scholarly journals Exploring the Impact of Diffuse Large B-Cell Lymphoma (International Prognostic Index [IPI] 2-5) on Clinical and Patient-Relevant Outcomes in the Context of a Clinical Trial

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3577-3577
Author(s):  
Aino Launonen ◽  
Rodrigo Ho ◽  
Andrea Knapp ◽  
Irene Canales Ruiz ◽  
Leonardo Simonella ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Utility Score ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Late Relapse ◽  
Early Relapse ◽  
Large B Cell Lymphoma ◽  
Treatment Start ◽  
Anxiety Depression ◽  
Large B Cell

Abstract Background: Most patients (pts) with diffuse large B-cell lymphoma (DLBCL) receiving first-line (1L) rituximab plus CHOP (R-CHOP) have similar mortality to the general population (gen popn) if they are progression-free at 24 months (PFS24; Maurer et al. Ann Oncol 2018). Characterization of quality of life (QoL) and clinical outcomes may enable more patient-relevant treatment decisions. Using GOYA trial data (NCT01287741) comparing obinutuzumab (G) + CHOP (G-CHOP) with R-CHOP, we present an exploratory analysis of 1L DLBCL pts with IPI 2-5 and assess overall survival (OS) and QoL relative to the gen popn. GOYA was not included in the previous PFS24 analysis by Maurer et al. Methods: We used data from both GOYA treatment arms to identify pts with IPI 2-5 DLBCL (n=1132 pts, intent-to-treat popn). Post-progression survival (PPS) in DLBCL is independent of prior treatment (Coiffier et al. Blood 2010) and as PFS was similar between treatment arms in GOYA, we assumed similar mortality after PFS24. Clinical outcomes were PFS24 (progression-free ≥24 months [m] from treatment start); early relapse (disease progression [PD]<24m from treatment start); late relapse (PD after PFS24). Outcomes for study pts vs gen popn were evaluated using standardized mortality ratios (SMR; deaths in study pts relative to expected deaths in gen popn matched by age, sex, country, and calendar time-at-risk). Expected deaths were derived using the Human Mortality Database, which provides detailed mortality and population data by country and can be used to estimate the background mortality during the observation period. Post-relapse survival in pts with early vs late relapse was assessed using Kaplan-Meier (KM) estimates and Cox regression. QoL was assessed using EQ-5D-3L and UK-based tariffs (Dolan. Med Care 1997); association between QoL and clinical outcomes used a linear mixed-effects model. The proportion of pts with PFS24 reporting QoL problems at baseline and after 24m was compared with age- and country-matched values in the gen popn (Janssen et al. Springer 2014). Data cut-off was Jan 2018 (GOYA final data cut); overall median follow-up was 48m. Results: In the overall IPI 2-5 population, mean age at treatment initiation was 61 yrs. 711 pts reached PFS24, of whom 64 experienced a late relapse (Table 1). Early relapse was experienced by 261 pts, of whom 164 were <6 months from end of treatment (EOT). OS following PFS24 was 98.6% at 2 years (including patients who later relapsed). 2-year PPS was 35.7% for pts with early relapse vs 74.8% for patients with late relapse (Figure 1.) Mortality following PFS24 was 72% of the matched gen popn (SMR 0.72; not significant: 95% CI 0.44-1.11). Mortality following relapse in pts who experienced early relapse was over 33 times higher than expected in the matched gen popn (SMR 33.57, 95% CI 27.69-40.33). However, risk of death following late relapse was reduced by 78% compared with risk following early relapse (HR 0.22 95 CI% 0.12-0.40), and mortality following late relapse was significantly higher than in the matched gen popn (SMR 6.7, 95% CI 3.05-12.67). Mean QoL utility score at baseline was 0.69 for all pts. After pts reached PFS24, estimated mean utility score was 0.86 (95% CI 0.84-0.87) and worsened by -0.07 (95% CI -0.14 to -0.01) at time of subsequent relapse. For early-relapsing pts, the worsening in utility was -0.15 (95% CI -0.20 to -0.10) compared with those still progression-free (Table 2). Among all PFS24 pts at baseline, problems were reported with mobility (28.1%), self-care (12.6%), usual activities (41.8%), pain/discomfort (62.7%), and anxiety/depression (48.8%); these rates were 2.2-4.7 times higher than the gen popn based on age- and country-standardized values. Compared with the gen popn, after pts reached PFS24, pain/discomfort was 10% lower, whereas anxiety/depression was 34% higher and other QoL items were approximately 20% higher. Conclusions: Most of the clinical course of 1L DLBCL occurred ≤2 years after start of treatment. In DLBCL pts with IPI 2-5 achieving PFS24, mortality was similar to the gen popn, and with the exception of mental health metrics, QoL scores were also similar to the gen popn. Late relapse (≥2 yrs) was associated with better post-relapse survival than early relapse (<2 yrs); however, this was inferior to the gen popn. Health state utilities improved whilst patients were relapse-free but the decline in QoL after early relapse was worse than after late relapse. Figure 1 Figure 1. Disclosures Launonen: F. Hoffmann-La Roche Ltd: Current Employment. Ho: F. Hoffmann-La Roche Ltd: Current Employment. Knapp: F. Hoffmann-La Roche Ltd: Current Employment. Canales Ruiz: Clinical Project Manager in Clinica Universidad de Navarra: Current Employment. Simonella: F. Hoffmann-La Roche Ltd: Current Employment. Thuresson: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company.

scholarly journals Clinical Characteristics and Risk of Relapse for Patients with Stage I-II Diffuse Large B-cell Lymphoma Treated in First Line with Immunochemotherapy

2013 ◽  
Vol 6 ◽  
pp. CMBD.S12713
Author(s):  
S. Mercadal ◽  
F. Climent ◽  
E. Domingo-Doménech ◽  
A. Oliveira ◽  
V. Romagosa ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Stage I ◽  
Late Relapse ◽  
First Line ◽  
Early Relapse ◽  
Large B Cell Lymphoma ◽  
Large B Cell ◽  
Risk Of Relapse

Diffuse large b-cell lymphoma (DLBCL) is an aggressive and potentially curable lymphoma that presents itself as stage I-II in 30% of all cases. It is known that in these localized stages, 15-20% of patients treated without rituximab eventually relapse, but less data exist regarding rituximab era. We have analyzed clinico-pathological features and risk of relapse in 98 patients with I-II stage DLBCL in complete response (CR) or unconfirmed CR (CRu) after first-line treatment consisting of immunochemotherapy. Twelve patients (12.2%) eventually relapsed. Late relapse, more than two years after diagnosis, occurred in three patients, and early relapse, less than two years after diagnosis, was documented in nine patients. Median time from diagnosis to relapse was 0.61 years for patients with early relapse and 3.66 years for patients with late relapse. The second CR rate obtained was similar in the late and in early relapsing patients, being 33% versus 44% ( p = 0.072), respectively. Three-year overall survival (OS) was 22% for early relapsing patients and 33% for late relapsing patients ( p = 0.65). In conclusion, patients who are diagnosed with stage I-II DLBCL and achieve a CR/CRu with first line immunochemotherapy have a good prognosis. However, a proportion of patients relapse, and this is less frequent in patients treated with first line with immunochemotherapy. These patients have a poor prognosis.

scholarly journals Late Relapses in Patients With Diffuse Large B-Cell Lymphoma Treated With Immunochemotherapy

2019 ◽  
Vol 37 (21) ◽  
pp. 1819-1827 ◽  
Author(s):  
Yucai Wang ◽  
Umar Farooq ◽  
Brian K. Link ◽  
Melissa C. Larson ◽  
Rebecca L. King ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Late Relapse ◽  
Indolent Lymphoma ◽  
Large B Cell Lymphoma ◽  
Germinal Center B Cell ◽  
Competing Events ◽  
First Relapse ◽  
Large B Cell

PURPOSE In patients with diffuse large B-cell lymphoma (DLBCL), most relapses occur within the first 2 years of diagnosis. We sought to define the rate and outcome of late relapses that occurred after achieving event-free survival at 24 months (EFS24). METHODS We prospectively followed 1,324 patients with newly diagnosed DLBCL from 2002 to 2015 and treated with immunochemotherapy. Cumulative incidences of late DLBCL and indolent lymphoma relapses were analyzed as competing events. Postrelapse survival was defined as time from first relapse to death from any cause. RESULTS In 847 patients who achieved EFS24, the cumulative incidence of late relapse was 6.9% at 3 years, 9.3% at 5 years, and 10.3% at 8 years after EFS24. The incidence of DLBCL relapse was similar in patients with DLBCL alone at diagnosis (6.3% at 5 years), compared with patients with concurrent indolent lymphoma at diagnosis (5.2%; P = .46). However, the rate of indolent lymphoma relapse was higher in patients with concurrent indolent lymphoma (7.4% v 2.1% at 5 years; P < .01). In patients with DLBCL alone, the rate of DLBCL relapse was similar in the germinal center B-cell–like (GCB) (4.1% at 5 years) and non-GCB (4.0%; P = .71) subtypes, whereas the rate of indolent lymphoma relapse was higher in patients with the GCB subtype (3.9% v 0.0% at 5 years; P = .02). Postrelapse survival was inferior for patients who relapsed with DLBCL than for those who relapsed with indolent lymphoma (median 29.9 months v unreached; P < .01). CONCLUSION Patients with DLBCL with a concurrent indolent lymphoma and those with the GCB subtype had a higher rate of late relapse, owing to increased relapses with indolent lymphoma. Patients who relapsed with DLBCL had a worse prognosis than those who relapsed with indolent lymphoma.

scholarly journals The Spectrum of MYC Alterations in Diffuse Large B-Cell Lymphoma

2020 ◽  
Vol 143 (6) ◽  
pp. 520-528
Author(s):  
Yang Xia ◽  
Xinlian Zhang
Keyword(s):  
B Cell ◽  
Clinical Outcomes ◽  
Copy Number ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Genetic Alterations ◽  
Gene Copy ◽  
Novel Therapy ◽  
Large B Cell Lymphoma ◽  
Large B Cell

MYC, as a powerful transcription factor, plays a vital role in various cancers. The clinical significance of MYC alterations in diffuse large B-cell lymphoma (DLBCL) has been investigated for a long time. In this study, we comprehensively summarize the different alterations of MYC in DLBCL, including MYC overexpression, <i>MYC</i> translocations, <i>MYC</i> mutations, and increased gene copy number of <i>MYC</i>. Noteworthy, lone MYC overexpression or <i>MYC</i> translocation is not significantly associated with poor clinical outcomes, and their detrimental effects depend on the genetic alterations of BCL2 or BCL6. Both double-expressor DLBCL (DE-DLBCL), defined as overexpression of MYC and BCL2 proteins, and double-hit lymphoma (DHL), defined as a dual translocation of <i>MYC</i> together with <i>BCL2</i> or <i>BCL6</i>, represent the distinct subgroups of DLBCL with inferior clinical outcomes. The mechanism may be that MYC activation induces cell proliferation, without the threat of the apoptotic brake in the presence of BCL2 overexpression. In addition, most of <i>MYC</i> mutations are present with favorable prognosis, and the nonsignificant effect of MYC copy number amplification has been observed. It has been proved that cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab show limited effects for DHL or DE-DLBCL, and the rituximab plus dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin seem to be efficacious for DHL. The novel therapy is urgently needed for clinical improvement in DHL and DE-DLBCL.

The Impact of Relative Dose Intensity (RDI) of CHOP on Outcome of Diffuse Large B-Cell Lymphoma: Results of a Single Center Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4456-4456
Author(s):  
Yoshiki Terada ◽  
Hirohisa Nakamae ◽  
Takahiko Nakane ◽  
Hideo Koh ◽  
Yasunobu Takeoka ◽  
...  
Keyword(s):  
B Cell ◽  
Clinical Outcomes ◽  
Cell Lymphoma ◽  
Dose Intensity ◽  
B Cell Lymphoma ◽  
Relative Dose Intensity ◽  
Large B Cell Lymphoma ◽  
The Impact ◽  
Large B Cell

Abstract Introduction: The achievement of a clinical response to the first induction chemotherapy has been considered for predicting survival in patients (pts) with aggressive non-Hodgkin lymphoma (NHL). Reduced dose intensity of chemotherapy has been likely to compromise long-term outcome of the patients with aggressive NHL treated with a standard chemotherapy of cyclophosphamide (CY), doxorubicin (ADR), vincristine and prednisone (CHOP). In particular, recent studies have revealed the relevance of relative dose intensity (RDI) to clinical outcomes, with reduced RDI leading to a poor survival, as well as the impact of RDI<85% for aggressive NHL with detailed analysis of risk factors influencing reduce RDI<85% (Gary H. Lyman, J. Clin Oncol22: 4302, 2004). This study was conducted to investigate the impact of RDI<85% of CHOP on outcomes of the pts with diffuse large B-Cell lymphoma (DLCL). Methods: Data were retrospectively collected on 100 pts with DLCL who had been initially treated with more than 3 courses of CHOP (n=70) or CHOP plus rituximab (CHOP-R, n=30) at our institution between 1995 and 2006. We evaluated whether RDI might affect clinical outcomes, including complete response (CR) and event free survival (EFS). The average RDI derived from CY and ADR (referred to as RDI-CY/ADR) was determined for each patient, with classified into 2 populations according to the differences from the value of 85%, including RDI-CY/ADR<85% (n=60), and RDI-CY/ADR≥85% (n=40). Results: The median age of the study population was 54 years (range, 17 to 76), with 36 pts older than 60 years (yrs) of age. According to International Prognostic Index (IPI) score, pts were classified into 2 groups of low/ low-intermediate (n=46) and high/ high-intermediate (n=54). The overall CR rate reached 62%, and the probability of overall survival (OS) or EFS at 5 years estimated 77% or 43%, respectively with a median follow-up of 13.3 months. Multivariate analysis identified RDI-CY/ADR<85%, as well as IPI score to be associated with CR rate and EFS. Thus, RDI-CY/ADR<85% and IPI score of high/ high-intermediate were significant factors for lower CR rate (as RDI-CY/ADR≥85%, HR=0.3, 95% CI 0.1 to 0.7, p=0.009, and HR=5.5, 95% CI 2.2 to 14, p<0.001, respectively), and for reduced EFS (HR=1.9, 95% CI 1.0 to 3.7, p=0.048, and as IPI score of low/ low-intermediate HR=0.3, 95% CI 0.2 to 0.6, p<0.001, respectively). Furthermore, logrank analysis revealed that CY/ADR-RDI<85% was the significant factor for reduced EFS in non elderly pts (≤60 yrs of age), or in pts with IPI score of low/ low-intermediate (p=0.01, p=0.02, respectively). Conclusion: These data thus suggested the impact of RDI-CY/ADR<85% in influencing outcomes of the pts with DLCL, in terms of CR rate and EFS. Further investigation is currently planned to confirm this promising results with longer follow-up in larger numbers of pts with NHL.

Lymphoma recurrence 5 years or more following diffuse large B-cell lymphoma: Clinical characteristics and outcome

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8562-8562
Author(s):  
J. Larouche ◽  
F. Berger ◽  
C. Chassagne-Clement ◽  
C. Sebban ◽  
H. Ghesquieres ◽  
...  
Keyword(s):  
B Cell ◽  
Clinical Characteristics ◽  
Cell Lymphoma ◽  
Autologous Transplantation ◽  
B Cell Lymphoma ◽  
Stage I ◽  
Late Relapse ◽  
Extranodal Involvement ◽  
Large B Cell Lymphoma ◽  
Large B Cell

8562 Background: Diffuse large B-cell lymphoma (DLBCL) usually relapses early following treatment but some relapses happen 5 years or later. Few data exist regarding clinical characteristics and outcome of these patients (pts). Methods: We performed a retrospective analysis of all pts from two centers in Lyon/France between 1980–2003 who presented a biopsy proven relapse 5 years or later following diagnosis of DLBCL. All available biopsies were revised and immunohistochemistry (IHC) completed. Results: Among 1492 pts with DLBCL, 54 were eligible. Clinical characteristics at diagnosis were: median age 57 y; stage I-II 63% (34/54); IPI low/low intermediate 84% (41/49) and extranodal involvement (EN) 66% (35/53). IHC at diagnosis: CD20 100% (46/46), CD10 28% (10/36), bcl-6 53% (9/17), MUM1 48% (11/23), bcl-2 68% (19/28), germinal-center phenotype (GC) 57% (12/21) and non-GC 43% (9/21). 47/53 received CHOP/ACVBP-like regimens, 1 autologous transplantation (ASCT) and 1 rituximab. Median time from diagnosis to relapse was 7.4 years (5–20.5 years). 44 pts (81%) had DLBCL histology at time of relapse and 10 pts (19%) indolent histology. MUM1 expression at diagnosis was associated with DLBCL histology at relapse (p=0.037). Clinical characteristics at relapse were: median age 66 y; stage I-II 48% (26/54); 73% (31/43) with DLBCL at relapse had EN. 54% (15/28) with DLBCL at relapse had a GC phenotype and 46% (13/28) a non-GC phenotype. Treatment at relapse included rituximab in 21/54 and ASCT in 15/54 with 7 pts receiving both. Estimated 5-year event-free survival (EFS) and overall survival (OS) after relapse were 25% and 35% for all pts. Pts with DLBCL histology at relapse had an estimated 5-year EFS and OS of 18% and 28%. Pts with indolent histology had an estimated 5-year EFS and OS of 55% and 67%. Conclusions: Patients with DLBCL who present a late relapse usually had localized stage, favorable IPI and extranodal involvement at diagnosis. However, even if initial characteristics at time of first treatment were favorable, outcome of pts with DLBCL at time of relapse remains poor and aggressive treatment, such as ASCT, should be pursue whenever possible. Some patients relapsed with indolent histology and have a better outcome. No significant financial relationships to disclose.

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