scholarly journals A Sex-Informed Approach to Improve Prognostication and Personalized Decision-Making Process in Myelodysplastic Syndromes. a European Study of 11.878 Patients

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 23-24
Author(s):  
Giulia Maggioni ◽  
Erica Travaglino ◽  
Ana Alfonso Pierola ◽  
Jennifer Kaivers ◽  
Montserrat Arnan ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Disease Stage ◽  
Decision Making Process ◽  
Early Disease ◽  
Prognostic Information ◽  
Advisory Committees ◽  
Female Patients ◽  
Prognostic Effect ◽  
Early Disease Stage

Introduction Sex represents a major source of diversity among patients in terms of pathophysiology, clinical presentation, prognosis and response to therapy, and therefore sex (gender)-informed medicine is becoming a new paradigm to refine clinical decision making process in different human diseases. Myelodysplastic syndromes (MDS) are heterogeneous disease characterized by ineffective hematopoiesis and risk of leukemic evolution. We aimed to study clinical effect of sex in MDS as a basis to improve patient prognostication and personalized treatment. Material and Methods We analysed three MDS populations from disease-specific registries (Italian registry n=3015, Dusseldorf registry, n=1185 and Spanish registry, n=7678). Results We first analysed the association of sex with clinical and biological disease-specific features. These analyses were conducted on Italian MDS cohort. Considering WHO categories, female patients showed higher prevalence of single lineage dysplasia and MDS with del(5q), while males were characterized by higher frequency of multilineage dysplasia and excess blasts (P<.001). Considering cytogenetic abnormalities, an increased frequency of del(5q) in female patients was observed (P<.001). We analysed mutations in 47 MDS-associated genes. Males presented higher prevalence of mutations with respect to females (82.2% vs. 76.2%, P<.001), with higher prevalence of co-mutations. Considering specific gene pathways, splicing factors mutations were reported more frequently in males vs. females (66% vs. 56%, P<.001). Focusing on MDS with ring sideroblasts (MDS-RS), we noticed a significant different distribution of splicing factor mutations according to sex: SF3B1 was mutated in large majority of female patients (95% of mutated cases), while SRSF2 and ZRSR2 mutations accounts for a significant proportion (26%) of mutated cases in males. In addition, males showed higher prevalence of mutations in DNA methylation genes (P<.001), while tumor suppressor genes (TP53) were more frequently mutated in female patients. Clustering analysis showed specific co-mutation patterns in splicing and DNA methylation genes according to sex. Overall survival was significantly worse for male vs. female patients (P<.001). In a multivariable analysis including age, neutrophils, hemoglobin and platelet counts, percentage of marrow blasts and cytogenetics as covariate, sex showed an independent effect on probability of survival (HR for female vs. male patients 0.56, P=.012). The prognostic effect of sex was observed in very-low, low and intermediate risk category according to IPSS-R (Table 1). The independent prognostic effect of sex was confirmed in two independent populations (Dusseldorf and Spanish registries). Competitive risk analysis showed higher prevalence of non-leukemic vs. leukemic deaths (P<.001) in patients with early disease stage. In these patients, we observed a higher prevalence of cardiac comorbidity/deaths in males vs. females (P<.001 and P=.005, respectively). Moreover, the risk of non-leukemic death was higher in males vs. females especially when hemoglobin levels were <10 g/dl. These results suggest that in MDS patients, sex may capture prognostic information on the detrimental interactions between anemia and cardiac comorbidity. As a final step we aimed to integrate the prognostic value of sex into currently available prognostic systems (IPSS-R). We used random effects Cox proportional-hazards multistate modelling for developing an innovative personalized prognostic model ("Sex and age-adjusted IPSS-R", IPSS-RAS). All the three study populations were included (n=11.878). The predicted and observed outcomes correlate well in internal cross-validation. IPSS-RAS substantially improved predictive accuracy of original IPSS-R (concordance 0.68 vs. 0.62), especially in patients with early disease stage. Interestingly, demographic factors (age and sex) accounted for >30% of whole prognostic power. Conclusion In MDS, sex captures additional prognostic information at individual patient level, possibly reflecting a different molecular background and, most importantly, a sex-specific interaction between disease-related factors and comorbidity. Our results strengthen the rationale to include sex in personalized prognostic assessment in these diseases. Table 1 Disclosures Voso: Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Passamonti:Roche: Other: Support of parent study and funding of editorial support; Novartis: Speakers Bureau; BMS: Speakers Bureau. Santoro:Bristol-Myers Squibb, SERVIER, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Sanofi, ArQule: Consultancy; Takeda, Roche, Abbvie, Amgen, Celgene, AstraZeneca, ArQule, Lilly, Sandoz, Novartis, Bristol-Myers Squibb, Servier, Gilead Sciences, Pfizer, Eisai, Bayer, MSD: Speakers Bureau; Takeda, Roche, Abbvie, Amgen, Celgene, AstraZeneca, ArQule, Lilly, Sandoz, Novartis, Bristol-Myers Squibb, Servier, Gilead Sciences, Pfizer, Eisai, Bayer, MSD: Speakers Bureau; Arqule, Sanofi: Consultancy; Bristol-Myers Squibb, SERVIER, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Sanofi, ArQule: Consultancy, Speakers Bureau; Bristol-Myers Squibb, SERVIER, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Sanofi, ArQule: Consultancy; Bristol Myers Squibb, Servier, Gilead, Pfizer, Eisai, Bayer, MSD: Membership on an entity's Board of Directors or advisory committees. Santini:Menarini: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Acceleron: Consultancy; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria; Johnson & Johnson: Honoraria. Sanz:Takeda Pharmaceutical Ltd.: Membership on an entity's Board of Directors or advisory committees; LaHoffman Roche Ltd.: Membership on an entity's Board of Directors or advisory committees; Abbvie Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Helsinn: Membership on an entity's Board of Directors or advisory committees. Diez-Campelo:Celgene BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Efficacy Outcomes of Treatments for Double Relapsed/Refractory Follicular Lymphoma (R/R FL): A Systematic Literature Review

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 42-43
Author(s):  
Brad S. Kahl ◽  
Anik R. Patel ◽  
Omer Zaidi ◽  
Sonya J. Snedecor ◽  
Anna G. Purdum
Keyword(s):  
Clinical Trials ◽  
Follicular Lymphoma ◽  
Board Of Directors ◽  
Clinical Data ◽  
Research Funding ◽  
Treatment Options ◽  
Unmet Need ◽  
Progression Free Survival ◽  
Disease Stage ◽  
Advisory Committees

ABSTRACT Introduction: Patients with indolent non-Hodgkin lymphomas (iNHL), including follicular lymphoma (FL), have high response to first-line treatment. However, retreatment is often required when relapses occur, and those with multiple relapses represent a patient population with an unmet need for effective treatment. Clinical data for several treatment options exist for the general relapsed and refractory (R/R) population; however, there are relatively fewer data specific to FL patients with ≥2 lines of prior treatment. This work systematically identified the available efficacy data in the double R/R FL population. Methods: The MEDLINE and EMBASE databases were searched through February 10, 2020. Studies were limited to interventional clinical trials of R/R FL patients (or mixed histologies with a predominance of FL) and articles published in English. Studies also must have reported one or more efficacy measures, such as overall response rate (ORR), complete response (CR), duration of response (DoR), time to next treatment (TTNT), progression-free survival (PFS), and overall survival (OS). Potential interventions of interest were lenalidomide ± rituximab (R), duvelisib, ibrutinib, venetoclax, polatuzumab vedotin + R, obinutuzumab, copanlisib, umbralisib, idelalisib, and tazemetostat. Results: Of 35 publications examining treatment outcomes in R/R FL patients, only 14 (representing 5 unique clinical trials) were specific to the ≥ 2-line population. These trials were: CHRONOS Part B (copanlisib), DAWN (ibrutinib), DELTA (idelalisib), DYNAMO (duvelisib), and Morschhauser et al. 2019 (tazemetostat) and included a total of 605 participants. All studies used similar inclusion criteria, and patients included were similar in age (median 62-65), disease stage (III/IV), and ECOG score (0-2). Patients in the CHRONOS study had a median number of prior treatments of 2, whereas those in the DELTA study had 5. ORR ranged from 21% (ibrutinib) to 59% (copanlisib) (Table). The DoR ranged from 8.3 months in tazemetostat patients with EZH2 gene mutation to 19.4 months for ibrutinib. PFS ranged from 5.7 months in tazemetostat patients with wild-type EZH2 to 11.2 months for copanlisib. Median TTNT was only reported in the DAWN study (16 months). Conclusions: Very few clinical data exist reporting efficacy outcomes specific to the double R/R FL population. The limited data indicate that current treatments do not produce durable responses for most double R/R FL patients, demonstrating an unmet need. Further research is needed to fully understand the efficacy and safety of other potential interventions for this population. Disclosures Kahl: Genentech:Consultancy;Pharmacyclics LLC:Consultancy;AstraZeneca Pharmaceuticals LP:Consultancy, Membership on an entity's Board of Directors or advisory committees;ADC Therapeutics:Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Celgene Corporation:Consultancy;AbbVie:Consultancy;Roche Laboratories Inc:Consultancy;BeiGene:Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Janssen:Consultancy, Membership on an entity's Board of Directors or advisory committees;Acerta:Consultancy, Research Funding.Patel:Kite, a Gilead Company:Current Employment.Zaidi:BMS:Consultancy.Snedecor:Pharmerit - an OPEN Health Company:Other: Employment at consultancy paid by Kite Pharma to conduct this work.Purdum:Kite, a Gilead Company:Current Employment.

scholarly journals Pathologic Misdiagnosis in Children with Suspected Burkitt Lymphoma Associated with Early Mortality

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2271-2271
Author(s):  
Chloe Stiggelbout ◽  
Megan Real-Hall ◽  
Innocent Mutyaba ◽  
Elizabeth M Krantz ◽  
Scott Adams ◽  
...  
Keyword(s):  
Sample Size ◽  
Board Of Directors ◽  
Burkitt Lymphoma ◽  
Research Funding ◽  
Early Mortality ◽  
Disease Stage ◽  
Advanced Stage ◽  
Advisory Committees ◽  
Kaplan Meier ◽  
Stage Disease

Abstract INTRODUCTION Burkitt lymphoma (BL) is one of the most common childhood cancers across sub-Saharan Africa (Walusansa et. al, 2012). Unfortunately, the one-year survival rate of children with BL treated in low- and middle- income countries (LMICs) remains low, compared to higher-resource settings (Howard et al., 2008, Stanley et al., 2016, Buckle et al., 2016). Factors in LMICs contributing to this disparity include inability to give high-dose chemotherapy, lack of supportive care measures, and treatment abandonment (Gopal, 2018). The impact of diagnostic inaccuracies on BL outcome has not been well-studied to date. PURPOSE To determine the frequency and impact of an incorrect histopathologic diagnosis in children with suspected BL presenting to the Uganda Cancer Institute (UCI). METHODS Study Design and Participants -A sample of subjects with available tissue biopsies was selected from a cohort of children presenting to the UCI with suspected BL between July 2012 and July 2017. Laboratory Methods - Formalin fixed, paraffin embedded (FFPE) tumor blocks were obtained from local Ugandan pathology laboratories and sectioned in a single, central Ugandan histology lab. Slides were then shipped to a US-based reference laboratory for front-line evaluation by Hematoxylin and Eosin (H&E) staining, by intentionally streamlined immunohistochemistry (IHC) for CD20, c-Myc, and TdT detection, and by EBER-1 in situ hybridization (ISH) for EBV detection. A diagnosis of BL required the expected H&E appearance and prominent tumor expression of CD20, c-Myc, and EBER-1, with no significant TdT expression. For equivocal cases, additional CD10, CD21, bcl-2, and Ki67 IHC could be employed. Misdiagnosis Definition - A discrepancy between the pathologic diagnosis confirmed by IHC/ISH at the US-based laboratory, and the diagnosis that determined treatment in Uganda. Clinical and Statistical Analysis - Advanced disease stage included Ziegler stage C, D, or AR based on physical exam. Kaplan-Meier and Cox regression analysis were applied to evaluate survival. RESULTS We enrolled 97 participants of with a median age of 7 (interquartile range (IQR) 4-10); 69% were male, 47% had ECOG status 0-1, and 48% had advanced stage disease (though 22% had missing staging information - Table 1). The majority of patients had facial involvement, while less than half of the evaluable patients had abdominal involvement. Twenty percent of biopsies (19/97) were misdiagnosed. Median follow-up time was 7.1 (IQR 1-12) months, during which 68% (13/19) of misdiagnosed patients died, compared to 49% (38/78) of correctly diagnosed patients. The Kaplan Meier estimate of survival among the entire cohort was 42% (95%CI 31-52%); those with and without a misdiagnosis had survivals of 20% (95% CI 5-42%) and 46% (95% CI 34-57%), respectively (Figure 1). The logrank value comparing survival among those with and without a misdiagnosis was 0.0047. CONCLUSIONS BL diagnosis remains challenging in resource-limited areas, with a high misdiagnosis rate of 20% in this cohort. Misdiagnosed patients tended to be younger and to have more advanced stage disease. We observed a significant positive association between misdiagnosis and early mortality. Misdiagnosis likely contributes to poorer BL survival in low-resource settings by increasing the chance of treatment for the wrong tumor type. SIGNIFICANCE Study limitations include relatively small sample size and the potential for selection bias among patients who had tissues samples available; however, the 12-month survival of all patients diagnosed with BL at the UCI during the study period was around 55%, and not markedly different from the 42% seen here. Next steps include a repeat study with a larger sample size. Finally, our novel IHC/ISH diagnostic algorithm, requiring 6 total slides (including 1 control slide to assess RNA quality), worked with high sensitivity and specificity, and will be described separately. Disclosures Real-Hall: Phenopath Laboratories: Employment. Adams:Burkitt Lymphoma Fund for Africa: Membership on an entity's Board of Directors or advisory committees, Research Funding. Uldrick:Celgene: Research Funding; Celgene: Patents & Royalties: 10,001,483 B2; Merck: Research Funding. Casper:Janssen: Consultancy, Research Funding; Up to Date: Patents & Royalties; TempTime: Consultancy, Other: Travel, Accommodation, Expenses; GSK: Other: Travel, Accommodation, Expenses; Roche: Consultancy, Other: Travel, Accommodation, Expenses. McGoldrick:Burkitt Lymphoma Fund for Africa: Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Employment. Kussick:Phenopath Laboratories: Employment, Equity Ownership.

scholarly journals Does Addition of Rituximab (R) to BEAM Conditioning Improve Outcomes of Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Undergoing Autologous Hematopoietic Cell Transplantation (auto-HCT)?

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 785-785
Author(s):  
Deepa Jagadeesh ◽  
Navneet S. Majhail ◽  
He Yizeng ◽  
Kwang Woo Ahn ◽  
Carlos Litovich ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Cumulative Incidence ◽  
Research Funding ◽  
B Cell Lymphoma ◽  
Older Age ◽  
Disease Stage ◽  
Karnofsky Performance Score ◽  
Advisory Committees ◽  
Significant Difference ◽  
The Impact

Introduction: Rituximab-based high-dose therapy (HDT) is frequently prescribed to DLBCL patients (pts) undergoing auto-HCT. However data supporting the benefit of adding R to auto-HCT conditioning are not available. Herein, we report the impact of R-based conditioning on auto-HCT outcomes of DLBCL pts. Methods: Using the Center for International Blood and Marrow Transplant Research registry, 862 adult (≥18 years) DLBCL pts undergoing auto-HCT, between 2003-2017 were included. Analysis was limited to pts receiving BEAM (BCNU, etoposide, cytarabine, melphalan)-based HDT, as R was infrequently used with non-BEAM conditioning regimens. All pts received R-containing chemoimmunotherapy in the frontline setting and had chemosensitive disease prior to HCT. Early chemoimmunotherapy failure (ECitF) was defined as not achieving a complete remission (CR) after frontline chemoimmunotherapy or relapsing within 1 year of initial diagnosis. Primary outcome was overall survival (OS). Secondary outcomes included non-relapse mortality (NRM), relapse, progression-free survival (PFS) and infectious complications within 100 days post-HCT. Results: The study cohort was divided into 2 groups; BEAM (n=667) and R-BEAM (n=195). The baseline characteristics of the 2 cohorts were comparable including age at auto-HCT, disease stage, Karnofsky performance score, extranodal involvement, time from diagnosis to auto-HCT, number of prior therapies, remission status, and ECitF. However, significantly more R-BEAM cohort patients received R as part of last therapy line before auto-HCT (75% vs. 86%; P=0.001). Median follow-up of survivors was 48 (range 1-171) and 64 (range 3-142) months in the BEAM and R-BEAM cohorts, respectively. On univariate analysis, the 4 year cumulative incidence of relapse (41% vs 44%), NRM (11% vs 9%), PFS (48% vs 47%; Figure 1) and OS (58% vs 61%; Figure 2) were similar in the R-BEAM and BEAM groups, respectively (Table 1). On multivariate analysis, no significant difference was seen in OS (HR 0.81; 95% CI 0.81-1.31; P=0.83) or PFS (HR 0.94; 95% CI 0.76-1.18; P=0.61) (Table 1) between the two cohorts. Addition of R had no impact on risk of relapse (HR 0.83; 95% CI 0.65-1.07; P=0.15) or NRM (HR 1.43; 95% CI 0.909-2.26; P=0.12). Variables independently associated with lower OS included older age (HR 3.05; 95% CI 1.81-5.13; P<0.001), not being in CR at auto-HCT (HR 1.67, 95% CI 1.39-2.07; P<0.001) and presence of ECitF (HR 1.52, 95% CI 0.54-3.26; P<0.001). Older age (HR 2.26, 95% CI 1.48-3.45; P<0.0002) and not being in CR at auto-HCT (HR 1.78, CI 1.47-2.14; P<0.0001) were also associated with inferior PFS. There was no significant difference in the 100-day cumulative incidence of bacterial, viral or fungal infections between the two cohorts. Disease relapse was the main cause of death in both BEAM and R-BEAM cohorts (66% vs 55%). Conclusion: In this large registry analysis of DLBCL pts undergoing auto-HCT, adding R to BEAM conditioning had no impact on transplantation outcomes. Older age, absence of CR and ECitF were associated with inferior survival. Disclosures Majhail: Mallinckrodt: Honoraria; Incyte: Consultancy; Nkarta: Consultancy; Anthem, Inc.: Consultancy; Atara Bio: Consultancy. Sureda:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support; Gilead: Honoraria; Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Speakers Bureau; Novartis: Honoraria; BMS: Honoraria; Roche: Honoraria; Sanofi: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kharfan-Dabaja:Daiichi Sankyo: Consultancy; Pharmacyclics: Consultancy. Hamadani:ADC Therapeutics: Consultancy, Research Funding; Merck: Research Funding; Takeda: Research Funding; Pharmacyclics: Consultancy; Celgene: Consultancy; Medimmune: Consultancy, Research Funding; Janssen: Consultancy; Otsuka: Research Funding; Sanofi Genzyme: Research Funding, Speakers Bureau.

Validation of a Flow Cytometric Scoring System for the Prognostication of the Myelodysplastic Syndromes: a Retrospective Cohort Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4012-4012
Author(s):  
Canan Alhan ◽  
Theresia M. Westers ◽  
Claudia Cali ◽  
Gert J. Ossenkoppele ◽  
Arjan A. Van de Loosdrecht
Keyword(s):  
Healthy Volunteers ◽  
Board Of Directors ◽  
Myelodysplastic Syndromes ◽  
Scoring System ◽  
Research Funding ◽  
Classification Systems ◽  
Prognostic Information ◽  
Advisory Committees ◽  
Flow Cytometric ◽  
Myeloid Progenitors

Abstract Abstract 4012 The myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell disorders, characterized by cytopenia(s), dysplasia and a propensity to evolve into acute myeloid leukemia. The International Prognostic Scoring System (IPSS) and WHO-based prognostic scoring system provide prognostic information. However, even if patients are allocated in the same risk category their clinical course remains heterogeneous. Recent developments in the treatment of MDS require refinement of prognostication and identification of patients who might benefit from treatment with potentially disease modifying agents such as lenalidomide or azacitidine. Flow cytometry (FC) is emerging as a valuable technique for the diagnosis and prognosis of MDS. Recently, we demonstrated that flow cytometric analysis of BM in low and int-1 risk MDS is instrumental to identify clinically relevant subgroups. (Westers et al, Blood 2010) Previously, it was reported that a flow cytometric scoring system (FCSS) is predictive for worse outcome in MDS. (Wells et al, Blood 2003, van de Loosdrecht et al, Blood 2008) The FCSS is a scoring system that allows for a numerical display of immunophenotypic aberrancies in the (im)mature myelo-monocytic lineage. Scores are generated by enumerating abnormalities; a high score reflects a high number of aberrancies. The current study aimed to validate the FCSS for identification of prognostic subgroups in MDS. We analyzed aberrancies in (im)mature myelo-monocytic cells by FC in BM of 102 MDS patients, including 48 MDS patients from the previous cohort. The diagnoses according to WHO 2001 classification were RA(RS) n=19, RCMD(RS) n=54, RAEB-1 n=11, RAEB-2 n=13, MDS-U n=5 and also age-matched healthy volunteers (n=39) were included. The median age of MDS patients was 66 and of healthy volunteers 57. The FCSS in RA(RS) (median=3, range 1–6) patients was significantly higher compared with healthy controls (median=1, range 0–2, p<0.001). In contrast to our previous results the FCSS for RA(RS) and RCMD(RS) patients did not differ. This is a remarkable finding, since by morphology RA(RS) patients have unilineage dysplasia, in contrast to flow cytometric findings, where 84% (16/19) of the RA(RS) patients had two or more aberrancies in the (im)mature myelomonocytic compartment. The FCSS was higher in RAEB-1 (median=6, range 2–7) and RAEB-2 (median=6, range 4–8) compared with RCMD(RS) (median=3, range 0–6, p=0.02 and p<0.0001, respectively). Overall, the FCSS correlated significantly with WHO 2001 classification (p<0.0001). The FCSS showed a significant correlation with IPSS categories low, int-1, int-2 and high (p<0.0001). Remarkably, the FCSS was not correlated with cytogenetic risk categories low, intermediate and poor. The new German-Austrian Cytogenetic Prognostic Scoring System for MDS was also not correlated with the FCSS. This indicates that the FCSS and cytogenetics might provide separate prognostic information in MDS. Neutrophil granularity corresponding with side scatter by FC was significantly decreased in MDS patients compared with healthy volunteers (p<0.0001). In the RA(RS) and RCMD(RS) category, 40% (29/73) of patients expressed an aberrant marker such as CD5, CD7 and/or CD56 on myeloid progenitors. Transfusion data was available of 51 patients. Interestingly, the majority of MDS patients who were transfusion dependent or progressive, had aberrant expression of CD5, CD7 and/or CD56 on myeloid progenitors compared with MDS patients without aberrant marker expression (64% (16/25) vs 31% (8/26), respectively p=0.04). When the cumulative amount of all aberrancies in the (im)mature myelo-moncytic cells were taken into account, transfusion dependent patients had significantly more aberrancies than transfusion independent MDS patients, (median 6.5 vs 4, respectively, p=0.006). In conclusion, we here confirmed our previous findings in a larger cohort. The majority of RA(RS) patients already has multilineage dysplasia as detected by FC, which might be of prognostic relevance. Although the FCSS correlates with current prognostic systems, a striking heterogeneity remains within prognostic subgroups. Therefore, the FCSS and detection of aberrant myeloid progenitors can provide refined prognostication by identification of patients at risk for transfusion dependency and adverse clinical outcome, independent of current classification systems. Disclosures: Ossenkoppele: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Van de Loosdrecht:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Immunoparesis Recovery As Predictor Marker of Progression after Autologous Stem Cell Transplantation in Multiple Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4356-4356 ◽  
Author(s):  
Veronica Gonzalez De La Calle ◽  
Eduardo Sobejano ◽  
Julio Davila ◽  
Enrique M Ocio ◽  
Noemi Puig ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Research Funding ◽  
B Lymphocyte ◽  
Disease Stage ◽  
Advisory Committees

Abstract BACKGROUND High dose therapy followed by autologous stem cell transplantation (ASCT) remains the standard of care, especially in Europe, for young and eligible multiple myeloma patients (usually younger than 65 years old). Immunoparesis is defined as a reduction (below the lower normal limit) in the levels of 1 or 2 uninvolved immunoglobulins (Ig) and it is related to a reversible suppression of B lymphocytes that correlates inversely with disease stage. B Lymphocyte reconstitution begins at 3 months after ASCT, with maximum B lymphocyte levels at 1 year after ASCT. AIMS The goal of the present study was to investigate the role of the immunoparesis recovery after ASCT as predictor of relapse or progression in multiple myeloma (MM). METHODS We reviewed medical records of MM patients who underwent to ASCT at University Hospital of Salamanca between 1992 and 2013. The primary endpoint was time to relapse or progression from ASCT. Ig (Ig G, Ig A e Ig M) were collected at the time of diagnosis, before ASCT, every 3 months during the first year after ASCT, and every year up to 5 years after ASCT among eligible patients until the relapse or disease progression. RESULTS 106 multiple myeloma patients who underwent ASCT were included in the analysis. Conventional chemotherapy was administered as induction regimen in 69 patients (65%), whereas novel agents were used in 37 patients (35%). Most patients had immunoparesis at diagnosis (91%) and at the moment of ASCT as well (94%). After a median follow-up of 62 months, median time to progression or relapse (TTP) from ASCT was 31 months (95 % CI: 24.1 - 37.1 months). MM patients with immunoparesis 1 year after ASCT had a significantly shorter median TTP as compared with patients without immunoparesis (33.5 months vs 94.2 months; HR: 2.14, 95% CI: 1.13-4.05; p=0.019). In the group of patients with reduction of both Igs, median TTP was slightly inferior than in the group with reduction of only one of them(33.5 vs 36.4 months, p=0.03). Presence of ISS 3, high-risk cytogenetics at diagnosis, less than partial response achieved before and three months after ASCT were also identified as predictors of progression. Multivariate analysis selected immunoparesis 1 year after ASCT as an independent variable for relapse or progression (HR: 5.97, 95% CI: 1.63-21.88; P=0.007). CONCLUSIONS The lack of immunoparesis recovery at 1 year after ASCT in MM patients is associated with significantly higher risk of relapse or progression and this group of patients could potentially benefit of continuous treatment after ASCT to enhance the immune recovery. Disclosures Ocio: Array BioPharma: Consultancy, Research Funding; Celgene: Consultancy, Honoraria; Amgen/Onyx: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy; Mundipharma: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; MSD: Research Funding; Pharmamar: Consultancy, Research Funding; Janssen: Honoraria. Puig:The Binding Site: Consultancy; Janssen: Consultancy. Mateos:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Onyx: Consultancy; BMS: Consultancy; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Outcomes for Elderly Patients (pts) with Follicular Lymphoma (FL) Using Individual Patient Data (IPD) from 5922 Pts in 18 Randomized Controlled Trials (RCTs): a Follicular Lymphoma Analysis of Surrogate Hypothesis (FLASH) Group Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1102-1102 ◽  
Author(s):  
Christopher Flowers ◽  
Fang-Shu Ou ◽  
Qian Shi ◽  
Eva Hoster ◽  
Bruce A. Peterson ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Board Of Directors ◽  
Research Funding ◽  
Regression Models ◽  
Age Groups ◽  
Early Disease ◽  
Advisory Committees ◽  
Randomized Controlled ◽  
Disease Outcomes ◽  
Ecog Ps

Abstract Background: Limited data exist to describe the clinical features and outcomes for elderly pts with FL. The FLASH group performed a prospectively planned pooled analysis of IPD from first-line RCTs and examined associations between age (<= 70 vs. > 70 years), clinical characteristics and FL outcomes. Methods: We identified 18 randomized controlled multicenter clinical trials in the FLASH database which enrolled elderly pts (> 70 yrs). From these 18 studies, 5922 previously untreated FL pts were included for this analysis. Complete response (CR) at 24 and 30 months were defined as whether the pt achieved and remains in CR at 24 months and 30 months after initiation of induction treatment. PFS24 is defined as proportion of pts progression-free and alive at 24 months post-randomization. Time to progression (TTP) and overall survival (OS) were defined as time from randomization to the date of progression (censoring for death without progression) and date of death due to any cause, respectively. Progression-free survival (PFS) was defined as time from randomization to the date of progression or death, due to any cause, whichever comes first. Non-lymphoma death was defined as death without prior progression. Early disease outcomes, i.e. CR24, CR30, and PFS24 were primary outcomes; secondary outcomes were TTP, OS, and PFS. For time-to-event outcomes, Kaplan-Meier method and log-rank test were used for univariate estimation and comparison; stratified Cox proportional hazard modeling was used for multivariable analyses. Cumulative incidence methods were used to model PFS while treating disease progression as the primary event of interest and non-lymphoma death as a competing risk. For binary outcomes, multivariable logistic regression was used to estimate the association between age groups and outcomes. Variable adjusted in the regression models are FLIPI score without the age component, ECOG performance status (>= 2 vs < 2), and rituximab use. Results: Among 5922 previously untreated FL pts from 18 RCTs, 63% (n = 3728) were <= 60, 28% (n = 1652) 61-70, and 9% (n = 542) > 70 yrs. Pts age > 70 (vs. <= 70) more commonly had elevated LDH (42% vs 36%, p = 0.02), hemoglobin < 12 g/dL (27% vs 19%, p < 0.0001), ECOG PS >= 2 (8.8% vs 5.0%, p = 0.0004), and elevated β2-microglobulin (68% vs 49%, p < 0.001), less often had > 4 lymph nodes involved (54% vs 65%, p < 0.001), and had similar FLIPI scores without age component (p = 0.17). There were no significant differences between groups in: Ann Arbor stage (94% vs 95% stage III/IV) or rituximab use (62% vs 58%). Median survival follow-up was 5.6 yrs. Pts > 70 yrs did not differ from pts <= 70 in rates of CR24 (27% vs 30%, p=0.32), CR30 (29% vs 31%, p=0.55) or PFS24 (63% vs. 67%, p=0.10). Median TTP was 3.8 and 4.0 years for pts > 70 and <= 70, respectively (HR=1.08, 95% CI 0.96-1.23, p=0.20). With a median OS of 14.6 years for all pts, median OS was 7.4 and 15.7 years for pts > 70 and <= 70, respectively (HR=2.35, 95% CI=2.03-2.73, p<0.001). PFS was statistically significantly different but clinically similar at median 3.1 and 3.8 years for pts > 70 and <= 70, respectively (HR=1.26, 95% CI =1.12-1.41, p<0.001). Further investigation showed the difference in PFS was due to higher incidence of non-lymphoma death in pts > 70 with no difference in disease progression (Figure). In regression models, adjusting for rituximab use, ECOG PS >= 2, and FLIPI score without the age component, age > 70 was a significant predictor of OS and PFS (due to higher incidence of non-lymphoma death), but not PFS24, CR24 or CR30 (Table). Conclusions: FL pts > 70 yrs treated on trials have similar early disease outcomes to younger patients. There is no disease-specific outcome difference between age groups. Age alone should not disqualify patients from standard treatments or RCTs. Disclosures Flowers: Genentech: Consultancy, Research Funding; NIH: Research Funding; Mayo Clinic: Research Funding; TG Therapeutics: Research Funding; Millenium/Takeda: Research Funding; ECOG: Research Funding; Acerta: Research Funding; Pharmacyclics, LLC, an AbbVie Company: Research Funding; Roche: Consultancy, Research Funding; AbbVie: Research Funding; Infinity: Research Funding; Gilead: Consultancy, Research Funding. Ou:Mayo Clinic: Employment. Shi:Mayo Clinic: Employment. Hochster:Genentech: Consultancy, Other: Consultancy fees for advisory boards for GI cancer and bevacizumab with amounts within Yale University de minims guidelines. Brice:Roche: Honoraria; Takeda Pharmaceuticals International Co.: Honoraria, Research Funding; Bristol Myers-Squibb: Honoraria; Gilead: Honoraria; Seattle Genetics: Research Funding. Hiddemann:Roche: Other: Grants; Roche: Membership on an entity's Board of Directors or advisory committees; Genentech: Other: Grants. Marcus:Takeda: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau. Kimby:Abbvie: Consultancy, Honoraria; Jansen: Consultancy, Honoraria; Celgene: Honoraria; Baxalta: Consultancy; Gilead: Honoraria. Herold:Gilead: Other: Personal fees from member advisory board; Celgene: Honoraria; Genentech: Other: Grants; Roche: Honoraria, Other: Grants. De Bedout:Celgene: Employment. Nielsen:Hoffmann-La Roche: Employment. Morschhauser:Roche: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Gilead Sciences: Consultancy, Honoraria; Janssen: Honoraria. Rummel:Mundipharma GmbH: Other: Personal fees, Research Funding; Roche Pharma AG: Other: Personal fees, Research Funding. Vitolo:Gilead: Other: Honoraria for lectures; Takeda: Other: Honoraria for lectures; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Honoraria for lectures; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Honoraria for lectures. Salles:Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Gilead: Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Roche/Genentech: Consultancy, Honoraria, Research Funding; Mundipharma: Honoraria. Sargent:Celgene: Research Funding.

scholarly journals Full Dose or Reduced Dose Melphalan (MEL) for Autologous Stem Cell Transplantation (ASCT) in Multiple Myeloma (MM): A Single Center Analysis on 187 Consecutive Patients

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4625-4625
Author(s):  
Annamaria Brioli ◽  
vom Hofe Felix ◽  
Lars-Olof Mügge ◽  
Sebastian Scholl ◽  
Inken Hilgendorf ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Conditioning Regimen ◽  
Disease Stage ◽  
Induction Treatment ◽  
First Line ◽  
Advisory Committees ◽  
Full Dose ◽  
Reduced Dose ◽  
Support Research

Abstract Introduction MEL at the dose of 200 mg/m2 (MEL200) is considered the standard conditioning regimen before ASCT in MM patients (pts). Lower doses of 140 mg/m2 (MEL140) or 100 mg/m2 (MEL100) are used when toxicity is a concern. Whether these lower doses are equally effective is still a matter of debate and available data are conflicting. Aims and Methods To compare full dose with reduced dose MEL, we performed a retrospective analysis on MM pts in all disease stages treated at Jena University Hospital between 2003 and 2017. Statistical analysis included descriptive statistics and Cox regression. Progression free survival (PFS) and overall survival (OS) were calculated from the time of ASCT. Here, preliminary data on 187 pts are presented. For pts receiving more than one ASCT (n=69), only data on the first ASCT were included in the analysis. Pts treated with MEL140 and MEL100 were pooled (MELRed group). Results Of 187 ASCTs, 163 were performed as first-line and 24 as salvage therapies. Median follow up of the entire population was 77 months (range 3-172). Induction treatment included at least 1 novel agent (immunomodulatory drugs, IMiDs or proteasome inhibitors, PI) in 119 pts, whilst 68 pts received conventional chemotherapy. Median number of induction cycles before ASCT was 3 (range 1-10). Prior to ASCT 31 pts (17%) had achieved at least a very good partial remission (VGPR). MEL200 was used in 112 (60%) and MELRed in 75 pts (40%, 72 MEL140 and 3 MEL100). There was no difference in the two groups in the number of transplant performed as first line or as salvage therapy (p=0.54), as well as in the rate of pts achieving at least a VGPR before ASCT (17% vs. 16%, for MEL200 and MELRed respectively, p=0.84). More pts treated with MEL200 received induction treatment containing novel agents (70% vs. 55% for MEL200 and MELRed respectively, p=0.037). High quality responses (≥VGPR) after ASCT were higher in the MEL200 group: 89% of pts treated with MEL200 vs. 73% of those receiving MELRed, p=0.005. The main reasons for MEL dose reduction were older age (40%) and renal insufficiency (29%). Median age (range) and creatinine values (range) were 55 (35-68) vs. 63 (47-70) years (p<0.001) and 73 (51-186) vs. 90.5 (51-1022) μmol/l (p<0.001) for MEL200 and MELRed, respectively. More pts in the MELRed group had a Charlson Comorbidity Index (CCI) >2 (83% vs. 99% for MEL200 and MELRed respectively, p=0.001). Toxicities and duration of hospitalization of the two groups are depicted in Table 1. The higher response rate seen in pts treated with MEL200 translated in a longer median PFS (43 vs. 27 months for MEL200 and MELRed respectively, p=0.023) and OS (66% vs. 51% at 5 years for MEL200 and MELRed respectively, p=0.046). Multivariate analysis included CCI >2, response before and after ASCT ≥VGPR, disease stage at ASCT, age >65 years, treatment with new drugs, glomerular filtration rate ≥60 ml/min at the time of ASCT and treatment with MEL200. Disease stage (HR 0.57, 95% CI 0.331-0.978, p=0.041) and MEL200 (HR 0.49, 95% CI 0.295-0.802, p=0.005) were associated with an improved PFS, whilst none of the above mentioned variables had an impact on OS. Conclusion In comparison with MELRed, MEL200 provides favorable responses and improves PFS and OS with only moderate increase of toxicity in this retrospective pts cohort. At least in pts treated with standard-induction therapy, MEL200 should be considered the standard conditioning regimen for ASCT eligible MM pts. Disclosures Brioli: Janssen: Honoraria; Celgene: Honoraria, Other: Travel support, Research Funding. Mügge:Amgen: Honoraria; Novartis: Honoraria; Janssen: Honoraria; Bristol Myers Squibb: Honoraria; Celgene: Honoraria, Research Funding. Scholl:Abbivie: Other: Travel support; Jazz Pharma: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Novartis: Other: Travel support; Deutsche Krebshilfe: Research Funding; Alexion: Other: Travel support; MDS: Other: Travel support; Carreras Foundation: Research Funding. Hilgendorf:Novartis: Other: Travel support, Research Funding; Medac: Other: Travel support, Research Funding. Sayer:RIEMSER Pharma GmbH: Honoraria. Ernst:Novartis: Research Funding. Hochhaus:Incyte: Research Funding; Novartis: Research Funding; Takeda: Research Funding; Pfizer: Research Funding; Bristol-Myers Squibb: Research Funding. von Lilienfeld-Toal:Takeda: Honoraria, Other: Travel support, Research Funding; Novartis: Honoraria, Other: Travel support, Research Funding; Celgene: Honoraria, Other: Travel support, Research Funding; Janssen: Honoraria, Other: Travel support, Research Funding.

scholarly journals Characteristics of a Comprehensive, Continuously Updated Longitudinal Database for Multiple Myeloma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4969-4969
Author(s):  
C. Anthony Blau ◽  
Grace Nam ◽  
Leena Chhun ◽  
Cheng Zheng ◽  
Jayne Piboonvaranggoon ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Disease Control ◽  
Board Of Directors ◽  
Real World ◽  
Research Funding ◽  
Disease Stage ◽  
Publicly Traded ◽  
Advisory Committees ◽  
Multi Agent

Abstract Introduction: Despite the availability of many effective agents, multiple myeloma is characterized by repeated cycles of treatment response and relapse, and remains incurable in almost all patients. Efforts to optimize treatment are complicated by variation in disease biology and by the combinatorial complexity inherent in assembling, sequencing and administering multi-agent regimens. Determining which strategies provide maximal therapeutic benefit requires deploying a variety of multi-agent regimens in a range of settings and assessing long-term outcomes; information that cannot be readily discerned from clinical trials. Here we present results from a real-world database that comprehensively tracks all treatments and responses in patients with multiple myeloma. Methods: Since March 2017, All4Cure has hosted an online platform for patients with multiple myeloma, clinicians and researchers that has been initially focused in the Pacific Northwest. Medical records from consenting patients are collected and information regarding all treatments and responses graphically displayed on their de-identified dashboards. A discussion panel allows for asynchronous communication between members of All4Cure's community of patients, clinicians and researchers (currently numbering over 1600 participants). There is no charge to patients who participate in All4Cure, and clinicians and researchers are neither charged nor paid for their participation. A summarized real-world database describes the lines of therapy that each patient has received, treatment start and stop dates, and responses in accordance with International Myeloma Working Group (IMWG) criteria. Results: The overall profile of patients with multiple myeloma enrolled in All4Cure (N=555) was benchmarked against myeloma patients from the National Program of Cancer Registries (NPCR) (diagnosis year 2017; N=25,895). Patients in all 50 States and D.C. were included in the comparison, and those with monoclonal gammopathy of undetermined significance (MGUS) were not considered. Myeloma patients enrolled in All4Cure are younger at diagnosis or start of treatment (median 61 versus between 65 and 69), more likely to be white (90.3% versus 73.5%), and more likely to reside in Washington State (41.2% versus 2%) compared to the NPCR cohort, reflecting participation influenced by geographic location as described above. After enrollment, All4Cure patients are followed longitudinally throughout the entirety of their disease course, with fewer than 2% having been lost to follow up. To gain insights uniquely available from the All4Cure database and to inform the future direction for our research, we focus our exploratory data analysis on the All4Cure cohort of patients who started treatment in June 2015 or later (N=299). Despite the relatively recent start of the All4Cure database, this timeframe allows up to 6 years of observation following the start of treatment, since the survival rates for the first 1-2 years of treatment are generally very high. Consistent with prior knowledge, increasing age and disease stage are associated with increased morality, as are high-risk cytogenetics such as 17p-, t(4:14) and t(14;16). We further explored the potential impact of early lines of therapy on long-term disease control. While the current literature is mixed on the merits of aggressive treatments in early lines of therapy in terms of overall survival, insights from our data suggest that more aggressive front-line therapies (such as SCT) are associated with improved disease control over time, although this is evolving with the impact of novel therapies and in particular the use of triplet and now quadruplet induction regimens and adapting treatment to achieve measurable residual disease (MRD) negativity. Conclusions: Even with the current limitations regarding the size and representativeness of All4Cure's database, these preliminary results support the validity of this approach for gaining insight into the treatments and outcomes of patients with multiple myeloma in real-world settings. Disclosures Blau: Oncopeptides: Other: Oncopeptides is an All4Cure customer. Blau: All4Cure: Current equity holder in publicly-traded company. Richter: Tisch Cancer Institute: Icahn School of Medicine at Mount Sinai: Current Employment; Janssen, Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Adaptive biotechnologies: Speakers Bureau; BMS, Karyopharm, Antengene: Membership on an entity's Board of Directors or advisory committees. Bensinger: BMS, Janssen, Poseida, Regeneron, Trillium: Research Funding; Amgen, BMS, Janssen, Sanofi: Speakers Bureau. Richardson: Secura Bio: Consultancy; Protocol Intelligence: Consultancy; Sanofi: Consultancy; Jazz Pharmaceuticals: Consultancy, Research Funding; AstraZeneca: Consultancy; Oncopeptides: Consultancy, Research Funding; AbbVie: Consultancy; GlaxoSmithKline: Consultancy; Regeneron: Consultancy; Janssen: Consultancy; Karyopharm: Consultancy, Research Funding; Celgene/BMS: Consultancy, Research Funding; Takeda: Consultancy, Research Funding. Anderson: Sanofi-Aventis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Millenium-Takeda: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Scientific Founder of Oncopep and C4 Therapeutics: Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Mana Therapeutics: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Frontline Brentuximab Vedotin As Monotherapy or in Combination for Older Hodgkin Lymphoma Patients

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 18-19
Author(s):  
Christopher A. Yasenchak ◽  
Rodolfo Bordoni ◽  
Dipti Patel-Donnelly ◽  
Timothy Larson ◽  
Jerome Goldschmidt ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Hodgkin Lymphoma ◽  
Older Patients ◽  
Research Funding ◽  
Brentuximab Vedotin ◽  
Disease Stage ◽  
Publicly Traded ◽  
Advisory Committees ◽  
Meaningful Improvement ◽  
Part C

Introduction: Older patients with classical Hodgkin lymphoma (cHL) have poor outcomes relative to younger patients, often due to comorbidities and toxicities related to standard first-line (1L) chemotherapy (5-yr PFS: 30%-45% vs 75%-80%) (Evens 2008; Proctor 2009). Brentuximab vedotin (BV), a CD30-directed antibody-drug conjugate, has robust activity in patients refractory to several lines of chemotherapy. Methods: This phase 2, open-label study, SGN35-015 (NCT01716806), evaluated efficacy and tolerability of BV alone or combined with single-agents in treatment-naive cHL patients ≥60 yr. The full-analysis set (FAS) includes all patients who received BV (1.8 mg/kg IV). Patients in Part A received BV monotherapy on Day 1 of every 3-week cycle (n=26); Part B: BV+dacarbazine (DTIC; 375 mg/m2; n=19); Part C: BV+bendamustine (benda; 70 mg/m2; n=20); and Part D: BV+nivolumab (nivo; 3 mg/kg; n=20). The efficacy evaluable (EE) set includes FAS who had at least 1 post-baseline response assessment (n=25, 19, 17, 19). Results: Demographic characteristics were generally similar: median age 78, 69, 75, and 72 yr in Parts A, B, C, and D, respectively, and 62% of patients (range 45%-70%) reported impaired physical functioning at baseline. Most patients had disease stage III/IV (62%, 68%, 75%, 80%), were ECOG 0/1 (77%, 74%, 80%, 95%), and male (54%, 68%, 50%, 75%). Median time from diagnosis was 1.2 to 1.5 mo (FAS; 10 Jan 2020 data cutoff). ORR were high (92% [95% CI: 74%, 99%], 100% [95% CI: 82.4%, 100%], 100% [95% CI: 80.5%, 100%], 95% [95% CI: 74%, 99.9%]) at a median follow-up of 59.4, 58.6, 51.3, and 19.4 mo in the EE data set. Median PFS in the EE set was 10.5 mo (95% CI: 5.6, 77.5) with monotherapy and 46.8 mo (95% CI: 11.0, 68.7), 40.3 mo (95% CI: 4.8, NR), and not reached (95% CI: 9.4, NR) in the combination parts. Median OS in the FAS set was 77.5 mo (95% CI: 40.1, NR) with monotherapy; 64.0 (95% CI: 53.4, NR), 46.9 (95% CI: 6.8, NR), and not reached (95% CI: NR, NR) in the combination parts. Treatment-related adverse event (AE) ≥ Grade 3 occurred in 50%, 37%, 70%, and 60% of patients; peripheral neuropathy (PN) was most common (35%, 26%, 20%, 35%). Treatment-related serious AEs occurred in 12%, 11%, 40%, and 5% of patients. Part C enrollment (BV+benda) closed early due to multiple acute toxicities. There were no treatment-related deaths in any part of the study. The median treatment cycles per patient were 8.0, 12.0, 5.0, and 14.5. Treatment discontinuation due to related AEs occurred in 42%, 42%, 40%, and 30% of patients, most commonly due to PN (38%, 37%, 30%, 20%). Conclusions: Older patients with cHL and multiple comorbidities have very high response rates and a clinically meaningful improvement in PFS with BV as monotherapy or combined with other single agents and improved tolerability versus combination chemotherapy. Median overall survival exceeded 6 yrs with BV monotherapy. BV+nivo or BV+DTIC appeared to be the most reasonable combination treatment options in this study. Disclosures Yasenchak: BeiGene: Speakers Bureau; Seattle Genetics: Honoraria, Research Funding; Takeda: Honoraria. Bordoni:Takeda: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Guardant Health: Honoraria, Speakers Bureau; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, Patents & Royalties; Northside Hospital Cancer Institute: Other: Uncompensated relationship; Practice Point Communications: Other: Uncompensated relationship; Foundation Medicine: Membership on an entity's Board of Directors or advisory committees; Genentech: Honoraria, Speakers Bureau; G1 Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Patel-Donnelly:Gilead: Research Funding; Boston Biomedical: Research Funding; Roche: Research Funding; LAM Therapeutics: Research Funding. Goldschmidt:Amgen: Consultancy; Bristol-Myers Squibb: Speakers Bureau; Blue Ridge Cancer Care: Current Employment. Boccia:Rigel: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Incyte: Consultancy, Honoraria, Research Funding, Speakers Bureau; Genentech: Consultancy, Honoraria, Research Funding, Speakers Bureau; Daiichi Sankyo: Consultancy, Honoraria, Research Funding, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau. Cline:Pfizer: Honoraria; Reflexion Medical: Consultancy, Other: Travel expenses; Texas Oncology: Current Employment. Sacchi:Bristol-Myers Squibb Company: Current Employment. Forero-Torres:Seattle Genetics, Inc.: Current Employment, Current equity holder in publicly-traded company. Sims:Seattle Genetics, Inc.: Current Employment, Current equity holder in publicly-traded company, Other: Travel expenses. Liu:Seattle Genetics, Inc.: Current Employment, Current equity holder in publicly-traded company. Friedberg:Roche: Other: Travel expenses; Portola Pharmaceuticals: Consultancy; Bayer: Consultancy; Astellas: Consultancy; Acerta Pharma - A member of the AstraZeneca Group, Bayer HealthCare Pharmaceuticals.: Other; Kite Pharmaceuticals: Research Funding; Seattle Genetics: Research Funding.

scholarly journals Real-Word Clinical Management of Patients Treated with Idelalisib in France: A Study of 529 Cases of Chronic Lymphocytic Leukemia (CLL) and Follicular Lymphoma (FL)

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2302-2302
Author(s):  
Anne-Sophie Michallet ◽  
Emmanuel Gyan ◽  
Pierre Feugier ◽  
Ana Nunes ◽  
Tarek Abdelhadi ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Board Of Directors ◽  
Treatment Duration ◽  
Research Funding ◽  
Disease Stage ◽  
Pneumocystis Jirovecii Pneumonia ◽  
Real Word ◽  
Duration Of Treatment ◽  
Advisory Committees ◽  
Practice Survey

Abstract Introduction: Idelalisib (IDELA), the first PI3K delta inhibitor, is indicated in Europe in combination with rituximab (R) or ofatumumab for the treatment of adult patients (pts) with CLL and as monotherapy for the treatment of adult pts with refractory FL. IDELA provides an important therapeutic option for the management of CLL and FL, but there are few real word data on its effectiveness and safety. The objective of this study was to describe the management of IDELA therapy in a real word setting in France for patients with CLL or FL. Methods: This multi-center retrospective clinical practice survey started in February, 2017 and ended in July, 2017. During this period, 52 physicians agreed to complete a questionnaire collecting data for each pt they have treated with IDELA according to the marketing authorization label: demographic, clinical and biological pt characteristics at the time of IDELA initiation; pt follow-up modalities including nurse and pharmacist consultations; conditions of IDELA use; duration of treatment; reasons for discontinuation; and treatment administered before and after IDELA discontinuation. Analyses were conducted separately in CLL and FL groups and data are presented descriptively. Results: The 52 participating physicians were geographically well distributed and were mostly located at regional hospitals (44%) or university hospitals (38%). Data on 529 pts were collected, including 384 CLL pts (20.1% 1L, 33.9% 2L, 46% 3L+) and 145 FL pts (60.7% 3L, 26.9% 4L, 12.4% 5L+), of whom 61% and 63% respectively were still on treatment at the time of the survey. For CLL/FL respectively, median age was 69 y/68 y, 27.6%/24.8% were aged > 75 y, 76.7%/72.0% were ECOG 0-1, median number of comorbidities was 1.0 for both CLL and FL with hypertension as the most common and median prior therapies was 2 in both groups. For CLL pts, 65.1% had disease stage Binet C and most had poor prognostic markers (14.6% del(11q), 44.0% del(17p) and 19.7% TP53 mutation). IDELA was initiated, at 150 mg BID in 90.6%/93.8% of CLL/FL pts respectively. Median duration of treatment was 24.0 months for overall CLL and not reached in del(17p)/TP53m sub-group and in FL group. Independent predictors of longer treatment duration were ECOG ≤ 1, prophylaxis against Pneumocystis jirovecii Pneumonia (PJP) or cytomegalovirus (CMV) infections and consultation with a nurse at initiation of treatment in the CLL group and ECOG score ≤ 1 in the FL group (Table 1, 2). Most of CLL/FL pts respectively had a nurse consultation at the start of IDELA (68.0%/56.6%) and prophylaxis for PJP or CMV (93.0%/77.0%). Sixty nine percent of pts in each group were tested for CMV before starting IDELA. In CLL/FL groups respectively, 61 pts (15.9%)/22 pts (15.2%) had at least one IDELA dose interruption. Diarrhea was the main reason for interruption (G1-2: 28%/11%, G3-4: 21%/21%) followed by neutropenia (30%/18%), pneumonia (11%/25%, non-infectious: 1%/7%) and ALT/AST elevation (6%/14%). IDELA was permanently discontinued in 152 CLL pts/54 FL pts respectively, mainly for disease progression (34%/41%), diarrhea G3-4 (16%/6%), diarrhea G1-2 (4%/2%), remission or good response (9%/19%), pneumonia (9%/13%, non-infectious: 3%/7%), neutropenia and ALT/AST elevation (5%/2% each). Of 151 CLL pts/54 FL pts who permanently discontinued IDELA, 83 (55%)/34 (63%) received subsequent treatment, mainly ibrutinib monotherapy (70%) in the CLL group and chemotherapy combined with anti-CD20 (63%) in the FL group. Conclusion: This large clinical practice survey provides useful information about the management of IDELA treatment across France and permits factors predictive of treatment duration to be identified. Most FL pts had advanced disease and most CLL pts had genetic markers of poor prognosis. Safety was in accordance with the known safety profile of IDELA. PJP prophylaxis contributed to longer duration of treatment in CLL and should be prescribed to all pts receiving IDELA. Consultation with a nurse before and during treatment helps manage CLL and FL pts treated with IDELA and can prolong duration of treatment. Disclosures Feugier: Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Nunes:Gilead Sciences: Employment. Abdelhadi:Gilead Sciences: Employment. Ysebaert:Roche: Consultancy, Research Funding; Gilead Sciences, Inc.: Consultancy, Research Funding; Janssen: Consultancy, Research Funding.

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