scholarly journals Generalizability of Landmark Clinical Trials in Diffuse Large B Cell Lymphoma to Real-World Patients: A Single-Centre Retrospective Cohort Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 17-18
Author(s):  
Marta Davidson ◽  
Alexandra Rice ◽  
Douglas A. Stewart ◽  
Carolyn Owen
Keyword(s):  
Clinical Trials ◽  
B Cell ◽  
Real World ◽  
Cell Lymphoma ◽  
Performance Status ◽  
Poor Performance ◽  
B Cell Lymphoma ◽  
Poor Performance Status ◽  
Novel Therapies ◽  
Alberta Cancer Registry

Background: Clinical trials are the gold standard by which therapies in oncology are evaluated and ultimately form the bases for approval of novel therapies. Stringent eligibility criteria limit the participation of many "real-world" patients and thus undermine the generalizability of trial results. Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of Non-Hodgkin lymphoma (NHL) and is curable in the majority of patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). The addition of rituximab to CHOP is the only clear advancement in DLBCL therapy in the last 20 years. Though a large minority of patients are not cured by R-CHOP, several subsequent novel therapies have failed to demonstrate benefit in Phase 3 clinical trials. We hypothesized that real world patient populations differ from clinical trial populations with trial eligibility excluding the poor-outcome patients who might benefit most from novel therapy. Methods: We performed a retrospective chart review of all patients 18 years of age or older who were registered within the Alberta Cancer Registry with a new diagnosis of pathology-confirmed DLBCL, between January 1, 2010 and December 31, 2011. Clinical characteristics were reviewed to assess patient eligibility to participate in 3 landmark clinical trials for DLBCL on the basis of inclusion and exclusion criteria defined by each study. The trials included Pfreundschuh, M. et al. (2006) and Coiffier, B. et al. (2002), which were assessed together as representing the landmark studies for rituximab added to CHOP, and the GOYA trial (2017) which evaluated obinutuzumab-CHOP vs R-CHOP. Categorical variables are presented as frequencies and percentages. Univariate probabilities of overall-survival were calculated by Kaplan-Meier method. Results: We identified 480 patients with a diagnosis of DLBCL within the Alberta Cancer Registry. A total of 390 patients were eligible for our study with 20 patients excluded for CNS lymphoma, 29 for unclassifiable B-cell lymphoma, 2 patients who died at the time of diagnosis, and 25 patients with previously treated indolent lymphoma. In addition, 14 patients were excluded for insufficient clinical data. Table 1 demonstrates the clinical characteristics of the population. Out of 390 patients, only 130 (33%) patients met inclusion for the rituximab studies and 134 (34%) for the GOYA study. Table 2 demonstrates the most common criteria leading to trial exclusion, including poor performance status, limited stage disease, inappropriate IPI, transformed lymphoma, history of second primary malignancy, and viral infections. Trial ineligible patients had significantly inferior overall survival compared to trial eligible patients (Figure1). Conclusions: The majority of real-world DLBCL patients are excluded from clinical trials and have inferior outcomes compared to trial eligible patients. The selection of patients with more favourable outcomes for clinical trials may contribute to failure to demonstrate a benefit of novel therapies. Broadening inclusion criteria to include patients with transformed disease and poor performance status could aid in improving the generalisability of DLBCL clinical trials. Disclosures Stewart: Gilead: Honoraria; Roche: Honoraria; Celgene: Honoraria; Amgen: Honoraria; Abbvie: Honoraria; Janssen: Honoraria; Teva: Honoraria; Sandoz: Honoraria; AstraZeneca: Honoraria; Novartis: Honoraria. Owen:AbbVie, F. Hoffmann-La Roche, Janssen, Astrazeneca, Merck, Servier, Novartis, Teva: Honoraria.

scholarly journals Poor Prognosis of Diffuse Large B-Cell Lymphoma with Hepatitis C Infection

2021 ◽  
Vol 11 (9) ◽  
pp. 844
Author(s):  
Yu-Fen Tsai ◽  
Yi-Chang Liu ◽  
Ching-I Yang ◽  
Tzer-Ming Chuang ◽  
Ya-Lun Ke ◽  
...  
Keyword(s):  
Hepatitis C ◽  
B Cell ◽  
Cell Lymphoma ◽  
Performance Status ◽  
Poor Performance ◽  
B Cell Lymphoma ◽  
Liver Involvement ◽  
Poor Performance Status ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Background: Hepatitis C virus (HCV) in diffuse large B-cell lymphoma (DLBCL) is associated with a higher prevalence and distinctive clinical characteristics and outcomes. Methods: A retrospective analysis of adult DLBCL patients from 2011 to 2015 was studied. Results: A total of 206 adult DLBCL were enrolled with 22 (10.7%) HCV-positive patients. Compared to HCV-negative patients, the HCV-positive group had a poor performance status (p = 0.011), lower platelet count (p = 0.029), and higher spleen and liver involvement incidences (liver involvement, p = 0.027, spleen involvement, p = 0.026), and they received fewer cycles of chemotherapy significantly due to morbidity and mortality (p = 0.048). Overall survival was shorter in HCV-positive DLBCL (25.3 months in HCV-positive vs. not reached (NR), p = 0.049). With multivariate analysis, poor performance status (p < 0.001), advanced stage (p < 0.001), less chemotherapy cycles (p < 0.001), and the presence of liver toxicity (p = 0.001) contributed to poor OS in DLBCL. Among HCV-positive DLBCL, the severity of liver fibrosis was the main risk factor related to death. Conclusion: Inferior survival of HCV-positive DLBCL was observed and associated with poor performance status, higher numbers of complications, and intolerance of treatment, leading to fewer therapy. Therefore, anti-HCV therapy, such as direct-acting antiviral agents, might benefit these patients in the future.

Definition, Diagnosis, and Management of Intravascular Large B-Cell Lymphoma: Proposals and Perspectives From an International Consensus Meeting

2007 ◽  
Vol 25 (21) ◽  
pp. 3168-3173 ◽  
Author(s):  
Maurilio Ponzoni ◽  
Andrés J.M. Ferreri ◽  
Elías Campo ◽  
Fabio Facchetti ◽  
Luca Mazzucchelli ◽  
...  
Keyword(s):  
B Cell ◽  
Clinical Features ◽  
Cell Lymphoma ◽  
Performance Status ◽  
Poor Performance ◽  
B Cell Lymphoma ◽  
Poor Performance Status ◽  
International Consensus ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Intravascular large B-cell lymphoma (IVLBCL) is a rare form of diffuse LBCL characterized by preferential intravascular growth of malignant lymphocytes, aggressive behavior, and an often fatal course. IVLBCL usually affects elderly patients with poor performance status, elevated lactic dehydrogenase serum levels, anemia, and B symptoms. It displays some differences in clinical presentation among diverse geographical areas, mostly between patients diagnosed in Western countries and Japan. In addition, data from the literature suggest that pathologic diagnostic criteria as well as clinical features of this disease may be broader than described in current classification scheme(s). Under the sponsorship of the International Extranodal Lymphoma Study Group, clinicians and pathologists with interest in IVLBCL, coming from Western and Eastern countries, joined to reach a consensus on defining features as well as to focus on the most urgent unresolved issues in IVLBCL. To this end, a representative group of IVLBCL patients coming from both the aforementioned geographical areas were collectively analyzed. Additional features of IVLBCL were proposed both under clinical and pathologic stand points. At the meeting, it emerged that IVLBCL may have additional histopathologic/cytologic definition criteria with respect to those currently recommended, some clinical features are not randomly distributed worldwide, recent therapeutic approaches, such as anti-CD20–containing regimens, may improve outcome, and kidney, spleen, and liver involvement may show peculiar histopathologic features. Finally, a provisional practical diagnostic approach to hemophagocytosis-associated patients and a proposal for the most useful criteria in the settings of differential diagnosis are included.

scholarly journals Perceptions of Community Hematologists/Oncologists on Barriers to Chimeric Antigen Receptor T-Cell Therapy for the Treatment of Diffuse Large B-Cell Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2198-2198
Author(s):  
Ajeet Gajra ◽  
Richard Sweat ◽  
Yolaine Jeune-Smith ◽  
Jonathan K. Kish ◽  
Bruce A Feinberg
Keyword(s):  
Clinical Trials ◽  
B Cell ◽  
Annual Meeting ◽  
Real World ◽  
Randomized Clinical Trials ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
The United States ◽  
Large B Cell Lymphoma ◽  
Car T

Introduction The ASH Annual Meeting is a venue for presentation of outcomes data from key clinical trials in hematologic malignancies and novel drug classes used to treat them. The approval of two CAR-T therapies, axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tis-cel), in the treatment of large B-cell lymphoma (LBCL), including diffuse LBCL (DLBCL), has ushered in a new class of drugs, i.e. cellular therapy. At ASH 2018, Nastoupil et al. presented data from a retrospective analysis of the characteristics and outcomes of patients with relapsed/refractory LBCL, including DLBCL, treated with commercially available axi-cel CAR-T therapy at academic centers in the United States (Nastoupil LJ, et al. Blood. 2018;132[Suppl 1]:91). The authors found that early outcomes of real-world patients receiving axi-cel therapy were comparable to those observed in the clinical trial population, despite >40% of these patients failing to meet the clinical trial eligibility criteria. At a live meeting in February 2019, we sought the perceptions of community hematologists and oncologists (H/O) regarding their use of, referrals for and barriers to CAR-T therapy as well their perception of the value of the real-world evidence (RWE) presented. Methods A live meeting in February 2019 convened H/O with geographic representation from across the United States. The participants were shown data from selected oral and/or poster presentations from the 2018 ASH Annual Meeting and responded to questions regarding their perceptions of the data and its potential impact on current practice. Participants submitted their demographic responses via a web-based survey prior to the meeting and data impression responses via an audience response system at the live meeting. Results Among the 59 H/O who participated in this live market research program on February 22-23, 2019, 61% identified their primary specialty as hematology/oncology and 34% medical oncology. Only 27% of H/O had attended the 60th ASH Annual Meeting in December 2018. The participants were mostly community-based physicians, 50% in private community and 45% in community practices owned by a hospital or academic center. One-third have been in practice for over 20 years, one-third for 11-20 years and one-third for 10 or fewer years. This group sees an average of 20+ patients per day and reported B-cell non-Hodgkin lymphoma as one of the three most common hematologic malignancy they managed. 28% of H/O indicated that they have referred one patient and 24% have referred 2-5 patients for CAR-T therapy since the first approval on August 30, 2017. Of those H/O who had referred patients for CAR-T therapy, 45% indicated that none of their patients had yet received the infusion. The top two barriers to prescribing/recommending CAR-T therapy, as reported by the H/O, were the cumbersome logistics of administering therapy and following patients (52%), and the cost of the therapy (46%). Other concerns included high toxicity (24%) and lack of long-term survival data (19%), but not lack of knowledge of CAR-T therapy (2%). Furthermore, 87% of H/O agreed with the assertion that due to the limitations of randomized clinical trials, RWE is necessary to inform clinical practice. After review of the information presented on the real-world use of axi-cel, 73% of H/O indicated that this information is likely to cause them to recommend CAR-T therapy for more of their patients with DLBCL. Conclusions There is significant interest in adopting and using CAR-T therapies in LBCL amongst community H/O. This group does not perceive itself as lacking in knowledge regarding CAR-T therapy. The significant barriers of logistics and cost are potential deterrents to appropriate use. These results can inform stakeholders (manufacturers, payers, hospitals and practices) regarding the need to improve processes and develop payment models to address cost in order to facilitate access of these agents to the appropriate patients. RWE is viewed favorably by the vast majority of community H/O to inform clinical practice, due to the limitations of randomized clinical trials. Disclosures Gajra: Cardinal Health: Employment. Sweat:Cardinal Health: Employment. Jeune-Smith:Cardinal Health: Employment. Kish:Cardinal Health: Employment. Feinberg:Cardinal Health: Employment.

Elderly Very Poor Performance Status Patients with Aggressive B Cell Lymphomas Can Gain Long Term Remissions with Intensive Chemotherapy with Encouraging Response Rates and Overall Survival (OS).

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2794-2794
Author(s):  
Stella J Bowcock ◽  
Vincenzo Fontana ◽  
Yvonne Noble ◽  
Susan Ward ◽  
Keith Winyard ◽  
...  
Keyword(s):  
B Cell ◽  
Conflicts Of Interest ◽  
Performance Status ◽  
Poor Performance ◽  
B Cell Lymphoma ◽  
Late Relapse ◽  
Poor Performance Status ◽  
Intensive Chemotherapy ◽  
B Cell Lymphomas ◽  
Curative Intent

Abstract Abstract 2794 Introduction Patients (pts) of older age, poor performance status (PS) and advanced stage with aggressive B cell lymphomas are regarded as poor prognosis and may receive no treatment, or palliative rather than curative chemotherapy. Studies suggest these pts may be undertreated and poor outcome may be partly related to undertreatment. Our unit has had a policy of offering treatment with curative intent to all pts presenting with aggressive B cell lymphomas, whatever their age or PS providing comorbidities allow. We reviewed the outcome of this policy. Methods All pts age≥70 years with diffuse large B cell lymphoma (DLBCL) or Burkitts lymphoma (BL) between 2000–2010 incl. were found from histology, chemotherapy and registry records. Poor PS pts were selected by including all who were inpatients during their 1st chemotherapy cycle, or if untreated, at diagnosis. If ECOG PS had not been prospectively recorded, ≥2 staff (from the 6 who were present throughout the 10 years) independently attributed status from memory and hospital notes. Only confirmed bedbound pts were designated PS4. Percentage chemotherapy doses delivered were calculated against the projected full dose and categorised into ≥85% Full, 60–85% RD, 30–60% HD. Pts receiving CHOP±R or CODOX-M/IVAC were called intensive (Int) and pts receiving low dose regimens called non-intensive (NI). Results 61 pts were found and 37 were inpatients. Of the 37 inpatients, 30 received chemotherapy, 29 for DLBCL and 1 for BL. Of the 30 treated pts (table 1) where parameters were assessable, LDH raised 92%, R-IPI ≥3 97%, PS 3/4 in 93%, stage3/4 86%, albumin <35g/l 70%. Of the 30 patients treated with chemotherapy, 18 achieved a CR with a median OS of 39 months(m) (range 8–123). There were 23 Int pts (9 were PS4, 7 of these being moribund), and 16 achieved CR median OS 48 m (range 12–99), 6 of them being PS4 and 4 were moribund. All pts achieving CR remained so except 1 late relapse (96m). Comorbidities were supported but did not influence treatment decisions except poor ejection fraction or dementia. (7 patients received no chemotherapy; declined ×3, cancer ×1, dementia ×1, not referred ×2) Discussion Our data show that very poor PS elderly pts can achieve CR (70%) with good OS with current intensive chemotherapy (CHOP±R, CODOX-M/IVAC±R). Further discussion refers to these pts (Int). CRs not only occurred in the PS2/3 pts, but also in 6/9 PS4 pts. The survivors could not be predicted and included 4 moribund pts. Toxicities were acceptable. Three of 4 moribund pts who survived received HD chemotherapy which was staggered due to emergency presentation. The 2nd cycle was given as soon as possible if improvement occurred (all responders did) with escalation of chemotherapy doses. This aggressive chemotherapeutic approach may have contributed to the good response rate. Our data show that putative toxicity is not a barrier to treatment with judicious dose reduction in the 1st cycle. Retrospective PS attribution was a weakness of the study. But objective parameters eg LDH, IPI, albumin and chemotherapy dose delivered concurred with the scores supporting their validity. PS4 criteria were objective. These data are important because they represent pts mostly excluded from trials. Recent data suggest that comorbidities may not influence survival. Our data support this. We suggest that elderly very poor PS pts can tolerate curative chemotherapy with encouraging remission rates and OS. Previous poor results may be due partly to undertreatment and most pts should be offered proper curative chemotherapy. A positive medical team attitude may be important. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Neutrophil-Lymphocyte Ratio Is a Prognostic Marker in Patients with EBV-Positive Diffuse Large B-Cell Lymphoma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5047-5047
Author(s):  
Brady E Beltran ◽  
Jose M Malaga ◽  
Julio C Chavez ◽  
Eduardo M. Sotomayor ◽  
Jorge J Castillo
Keyword(s):  
B Cell ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
Performance Status ◽  
Poor Performance ◽  
B Cell Lymphoma ◽  
Advanced Stage ◽  
Lymphocyte Ratio ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Introduction: Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) is a rare hematologic malignancy with a poor prognosis when treated with current therapies. Clinical factors have been developed to prognosticate survival in EBV-positive DLBCL patients; however, more refined, easy to use and reliable prognostic tools are needed. The neutrophil to lymphocyte ratio (NLR) has been reported prognostic in patients with DLBCL (Troppan et al. BJC 2014). We have investigated the prognostic value of the NLR in the overall survival (OS) of patients with untreated EBV-positive DLBCL. Methods: We included patients with a pathological diagnosis of EBV-positive DLBCL who were diagnosed and treated at our institution between 2001-2014. We excluded cases with primary cutaneous CNS involvement, and patients with >50% incomplete data. IRB approval was obtained prior to research. Pathological samples were reviewed by hematopathologists to confirm the diagnosis. Pertinent clinicopathological data such as age, sex, performance status, LDH levels, stage, extranodal sites of disease, absolute neutrophil and lymphocyte counts were collected through chart review, and are presented using descriptive statistics. The NLR was calculated by dividing the absolute neutrophil by the lymphocyte count, and dichotomized in NLR>=5 and NLR<5. Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Univariate Cox models were fitted to evaluate hazard ratios (HR) for OS. Results: A total of 46 patients were included in our analysis. The median age was 73 years (range 25-95 years) with male predominance (70%). Poor performance status (ECOG >1) was seen in 25 (58%), elevated LDH levels in 19 (46%), 1+ extranodal site in 24 (57%), and advanced stage (stage 3 and 4) in 23 (53%) of patients. Based on the NLR, 13 patients (39%) had NLR>=5. Patients with NLR >=5 were more likely to present with poor performance (ECOG >1; 85% vs. 15%; p=0.04), elevated LDH levels (69% vs. 31%; p=0.04), advanced stage (III and IV, 69% vs. 31%, p=0.05), and IPI score 3-5 (77% vs.23%; p=0.02). There were no differences in age, sex and number of extranodal sites. NLR>=5 was associated with a worse OS (HR 2.67, 95% CI 1.01-7.01; p=0.047). Conclusion: The NLR appears as a novel and easy to use prognostic factor for OS in patients with untreated EBV-positive DLBCL. Our findings support the need for validation of the NLR in larger retrospective or prospective studies in patients with EBV-positive DLBCL. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

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