Inferior progression-free survival for Thai patients with diffuse large B-cell lymphoma treated under Universal Coverage Scheme: the impact of rituximab inaccessability

Abstract Abstract 2676 Purpose Akt is a serine/threonine kinase that plays a central role in cell proliferation and growth. To define clinical impact of Akt expression in diffuse large B-cell lymphoma(DLBCL), we investigated the expression of phospho-Akt(p-Akt) in DLBCL and analyzed clinical impact of p-Akt expression on patient survival. Methods We evaluated the p-Akt expression in 99 DLBCL patients using tissue microarray(TMA) technology. Results Positive p-Akt expression was observed in 15.2% of the patients and significantly associated with elevated lactic dehydrogenase level (P = .044). Kaplan-Meier survival analysis showed that the patients with positive p-Akt expression showed substantially poorer overall survival (p-Akt+ vs p-Akt- 25.3 months [95% confidence interval(CI), 14.4–36.2 months] vs 192.6 months [95% CI, 131.3–253.9 months], P < .001) and progression-free survival (p-Akt+ vs p-Akt- 13.6 months[95% CI, 14.4–36.2 months] vs 134.5 months [95% CI, 131.3–253.9 months], P < .001), respectively. Multivariate Cox regression analysis revealed that patients with DLBCL with p-Akt positivity showed poorer overall survival with 3.2 fold (95% CI, 1.6–6.8, P = .002) risk for death compared to patients with DLBCL with p-Akt negativity. Conclusion Positive expression of p-Akt in DLBCL patients is associated with poorer overall and progression-free survival. Expression of p-Akt may act as an independent poor prognostic factor and might be a novel therapeutic target for DLBCL. Disclosures: No relevant conflicts of interest to declare.

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18F-FDG cerebellum/liver index as a prognostic factor for progression-free survival in diffuse large B-cell lymphoma

Annals of Nuclear Medicine ◽

10.1007/s12149-021-01609-4 ◽

2021 ◽

Author(s):

David Morland ◽

Ghali Zizi ◽

François Godard ◽

Anne-Cécile Gauchy ◽

Carole Durot ◽

...

Keyword(s):

Prognostic Factor ◽

B Cell ◽

Cell Lymphoma ◽

Progression Free Survival ◽

B Cell Lymphoma ◽

Free Survival ◽

Liver Index ◽

Large B Cell Lymphoma ◽

18F Fdg ◽

Large B Cell

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Rituximab-CHOP With Early Rituximab Intensification for Diffuse Large B-Cell Lymphoma: A Randomized Phase III Trial of the HOVON and the Nordic Lymphoma Group (HOVON-84)

Journal of Clinical Oncology ◽

10.1200/jco.19.03418 ◽

2020 ◽

Vol 38 (29) ◽

pp. 3377-3387

Author(s):

Pieternella Johanna Lugtenburg ◽

Peter de Nully Brown ◽

Bronno van der Holt ◽

Francesco A. D’Amore ◽

Harry R. Koene ◽

...

Keyword(s):

B Cell ◽

Cell Lymphoma ◽

Progression Free Survival ◽

B Cell Lymphoma ◽

Standard Of Care ◽

Phase Iii ◽

Free Survival ◽

Intention To Treat ◽

Large B Cell Lymphoma ◽

Large B Cell

PURPOSE Immunochemotherapy with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has become standard of care for patients with diffuse large B-cell lymphoma (DLBCL). This randomized trial assessed whether rituximab intensification during the first 4 cycles of R-CHOP could improve the outcome of these patients compared with standard R-CHOP. PATIENTS AND METHODS A total of 574 patients with DLBCL age 18 to 80 years were randomly assigned to induction therapy with 6 or 8 cycles of R-CHOP-14 with (RR-CHOP-14) or without (R-CHOP-14) intensification of rituximab in the first 4 cycles. The primary end point was complete remission (CR) on induction. Analyses were performed by intention to treat. RESULTS CR was achieved in 254 (89%) of 286 patients in the R-CHOP-14 arm and 249 (86%) of 288 patients in the RR-CHOP-14 arm (hazard ratio [HR], 0.82; 95% CI, 0.50 to 1.36; P = .44). After a median follow-up of 92 months (range, 1-131 months), 3-year failure-free survival was 74% (95% CI, 68% to 78%) in the R-CHOP-14 arm versus 69% (95% CI, 63% to 74%) in the RR-CHOP-14 arm (HR, 1.26; 95% CI, 0.98 to 1.61; P = .07). Progression-free survival at 3 years was 74% (95% CI, 69% to 79%) in the R-CHOP-14 arm versus 71% (95% CI, 66% to 76%) in the RR-CHOP-14 arm (HR, 1.20; 95% CI, 0.94 to 1.55; P = .15). Overall survival at 3 years was 81% (95% CI, 76% to 85%) in the R-CHOP-14 arm versus 76% (95% CI, 70% to 80%) in the RR-CHOP-14 arm (HR, 1.27; 95% CI, 0.97 to 1.67; P = .09). Patients between ages 66 and 80 years experienced significantly more toxicity during the first 4 cycles in the RR-CHOP-14 arm, especially neutropenia and infections. CONCLUSION Early rituximab intensification during R-CHOP-14 does not improve outcome in patients with untreated DLBCL.

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Real-world practice patterns and outcomes in Veterans with relapsed/refractory diffuse large B-cell lymphoma

Future Oncology ◽

10.2217/fon-2020-0522 ◽

2020 ◽

Author(s):

Hsu-Chih Chien ◽

Deborah Morreall ◽

Vikas Patil ◽

Kelli M Rasmussen ◽

Chunyang Li ◽

...

Keyword(s):

Overall Survival ◽

B Cell ◽

Cell Lymphoma ◽

Progression Free Survival ◽

B Cell Lymphoma ◽

Line Treatment ◽

Electronic Health Record Data ◽

Free Survival ◽

Large B Cell Lymphoma ◽

Large B Cell

Aim: To describe practices and outcomes in veterans with relapsed/refractory diffuse large B-cell lymphoma. Patients & methods: Using Veteran Affairs Cancer Registry System and electronic health record data, we identified relapsed/refractory diffuse large B-cell lymphoma patients completing second-line treatment (2L) in 2000–2016. Treatments were classified as aggressive/nonaggressive. Analyses included descriptive statistics and the Kaplan–Meier estimation of progression-free survival and overall survival. Results: Two hundred and seventy patients received 2L. During median 9.7-month follow-up starting from 2L, 470 regimens were observed, averaging 2.7 regimens/patient: 219 aggressive, 251 nonaggressive. One hundred and twenty-one patients proceeded to third-line, 50 to fourth-line and 18 to fifth-line treatment. Median progression-free survival in 2L was 5.2 months. Median overall survival was 9.5 months. Forty-four patients (16.3%) proceeded to bone marrow transplant. Conclusion: More effective, less toxic treatments are needed and should be initiated earlier in treatment trajectory.

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Diffuse Large B-Cell Lymphoma Classification System That Associates Normal B-Cell Subset Phenotypes With Prognosis

Journal of Clinical Oncology ◽

10.1200/jco.2014.57.7080 ◽

2015 ◽

Vol 33 (12) ◽

pp. 1379-1388 ◽

Cited By ~ 52

Author(s):

Karen Dybkær ◽

Martin Bøgsted ◽

Steffen Falgreen ◽

Julie S. Bødker ◽

Malene K. Kjeldsen ◽

...

Keyword(s):

B Cell ◽

Classification System ◽

Cell Lymphoma ◽

Positive Impact ◽

Cell Subset ◽

Progression Free Survival ◽

B Cell Lymphoma ◽

Large B Cell Lymphoma ◽

The Impact ◽

Large B Cell

Purpose Current diagnostic tests for diffuse large B-cell lymphoma use the updated WHO criteria based on biologic, morphologic, and clinical heterogeneity. We propose a refined classification system based on subset-specific B-cell–associated gene signatures (BAGS) in the normal B-cell hierarchy, hypothesizing that it can provide new biologic insight and diagnostic and prognostic value. Patients and Methods We combined fluorescence-activated cell sorting, gene expression profiling, and statistical modeling to generate BAGS for naive, centrocyte, centroblast, memory, and plasmablast B cells from normal human tonsils. The impact of BAGS-assigned subtyping was analyzed using five clinical cohorts (treated with cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP], n = 270; treated with rituximab plus CHOP [R-CHOP], n = 869) gathered across geographic regions, time eras, and sampling methods. The analysis estimated subtype frequencies and drug-specific resistance and included a prognostic meta-analysis of patients treated with first-line R-CHOP therapy. Results Similar BAGS subtype frequencies were assigned across 1,139 samples from five different cohorts. Among R-CHOP–treated patients, BAGS assignment was significantly associated with overall survival and progression-free survival within the germinal center B-cell–like subclass; the centrocyte subtype had a superior prognosis compared with the centroblast subtype. In agreement with the observed therapeutic outcome, centrocyte subtypes were estimated as being less resistant than the centroblast subtype to doxorubicin and vincristine. The centroblast subtype had a complex genotype, whereas the centrocyte subtype had high TP53 mutation and insertion/deletion frequencies and expressed LMO2, CD58, and stromal-1–signature and major histocompatibility complex class II–signature genes, which are known to have a positive impact on prognosis. Conclusion Further development of a diagnostic platform using BAGS-assigned subtypes may allow pathogenetic studies to improve disease management.

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Negative effect of hepatitis in overall and progression-free survival among patients with diffuse large B-cell lymphoma

Infectious Agents and Cancer ◽

10.1186/s13027-018-0190-9 ◽

2018 ◽

Vol 13 (1) ◽

Cited By ~ 4

Author(s):

Mubarak M. Al-Mansour ◽

Saif A. Alghamdi ◽

Musab A. Alsubaie ◽

Abdullah A. Alesa ◽

Muhammad A. Khan

Keyword(s):

B Cell ◽

Cell Lymphoma ◽

Progression Free Survival ◽

B Cell Lymphoma ◽

Free Survival ◽

Large B Cell Lymphoma ◽

Negative Effect ◽

Large B Cell

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Survival of Limited Stage Peripheral T-Cell Lymphoma Is Similar To Diffuse Large B-Cell Lymphoma.

Blood ◽

10.1182/blood.v106.11.2817.2817 ◽

2005 ◽

Vol 106 (11) ◽

pp. 2817-2817 ◽

Cited By ~ 1

Author(s):

Kerry J. Savage ◽

Mukesh Chhanabhai ◽

Nicholas Voss ◽

Shenkier Tamara ◽

Randy D. Gascoyne ◽

...

Keyword(s):

Overall Survival ◽

T Cell ◽

B Cell ◽

Cell Lymphoma ◽

Progression Free Survival ◽

B Cell Lymphoma ◽

Free Survival ◽

Limited Stage ◽

Large B Cell Lymphoma ◽

Large B Cell

Abstract Background: Peripheral T-cell lymphomas (PTCL) represent a heterogeneous group of diseases with an overall poor prognosis. Little information is available regarding the outcome of PTCL patients who present with limited stage disease. We sought to determine the outcome of PTCL patients presenting with limited disease in comparison with a cohort of patients with limited stage diffuse large B-cell lymphoma (DLBCL). Methods: In a retrospective analysis we identified all patients with limited stage (non-bulky (<10cm) stage I/II disease no symptoms) PTCL diagnosed at the British Columbia Cancer Agency (BCCA) between 1983 and 2004. Patients were excluded if they had cutaneous anaplastic large cell lymphoma (CutALCL) (n=13), NK/T-cell lymphoma nasal type (n=9) or primary CNS/ocular involvement (n=6). Results: Thirty-seven patients with PTCL were identified according to the World Health Organization Classification: ALK-neg ALCL 8 (22%); PTCL-unspecified (PTCLUS) 28 (78%); enteropathy associated TCL (EATL) 1 (3 %). The majority received CHOP-type chemotherapy (n=31, 86%), most with brief chemotherapy followed by involved-field radiation (n=19, 61%). The 5 y OS and PFS was similar between PTCLUS and ALK-neg ALCL. There was no difference in survival between extranodal and nodal cases. The outcome of PTCL patients (including ALK-neg ALCL and PTCLUS) was compared to a cohort of limited stage DLBCL patients (excluding CNS/ocular lymphoma) (n=305) diagnosed over the same time period and treated similarly. There was no difference in 5 y OS or PFS (Figure 1,2). Interestingly, there were no late relapses observed in PTCLUS, in marked contrast to DLBCL. Conclusions: Limited stage PTCL is rare, however outcomes appear to be comparable to early stage DLBCL, supporting that they should be treated in a similar manner. Unlike limited stage DLBCL where late relapses occur, a plateau in the progression-free survival curve is observed, highlighting a distinct natural history for limited stage PTCL. Overall Survival Limited Stage PTCL vs DLBCL p=.18 Overall Survival Limited Stage PTCL vs DLBCL p=.18 Progression-Free Survival Limited Stage PTCL vs DLBCL p=.07 Progression-Free Survival Limited Stage PTCL vs DLBCL p=.07

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Significance of c-myc Rearrangements in Diffuse Large B-Cell Lymphoma.

Blood ◽

10.1182/blood.v108.11.2030.2030 ◽

2006 ◽

Vol 108 (11) ◽

pp. 2030-2030

Author(s):

Philip Bierman ◽

Fausto Loberiza ◽

Bhavana Dave ◽

Warren Sanger ◽

R. Gregory Bociek ◽

...

Keyword(s):

Overall Survival ◽

B Cell ◽

Cell Lymphoma ◽

Survival Rates ◽

Progression Free Survival ◽

B Cell Lymphoma ◽

Free Survival ◽

Large B Cell Lymphoma ◽

Large B Cell ◽

Overall Survival Rates

Abstract Rearrangements of the c-myc oncogene can be seen in 5–10% of patients with diffuse large B-cell lymphoma. However, studies examining the significance of this finding have yielded conflicting results. Therefore, we performed a retrospective analysis to determine the clinical significance of c-myc rearrangements in diffuse large B-cell lymphoma. The results of classical cytogenetic studies and FISH analyses were used to identify diffuse large B-cell lymphoma cases in the database of the Nebraska Lymphoma Study Group with or without c-myc rearrangements. Patients who were HIV positive and those with post-transplant lymphoproliferative disease were excluded. We identified 16 patients with diffuse large B-cell lymphoma and c-myc rearrangements. All patients were initially treated with doxorubicin- or mitoxantrone-containing chemotherapy regimens. The median age of these 16 patients was 61 years (range 40 to 80), and 5 (31%) were males. The International Prognostic Index (IPI) was 0–2 at diagnosis in 9 patients (56%), and 3–5 in 7 patients (44%). Eleven patients (69%) had bulky disease (≥ 5 cm) at diagnosis. No significant differences in outcome were identified when the 16 c-myc positive patients were compared with 97 c-myc negative diffuse large B-cell lymphoma patients in the same age range. The actuarial 5-year progression-free survival for the c-myc positive patients was 23% (95% CI 6% to 46%), as compared with 38% (95% CI 29% to 48%) for c-myc negative patients (p=0.17). The actuarial 5-year overall survival rates were 36% (95% CI 14% to 59%) and 47% (95% CI 36% to 56%), respectively (p=0.19). Classical cytogenetics and FISH analyses were also used to examine the 16 c-myc positive cases for bcl-2 rearrangements. Eight (50%) cases had rearrangements of bcl-2 in addition to c-myc rearrangements. These patients were similar to the c-myc positive/bcl-2 negative patients except for a higher likelihood of an elevated LDH level at diagnosis (88% vs. 25%; p=0.03). The actuarial 5-year progression-free survival for c-myc positive/bcl-2 positive patients was 0%, as compared to 33% (95% CI 6% to 66%) for patients with rearrangements of c-myc alone, and 37% (95% CI 28% to 47%) for c-myc negative patients. The actuarial 5-year overall survival rates were 12% (95% CI 1% to 42%), 47% (95% CI 12% to 76%), and 41% (95% CI 31% to 51%), respectively. A multivariate analysis, adjusting for IPI score, demonstrated that the relative risk (RR) of treatment failure was significantly worse for the c-myc positive/bcl-2 positive patients, as compared to the c-myc negative patients (RR 2.86, 95% CI 1.32–6.23; p=0.008). Similarly, mortality was also significantly worse for the c-myc positive/bcl-2 positive patients, as compared to the c-myc negative patients (RR 2.69, 95% CI 1.18–6.11; p=0.02). In contrast, no significant differences in treatment failure or overall survival were demonstrated when c-myc positive/bcl-2 negative patients were compared with c-myc negative patients. Our results demonstrate that the c-myc rearrangement is not associated with poorer survival in patients with diffuse large B-cell lymphoma. However, patients with rearrangements of bcl-2 in addition to c-myc had significantly worse progression-free survival and overall survival.

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