention rate: the study's primary end point. Methods EVIDENCE 312 treatment-naïve (TN) 38% and relapsed/refractory (R/R) 62% pts with CLL according to the iwCLL diagnosis criteria observed at 39 Italian hematological institutions in the period between November 2018 and October 2019. Inclusion criteria were treatment with ibrutinib according to the European Summary of Product Characteristics as per routine clinical practice started within the previous 3 months. The purpose of this IA is to provide demographics and disease characteristics at baseline and a preliminary evaluation of ibrutinib retention rate after one year of follow-up, along with its safety profile. Results The median age of pts at the time of ibrutinib initiation was 71.0 yrs (range 41.0-89.0), with 60% ≥70 yrs, 63.2% male, and 90% with Eastern Cooperative Oncology Group (ECOG) performance 0-1. Baseline Rai stage 0-I, II, and III-IV accounted for 18.3%, 29.7% and 52.1% pts, respectively. Patients in stage IV were observed in 40% of the R/R and 27% in TN subgroup. Considering 120 pts with known mutational status, del(17p) and/or TP53 mutation were present in 50.0% of pts (TN=52.1%, R/R=48.6%), while IGHV was unmutated in 35.0% (TN=33.3% and R/R=36.15) and mutated in 15.0% (TN=14.6%, R/R=15.3%). At baseline, 62.9% of pts had comorbidities and 30.6% presented with a history of cardiovascular diseases (CVDs). A CIRS score ≥6 was observed in 28.5% of pts. The median time from CLL diagnosis to the start of ibrutinib was 5.1 yrs (TN 1.75 yrs vs R/R 7.27 yrs). At least 1 treatment-emergent adverse event (TEAE) of any grade was experienced by 70.7% of pts. Frequencies were as follows: infections (30.8%;COVID-19 infections 3.2%), arthralgia (10.8%), neutropenia (9.3%), fatigue (8.4%), diarrhea (7.7%), atrial fibrillation (7.4%;grade 3-4, 4.2%), fever (7.1%), rash (6.4%), anemia (6.1%) and hypertension (4.2%). Mild bleeding TEAEs were reported in 16.1% of pts with no major bleeding event. TEAEs were more frequent in the elderly (≥65 yrs) while no significant differences in the rate of TEAEs were recorded in TN and R/R pts (69.7% vs 71.4%, respectively). Serious TEAEs were reported in 21.9% of pts. Overall in intention to treat (ITT), 32 deaths (10%) were observed (TN=8, R/R=24). The most common causes of death were infections (3.5%) and progressive disease (PD) (1.9%). Permanent discontinuation was observed in 56 (18%) of the pts (TN=17.2%, R/R=18.7%) and it mostly occurred within the first 6 months. Main causes of discontinuation were toxicity (6.1%), PD (3.8%) or death (3.5%). Temporary interruptions (≤ 3 months without therapy and/or dose modifications) during the whole observation period occurred in 30.3% (TN=35.3%, R/R=27.2%) and 37.7% (TN=37.5%, R/R=37.8%) of pts, respectively, mainly determined by toxicity and clinical judgment. Finally, in this first IA after 17.3 months (range 1.1 - 27.0) median follow-up, the ibrutinib retention rate (calculated as the ratio between the number of patients who retained ibrutinib treatment over the total number of patients at risk) at 1-year was 81.9% [95% confidence interval (CI), 77.2% - 86.1%] with no difference between TN 83.2% (95% CI, 75.2% - 89.4%) and R/R 81.2% pts (95% CI, 74.9% - 86.4%). Conclusions EVIDENCE is the irst real-world study of ibrutinib use in CLL clinical practice in Italy. Ibrutinib retention rate at one-year suggests a better knowledge and expertise of hematologists in the management of ibrutinib-related toxicities that may result in an improved long-term outcome of pts with CLL. Disclosures: Molica: Janssen: Consultancy, Honoraria;Abbvie: Consultancy, Honoraria;Astrazeneca: Honoraria. Scarfo: Astra Zeneca: Honoraria;Abbvie: Honoraria;Janssen: Honoraria, Other: Travel grants. Murru: Abbvie: Consultancy, Honoraria, Other: travel and accommodation;Janssen: Consultancy, Honoraria. Sportoletti: AstraZeneca: Consultancy, Honoraria;Janssen: Consultancy, Honoraria;AbbVie: Consultancy, Honoraria. Frigeri: Celgene: Consultancy, Speakers Bureau;Abbvie: Speakers Bureau;Janssen: Consultancy, Speakers Bureau;Amgen: Speakers Bureau. Sanna: Janssen: Consultancy;Abbvie: Consultancy;Astra Zeneca: Consultancy. Coscia: Janssen: Honoraria, Other, Research Funding;AbbVie: Honoraria, Other;AstraZeneca: Honoraria;Gilead: Honoraria. Reda: Abbvie: Consultancy;Astra Zeneca: Consultancy;Beigene: Consultancy;Janssen: Consultancy. Tafuri: Novartis: Research Funding;Roche: Research Funding;Celgene: Research Funding. Grugnetti: Janssen: Current Employment. Magarotto: Janssen: Current Employment. Mauro: Tskeda: Consultancy, Honoraria;Gilead: Consultancy, Honoraria;Janssen: Consultancy, Honoraria, Speakers Bureau;Abbvie: Consultancy, Honoraria, Speakers Bureau;Roche: Consultancy, Honoraria;Astra Zeneca: Consultancy, Honoraria, Speakers Bureau.
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Boredom is a salient emotion experienced in postsecondary settings, and evidence reveals that it can negatively impact academic achievement and motivation. Drawing from the control-value theory (CVT) of achievement emotions (Pekrun, 2006) and the component process model of emotions (CPM; Scherer, 1984), our study examines the first phase of a multi-sequenced online boredom intervention training (BIT) program. The goal of Phase I of BIT was to increase university students' (N = 85) knowledge about boredom as a scholarly construct. Students completed four components of the Phase I BIT session, including: (a) a baseline survey and knowledge quiz, (b) a psychoeducational video, (c) a consolidation exercise, and (d) a follow-up knowledge quiz. We employed a repeated measures analysis to measure changes in knowledge after students watched the psychoeducational boredom video. Our findings reveal that students became more knowledgeable about boredom, learned something novel, and were interested in the intervention. The results are discussed in terms of the implications for research, theory, and practice.
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Boredom , Motivation , Achievement , Emotions , Humans , StudentsABSTRACT
Background: Given the multifactorial immune defect characterizing chronic lymphocytic leukemia (CLL), it appears conceivable that these patients have risk factors that increase their likelihood of complications and death from COVID-19. Aims: To evaluate incidence and severity of COVID-19 cases in a well-defined cohort of patients with CLL receiving venetoclax-based combinations. Methods: We administered a survey to a cohort of CLL treating hematologists from hematological centers in southern Italy. Participants were asked: a) to indicate whether they had offered a test for detection of COVID-19 infection (mainly nasopharyngeal swabs) only to CLL patients who reported symptoms or universally;b) to provide information on the incidence of COVID-19 infection and its severity;c) to specify reasons of possible treatment modifications. The survey was restricted to relapsed-refractory (R/R) CLL patients treated from Feb 1st to Dec 31th 2020 with time-limited venetoclax/rituximab (VR) combination as recommended by MURANO protocol (venetoclax for up to 2 years plus rituximab for the first 6 months), within their clinical practice. Results: A specific questionnaire was sent to 30 CLL hematologists, but only 26 responded to all questions. We considered suitable for the present analysis the 24 questionnaires compiled by hematologists who declared to have treated at least one patient with VR combination in the observation period. Of those, 20.8% worked in academic hospitals. Overall, the survey allowed to collect data on 124 patients who were treated with VR combination. The median number of patients treated in each center was 5 (range,1-15).COVID-19 surveillance tests consisted of viral RNA reverse transcriptase PCR (RT-PCR) on nasopharyngeal swabs. Generally, a policy of universal SARS-CoV-2 testing to be performed on patients at different time-points of therapy was used. Most patients (83/124, 66.9%) were tested before beginning the ramp-up with venetoclax;moreover 66/124 (53.2%) were regularly tested before each rituximab infusion (Fig 1).Reasons for potential change of the schedule of treatment were also investigated. The survey revealed that adherence to treatment was relatively high (70.8%). Only 29.1% physicians modified the therapeutic program mainly because of grade 3 neutropenia. Changes consisted of transient interruption of venetoclax, reduction of doses, and delay of rituximab infusion.Only 2/124 patients (1.6%) had a symptomatic RT-PCR proven diagnosis of COVID-19 infection and required hospitalization. Both patients needed oxygen therapy and admission into an intensive care unit. Of those, 1 patient who was receiving VR combination at the time of COVID infection, eventually died. The second patient developed COVID-19 infection while receiving venetoclax monotherapy (after the VR combination period). He recovered from COVID-19 infection and after 21 days of treatment interruption, he was able to restart venetoclax. Summary/Conclusion: Results of the present survey provide information, thus far lacking, on the use in real-world clinical practice of VR combination during the COVID19 pandemic in 2020. Current literature on the prevalence of COVID-19 infection in CLL, has some limitations (i.e., small size sample, heterogeneity of treatment, restriction to only the first pandemic wave);this survey, performed on a large number of CLL patients treated with VR combination only seems to provide additional information on safe management of CLL treatment during the COVID19 pandemic.
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Background: Patients with hematologic malignancies appear to have a greater risk of SARS-CoV-2 infection and severe disease due to myelosuppression;furthermore, delays in treatment of patients with hematologic malignancies, especially those with acute leukemia planned for chemotherapy or transplantation, are associated with a risk of disease progression. To date, some societies recommend that chemotherapy should generally not be started until COVID-19 symptoms have completely resolved and viral testing becomes negative. However, implications of the aforementioned recommendations remain uncertain in routine clinical practice, and data on COVID-19 in patients with hematologic malignancies are still limited. Aims: We carried out a single-center analysis of acute leukemia inpatients who developed COVID-19 during the last year. Methods: Since February 2020 to February 2021, a total of 310 Hospitalizations,63 adult patients were admitted in our Center for treatment of hematologic malignancies. The indication for admission was acute myeloid leukemia (AML) in 50 (30%) patients, acute lymphoblastic leukemia (ALL) in4 (8%), lymphoma in 54 (33%), myeloma in4 (8%), other 31 (19%). Diagnosis of SARS-CoV-2 infection was based on virus detection by real-time polymerase chain reaction (SARS-CoV-2 E-gene RT-PCR) in respiratory tract specimens. Standard preventive measures for SARS-CoV-2 infection control were applied to all patients care, accordance with National disease control and prevention guidelines. Results: Ten (6%) patients tested positive for SARS-CoV-2 via PCR in a unique Covid-19 outbreak during hospitalization stay, and they were immediately transferred to Covid Infectious Unit. All these patients, were affected by Acute Leukemia (8 pts AML, 2 pts ALL ph negative), the majority of them was in peak of cytopenia at the Covid-19 infection time. Nine patients had been treated with intensive chemotherapy before SARS-CoV-2 confirmation. At SARS-CoV-2 diagnosis, only one patient had untreated, newly diagnosed AML;3 patients had refractory/relapsed AML. One patient was in complete remission with incomplete hematologic recovery (CRi). Deep vein thrombosis complicated by pulmonary embolism and interstitial pneumonia was observed in a patients despite anticoagulation and in thrombocytopenia. After SARS-CoV-2 infection, no leukemia-specific treatment was adjusted. Three patients (30%) died due to severe acute respiratory distress syndrome (ARDS) despite extracorporeal membrane oxygenation (ECMO) in deep aplasia, all of them was in refractory disease. Seven patients delayed in chemotherapy treatment for a media of 34 days;chemotherapy started until COVID-19 symptoms have completely resolved and two viral testing becomes negative. However, these patients are still alive and maintained their complete remission, remaining for long-time negative for SARS-CoV-2. One patient underwent to bone marrow transplantation Summary/Conclusion: Our findings support the vulnerability of patients with hematologic malignancies in the COVID-19 pandemic, and we reported a high COVID-19 infection mortality of 30%, in accordance with other hematological case series. However, deaths owing to Covid-19 were observed in patients in disease leukemia progression;furthermore, our recovered COVID-19 leukemia patients remained negative for SARSCoV- 2 after delivery of chemotherapy, and underwent to their following chemotherapy and allo-BMT program without any other complications.
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During the northern hemisphere Winter 2020 academic term, university students had to adjust to remote learning in response to the COVID-19 pandemic. This abrupt change provided a unique opportunity to examine students' motivation, engagement and perceptions of success and cheating under two learning conditions, namely traditional and remote. We used a single survey to collect retrospective self-report data from a convenience sample of Canadian undergraduate students (n = 98) about their motivation, engagement and perceptions of success and cheating before COVID-19 and then in remote learning. Students' achievement goals, engagement and perceptions of success all significantly decreased, while their perceptions of cheating increased. Moreover, we used regression analyses to examine associations amongst achievement goals and engagement, perceptions of success and cheating concerns. Mastery-approach goals were positively associated with more engagement and higher perceptions of success. Achievement goals were unrelated to cheating. Students in large classes and who were originally concerned about cheating became more concerned about cheating in remote learning conditions. Our study provides information to researchers and instructors about how achievement goals relate to student outcomes across learning conditions. By extension, we provide timely recommendations for instructors as they continue to wrestle with how to deliver their courses during the COVID-19 pandemic.