R-CHOP compared with CHOP in patients with diffuse large B-cell lymphoma (DLCL): Russian experience

18536 Background: R-CHOP is regarded as the best available treatment for untreated patients with aggressive and indolent B- NHL. Methods: 184 previously untreated patients with DLCL were included in retrospective study: 92 patients were treated by CHOP, 92 patients were treated by CHOP plus rituximab ( R-CHOP ). Age of patients ranged 16–87 years (median 50 years). The median follow- up was 18 months. Compared groups were balanced in all parameters. The advanced stage of disease (III-IV) at diagnosis had 66% patients treated with CHOP and 67,5 % patients treated with R-CHOP. =2 extranodal zones were initially revealed at 35% in CHOP group vs 47% in R- CHOP group. PS of 25 % patients in R-CHOP group and 30% patients in CHOP group was regarded as appropriate 3–4 degrees on ECOG. Increased LDH level was marked at 60% in CHOP-group vs 54% in R-CHOP. 29% patients in R-CHOP group and 21% patients in CHOP group had B-symptoms at diagnosis; bulky disease took place in 53% cases in R-CHOP group and 62% cases in CHOP. High IPI score had 47 % patients in CHOP-group vs 48 % in R-CHOP. Results: Complete response was achieved in 74% of the patients treated with R- CHOP, as compared to 56% of those treated with CHOP alone (p<0,05). Disease progression during treatment was reported in 25% of patients in CHOP group and 18,5% in R-CHOP group. Median overall survival in patients treated with R-CHOP was NS, in patients treated with CHOP alone was 16 months. With a median follow-up of 18 months, 29 (31,5%) events (progression - 18,5%, relapse - 10%, death - 3% ) were observed in the R-CHOP group and 48 (52%) events ( progression - 25%, relapse - 20%, death - 7%) in the CHOP group (p<0,05). Median event-free survival and relapse-free survival in the CHOP group was 12 months, in R-CHOP group NS. Toxicity was equivalent in both groups. Conclusions: We have established better direct efficiency and outcome of R-CHOP in any age of pts. No significant financial relationships to disclose.

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Clinical Outcomes of R-CHOP Chemotherapy Alone Compared with R-CHOP Plus Radiotherapy in Patients with Localized, Non-Bulky Diffuse Large B-Cell Lymphoma

Blood ◽

10.1182/blood.v124.21.4421.4421 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4421-4421

Author(s):

Ji Hyun Park ◽

Dok Hyun Yoon ◽

Shin Kim ◽

Jung Sun Park ◽

Sang-wook Lee ◽

...

Keyword(s):

Overall Survival ◽

Clinical Outcomes ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Complete Response ◽

Event Free Survival ◽

Chop Chemotherapy ◽

Free Survival ◽

Large B Cell Lymphoma ◽

Clinicopathologic Parameters

Abstract Introduction Although several previous studies addressed the role of radiation in treating localized diffuse large B-cell lymphoma (DLBCL), chemotherapy alone has shown promising efficacy with the emergence of Rituximab. Thus, we evaluated the clinical efficacy outcomes and failure patterns of patients with localized DLBCL according to two different treatment strategies, either 6 or more cycles of R-CHOP chemotherapy alone or 3 or 4 cycles of R-CHOP followed by involved field radiotherapy (IFRT). Methods A prospectively collected database from 21 tertiary centers participating the Consortium for Improving Survival of Lymphoma (CISL), built up for PROCESS study (NCT01202448) for secondary central nervous system involvement in DLBCL, was recruited for current study in addition to the Asan Medical Center (AMC) Lymphoma Registry. CISL database and AMC lymphoma registry consisted of data from patients with newly diagnosed DLBCL between August 2010 and August 2012, and between February 2004 and February 2012, respectively. Inclusion criteria were localized (stage I or II), non-bulky (<10cm in longest diameter) DLBCL treated with R-CHOP as 1st line chemotherapy, and patients either who received 6 or more cycles of R-CHOP chemotherapy only (R-CHOP alone group) or received 3 or 4 cycles of R-CHOP chemotherapy followed by IFRT (R-CHOP plus RT group). Comparisons of clinicopathologic parameters, clinical outcomes and the patterns of relapse were performed between two groups. The types of relapse were classified as either locoregional or distant, according to whether it involves any separate region from primary sites. Efficacy outcomes included complete response (CR) rate, 2-year overall survival (OS) rate, and 2-year event-free survival (EFS) rate. Results A total of 357 patients (CISL prospective cohort: 161 patients, AMC registry: 196 patients) were eligible for the analyses. Two hundred ninety nine patients (83.5%) received 6 or more cycles of R-CHOP chemotherapy alone, and 58 patients (16.2%) underwent 3 or 4 cycles of R-CHOP followed by IFRT. Median age was 54 years (range, 16-87). During the median follow-up of 24 months (range, 4-116 months), 35 patients (9.8%) experienced relapse, and 22 patients (6.1%) died. Two-year OS and EFS rate was 94.7% and 89.9%, respectively, and 345 out of 357 patients (96.6%) achieved CR. Comparing R-CHOP alone to R-CHOP plus RT group, there was no significant difference in clinicopathologic parameters. R-CHOP alone could achieve significantly higher CR rate of 97.7 % than 91.4% of R-CHOP plus RT group (p = 0.030). Two-year OS and EFS were significantly longer in R-CHOP alone group than R-CHOP plus RT group (96.1 vs 89.9 %, p = 0.029 and 91.7% vs 81.8%, p= 0.028) (Figure 1). Relapse rate was significantly lower in R-CHOP alone group compared with R-CHOP plus RT group than group (7.4% vs 22.4%, p=0.001), and distant relapses were also significantly lower (15.5% vs 2.7%, p<0.001). In addition, even only in relapsed patients, R-CHOP alone group showed lower incidence of distant relapses with marginal statistical significance (36.4% vs 69.2 %, p=0.062) (Table 1). Conclusion In our cohort, R-CHOP alone for six to eight cycles without IFRT could achieve significantly higher 2-year OS and EFS rate as well as CR compared with R-CHOP plus RT group. In addition, the rate of relapse and systemic failure were significantly lower in R-CHOP alone group, which altogether warrant further validation in prospective trial. Table 1. Explorative comparison of overall clinical outcomes and patterns of relapse between two subgroups: patients who underwent six or more cycles of R-CHOP chemotherapy alone and who underwent 3 or 4 cycles of R-CHOP followed by IFRT Total (%) R-CHOP alone group (%) R-CHOP plus RT group (%) P -value Number of patients 357 (100) 299 (83.5) 58 (16.2) Treatment response Complete response 345 (96.6) 292 (97.7) 53 (91.4) 0.030 Overall response 351 (98.3) 294 (98.3) 57 (98.3) 1.000 Rate of relapse 35 (9.8%) 14 (7.4) 11 (22.4) < 0.001 Median time to relapse (95% CI) 11 (7-15) 11 (8-14) 10 (5-14) 0.346 Pattern of relapse < 0.001 (0.062) Locoregional 14 (4.7) (63.6) 4 (6.9) (30.8) Distant 8 (2.7) (36.4) 9 (15.5) (69.2) Figure 1. Comparison of overall survival and event-free survival in two subgroups: patients who underwent six or more cycles of R-CHOP chemotherapy alone and who underwent 3 or 4 cycles of R-CHOP followed by IFRT Figure 1. Comparison of overall survival and event-free survival in two subgroups: patients who underwent six or more cycles of R-CHOP chemotherapy alone and who underwent 3 or 4 cycles of R-CHOP followed by IFRT Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

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Improved Progression-Free Survival for Bulky and Non-Bulky Advanced Stage Diffuse Large B-Cell Lymphoma with Consolidative Radiation Therapy: A Bi-Institutional Analysis

10.21203/rs.3.rs-137697/v1 ◽

2021 ◽

Author(s):

Yusef Ali Syed ◽

Cecilia Jiang ◽

Jeffrey Switchenko ◽

Khadija Kirmani ◽

Chris Kelsey ◽

...

Keyword(s):

Systemic Therapy ◽

Cell Lymphoma ◽

Progression Free Survival ◽

B Cell Lymphoma ◽

Complete Response ◽

Stage Iii ◽

Bulky Disease ◽

Free Survival ◽

Large B Cell Lymphoma

Abstract Background: The role of consolidative radiation therapy (RT) for advanced stage diffuse large B-cell lymphoma (DLBCL) is not fully established. Retrospective data provide evidence for the use of consolidative RT in stage III-IV DLBCL and emerging data from randomized studies address the role of RT in bulky disease for these patients.Methods: Patient with stage III-IV DLBCL treated at two institutions who achieved clinical complete response to systemic therapy were included. Kaplan-Meier analysis was performed to determine the impact of consolidative RT. Univariate and multivariable analyses were performed using a Cox proportional hazards model.Results: One hundred eighty-eight patients received systemic therapy consisting of R-CHOP (79%), another Rituximab-based regimen (9%), or chemotherapy alone (12%). Clinical response was assessed using conventional CT or PET-CT. Sixty-eight patients (36%) received consolidative RT (median dose 30 Gy). Consolidative RT conferred a 36.7% absolute benefit in five-year progression-free survival (85.9% vs. 49.2%, log rank p < 0.0001), and a 14.5% absolute benefit in five-year overall survival (87.4% vs. 72.9%, log rank p = 0.0134). On multivariable analysis, consolidative RT was associated with improved PFS (HR 0.23, 95% CI 0.10-0.52, p < 0.001). Patients receiving consolidative RT demonstrated significantly improved PFS for tumors measuring both <5 cm (log rank p = 0.0454) and ³5 cm (log rank p = 0.0003).Conclusions: For patients with stage III-IV DLBCL who achieve clinical complete response after systemic therapy, consolidative RT improves PFS for all patients, including those with non-bulky disease. This benefit persists in the setting of rituximab-based systemic therapy.

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Patients with aaIPI 2-3 Diffuse Large B-Cell Lymphoma Achieve 75% Long-Term Survival Following First-Line Rituximab-Supplemented High-Dose Sequential Chemotherapy and Autograft: Final Results of the Prospective Phase II GITIL (Gruppo Italiano Terapie Innovative nei Linfomi) Trial.

Blood ◽

10.1182/blood.v110.11.1889.1889 ◽

2007 ◽

Vol 110 (11) ◽

pp. 1889-1889 ◽

Cited By ~ 1

Author(s):

Corrado Tarella ◽

Manuela Zanni ◽

Massimo Di Nicola ◽

Caterina Patti ◽

Claudia Castellino ◽

...

Keyword(s):

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

High Dose ◽

Event Free Survival ◽

First Line ◽

Sequential Chemotherapy ◽

Free Survival ◽

Large B Cell Lymphoma

Abstract Background The outcome of Diffuse Large B Cell Lymphoma (DLB-CL) has been definitely improved by the addition of the anti-CD20 rituximab to conventional chemotherapy. However, despite the advantages offered by rituximab, results are still disappointing in patients presenting with adverse prognostic factors. For these patients, rituximab-supplemented intensive programs with autograft might represent a suitable option. Thus, a prospective multicenter study has been performed using first-line the Rituximab-supplemented high-dose sequential chemotherapy program delivered with multiple autologous peripheral blood progenitor cell (PBPC) support (R-HDS-maps regimen), in DLB-CL patients with score 2 or 3 according to the age-adjusted International Prognostic Index (aaIPI). Preliminary results have been already reported (ASH 2005; Leukemia2007, 21: 1802). Updated results after a prolonged follow-up are here presented. Methods. R-HDS-maps includes: 3 APO courses; sequential administration of hd-cyclophosphamide (CY), hd-Ara-C, both supplemented with Rituximab, hd-etoposide/Cisplatin, with PBPC harvests following hd-CY and hd-Ara-C; hd-Mitoxantrone/L-Pam + 2 further Rituximab doses; involved-field radiotherapy. PBPC rescue was scheduled following Ara-C, etoposide/Cisplatin and Mitoxantrone/L-Pam. Six GITIL Centers participated in the multicenter study, with patients enrolled between November 1999 and September 2004. Results. Overall, 112 consecutive patients (74 score 2, 38 score 3) entered the study protocol. There were 5 early toxic deaths (3 sepsis, 1 pneumonia, 1 JC-virus leucoencephalopathy) + one late toxic death due to pneumonia, at 10 mos.; two more patients died for secondary myelodysplastic syndrome at 3.4 and 3.6 yrs. As reported in Figures 1–2, at a median follow-up of 59 mos., 86 patients (77%) are alive; 79 (70%) are in continuous CR, with a 5-yr event-free survival (EFS) projections of 69%; no significant differences in OS and EFS between subgroups with Germinal-Center and Activated B-cell phenotype were observed. Conclusions. R-HDS-maps regimen: is feasible in a multicenter setting, with a toxicity similar to that of other dose-intense/high-dose regimens; offers prolonged survival to most patients with aaIPI 2–3 DLB-CL. Its comparative efficacy versus R-CHOP-14 is being tested in an ongoing GITIL phase III study. Figure 1 . Overall Survival of 112 aaIPI DLB-CL Figure 1. . Overall Survival of 112 aaIPI DLB-CL Figure 2. Event-free Survival according to GC and ABC phenotype Figure 2. Event-free Survival according to GC and ABC phenotype

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Vitamin D Deficiency Is Associated with Inferior Event-Free and Overall Survival in Diffuse Large B-Cell Lymphoma.

Blood ◽

10.1182/blood.v114.22.1952.1952 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1952-1952

Author(s):

Matthew T Drake ◽

Matthew J Maurer ◽

Brian K Link ◽

Ivana N Micallef ◽

Thomas M Habermann ◽

...

Keyword(s):

Clinical Trial ◽

Vitamin D ◽

Overall Survival ◽

Vitamin D Deficiency ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Event Free Survival ◽

Free Survival ◽

Large B Cell Lymphoma

Abstract Abstract 1952 Poster Board I-975 Background: Vitamin D is a naturally occurring steroid hormone. In addition to its well-established role in maintaining serum calcium homeostasis, vitamin D has effects on cellular differentiation, proliferation, apoptosis, and angiogenesis. Vitamin D3 is naturally produced in skin in response ultraviolet-B (UVB) radiation from the sun. Several recent studies, however, have shown that a high proportion of community-dwelling subjects in both tropical and temperate climates are deficient in vitamin D, and that subjects in northern latitudes often require dietary supplementation to maintain vitamin D sufficiency. Further, several reports now suggest that vitamin D sufficiency is protective against the development of several cancers, including non-Hodgkin lymphoma (NHL). However, it is not known whether vitamin D impacts prognosis in diffuse large B-cell lymphoma (DLBCL), the most common NHL subtype. Methods: We evaluated serum vitamin D concentrations in two cohorts of DLBCL patients. The first cohort consisted of 374 patients newly diagnosed from September 2002-February 2008 who were prospectively enrolled in the University of Iowa/Mayo Clinic Lymphoma SPORE Molecular Epidemiology Resource, an observational study in which neither therapeutic nor diagnostic management is prescribed. All serum was obtained within 120 days of diagnosis, and was prior to treatment in 221 (59%). In the second study, 62 patients newly diagnosed from February 2006-August 2007 were enrolled on NCCTG clinical trial N0489, and all serum was obtained before the first course of therapy. Central pathology review was performed on all patients to confirm the diagnosis of DLBCL. Serum 25-hydroxyvitamin (25-OH-VitD) levels were measured by the gold standard method for vitamin D determination: liquid chromatography tandem mass spectroscopy (LC-MS/MS). Vitamin D deficiency was defined as total serum 25-OH-VitD < 25 ng/mL (62.5 nmol/L). SPORE patients were followed per a standard protocol for event-free (progression, retreatment, or death due to any cause) and overall survival (EFS and OS, respectively); N0489 patients were followed in a similar way per the clinical trial protocol. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CI). Results: SPORE patients were primarily treated with immunochemotherapy (83%); all N0489 patients were treated with epratuzumab + R-CHOP21. The median age at diagnosis was 62 years (range, 19-93) for SPORE patients and 61 years (range, 21-82) for N0489 patients. Median follow-up for SPORE patients was 36 months (range, 1-77) with 95 deaths and 131 events; median follow-up for N0489 patients was 24 months (range, 7-39) with 13 deaths and 18 events. Vitamin D deficiency was identified in 188 SPORE patients (50%) and 15 N0489 patients (24%). There were no differences in the prevalence of vitamin D deficiency by age, IPI, or whether serum was obtained prior to starting treatment (all p > 0.28). Vitamin D deficiency was associated with inferior overall (HR=2.33, 95% CI 1.53-3.57, logrank p = 0.0001) and event-free survival (HR=1.71, 95% CI 1.20-2.44, logrank p = 0.003) in the SPORE cohort. These associations remained significant after adjusting for IPI and treatment: OS HR=1.97, 95% CI 1.27-3.07; EFS HR=1.47, 95% CI 1.02-2.21. These results were similar for the subset of SPORE patients who were treated with R-CHOP. The HRs for vitamin D deficiency and event-free survival were consistent in the N0489 patients (HR=1.63, 95% CI 0.61-4.35, IPI adjusted HR=1.43, 95% CI 0.53-3.85), although these results lacked precision due to a smaller sample size. We were unable to evaluate OS in N0489 due to the small number of deaths. Conclusions: Approximately 50% of all DLBCL patients in this northern US latitude population are vitamin D deficient at the time of diagnosis and treatment. Vitamin D deficient patients have an inferior event-free and overall survival compared to patients with vitamin D levels within the normal range. Vitamin D supplementation during treatment of DLBCL patients with vitamin D deficiency should be evaluated in a clinical trial setting. Disclosures: No relevant conflicts of interest to declare.

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Effect of Active Hepatitis C Infection in Relapse-Free Survival Among Patients with HIV‐Related Diffuse Large B‐Cell Lymphoma

Blood ◽

10.1182/blood-2019-129379 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4132-4132

Author(s):

Jesus D Gonzalez-Lugo ◽

Ana Acuna-Villaorduna ◽

Urvi A Shah ◽

Ellen W. Friedman

Keyword(s):

Clinical Outcomes ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Complete Response ◽

Hcv Infection ◽

Relapse Free Survival ◽

Hcv Treatment ◽

Free Survival ◽

Large B Cell Lymphoma ◽

Large B Cell

Introduction: Diffuse-large B cell lymphoma (DLBCL) is the most common lymphoma associated with Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV). During the past decades, the incidence of HIV-related lymphomas has declined; however, it still remains a major cause of morbidity and mortality in this population. Before highly effective antiretroviral therapy for HIV was introduced, individuals with HIV-related DLBCL had worse complete response and survival rates compared to their uninfected counterparts. Additionally, recent studies have shown that relapse rates are lower for DLBCL patients that achieve HCV sustained virological response (SVR). Nevertheless, outcomes in patients with active HCV infection among patients with HIV-related DLBCL have not been reported yet. This study is aimed to compare the clinical outcomes in HIV-related DLBCL among patients with and without active HCV infection. Methods: Patients with HIV infection and newly diagnosed DLBCL between 2005 and 2017 at Montefiore Medical Center/Albert Einstein College of Medicine were identified using the institutional software Clinical Looking Glass. Cases were grouped into concomitant HIV and HCV infection (HIV + HCV) or HIV alone (HIV) based on HCV antibody and viral load counts at DLBCL diagnosis. Patients with active hepatitis B infection were excluded. Data regarding demographics, laboratory parameters, HCV treatment, lymphoma treatment and clinical outcomes including complete response (CR), progression of disease (POD) and relapse were collected by manual chart review and compared among groups. SVR was defined as undetectable HCV RNA level 12 weeks after HCV treatment completion. Clinical outcomes were compared between patients with and without active HCV at the time of outcome evaluation. For this purpose, patients that achieved SVR for HCV were analyzed in the HIV group. Kaplan-Meier curves were plotted to compare 12-months relapse-free survival (RFS) among groups. Statistical analysis was performed using Stata 14.1. Results: A total of 63 patients were identified, of whom 45 (71.4%) had HIV alone (HIV) and 18 (28.6%) had concomitant active HCV and HIV infection (HIV + HCV). The median age was 49 years (IQ: 40-54), there were 39 (61.9%) males, 27 (42.9%) were Non-Hispanic Black and 27 (42.9%) were Hispanic. At DLBCL diagnosis, the majority of cases had advanced stages (stage 3: 15; 25% and stage 4: 40; 66.7%), the median CD4 count was 117 (IQ: 65-217) and 45 (72.6%) had AIDS. Baseline characteristics did not differ among groups. Of 63 patients, 53 (84.1%) were treated for DLBCL. Treatment regimens included DA-EPOCH (28; 50.9%), CHOP (22; 40%) and others (3; 9.1%). Rituximab was given to 33 cases (57.9%). Within the HIV + HCV group, only 3 (16.7%) patients received treatment for HCV; all of them were treated with ledipasvir/sofosbuvir and achieved SVR. In the full cohort, CR was achieved in 17 (32.1%) treated patients and 19 (35.9%) had POD. The CR rate was lower for patients with active HCV + HIV compared to HIV alone (7.1% vs. 41%, p=0.02) and there was no difference in POD among groups (28.6% vs. 38.5%, p=0.37). Patients with active HCV + HIV had a significantly lower 18-month RFS compared to those with HIV (62.9% vs. 87.4%, p=0.035). In a multivariate model adjusted for stage, AIDS and rituximab use; active HCV + HIV was a predictor for relapse (OR:6.36, 95% CI: 1.01 - 39.9, p=0.048). Conclusions: Despite available and effective treatment against HCV infection, only a minority of patients with DLBCL-related HIV received HCV treatment. Active HCV seems to play a role in the outcomes of patients treated for DLBCL and was found to be a predictor for relapse. Hence, HCV treatment should be considered for patients with HIV-related DLBCL. Disclosures Shah: Physicians' Education Resource: Honoraria. Friedman:Incyte pharmaceutical: Membership on an entity's Board of Directors or advisory committees, Research Funding.

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Favorable Results of Rituximab in Combination with CHOP in the Front-Line Treatment of Follicular Lymphoma Grade 3.

Blood ◽

10.1182/blood.v108.11.2770.2770 ◽

2006 ◽

Vol 108 (11) ◽

pp. 2770-2770

Author(s):

Luis Fayad ◽

Michael Overman ◽

Barbara Pro ◽

Peter McLaughlin ◽

Felipe Samaniego ◽

...

Keyword(s):

Follicular Lymphoma ◽

B Cell ◽

Response Rate ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Bulky Disease ◽

Large B Cell Lymphoma ◽

Grade 3 ◽

Large B Cell

Background: Follicular lymphoma grade 3 has a natural history that is more akin to that of diffuse large B-cell lymphoma. The addition of rituximab to standard CHOP has resulted in improved response and survival in diffuse large B-cell lymphoma. Information about outcomes in follicular lymphoma grade 3 is lacking. Methods: A single institution retrospective review of patients with follicular grade 3 lymphoma evaluated at the UTMDACC from 1999 to 2004. Patients were located from the UTMDACC lymphoma database. All patients were initially treated with R-CHOP. Results: Forty-five patients were identified: 51% male, 47% ≥60 years, and 87% follicular grade 3b. The LDH was elevated in 24%, ECOG performance status was >1 in 2%, and >1 site of extranodal involvement was present in 10%. Stage distribution was 11% stage I, 11% stage II, 42% stage III, and 36% stage IV, bulky disease (>7cm) was present in 11%, and B symptoms occurred in 13%. Beta-2 microglobulin was elevated in 57% with values >3 μg/dL in over 50%. IPI distribution was: 46% IPI Low, 38% LI, 11% IH, and 4% IPI High. Overall response rate was 100% with 96% complete responses. Relapse rate by IPI category was 24% for Low IPI, 18% for IPI LI, and 40% for IPI IH, and 100% for the two patients with High IPI. With median follow-up of 33 months, three year failure-free survival (FFS) is 73% (95% CI: 59 to 87%). One patient died (2%) with an overall survival (OS) at three years of 97% (95% CI: 93 to 100%). Conclusion: The addition of rituximab to CHOP provided a high response rate and excellent early survival in this group of mostly good prognosis patients. Relapses were still seen; longer follow-up is needed.

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Recurrence Patterns of Non-Mycosis Fungoides Cutaneous Lymphoma Following Various Treatment Modalities.

Blood ◽

10.1182/blood.v108.11.4676.4676 ◽

2006 ◽

Vol 108 (11) ◽

pp. 4676-4676

Author(s):

Michael E. Confer ◽

Jonathan D. Tward ◽

Sherrie L. Perkins ◽

Glen M. Bowen ◽

Robert J. Lee ◽

...

Keyword(s):

Overall Survival ◽

Radiation Therapy ◽

B Cell ◽

Initial Treatment ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Relapse Free Survival ◽

Free Survival ◽

Large B Cell Lymphoma ◽

Large B Cell

Abstract INTRODUCTION: Non-mycosis fungoides (MF) primary cutaneous lymphoma (PCL) is rare, and the more indolent forms seldom progress to fatal, systemic lymphoma. Nevertheless, frequent relapses are common. Although several therapies exist, no standard of care has been established for initial treatment. OBJECTIVES: To compare the role of radiotherapy to other initial treatment options and to evaluate clinicopathologic factors affecting overall, cause-specific, and relapse-free survival METHODS: Thirty-eight patients from 1985 to 2006 were retrospectively identified and reviewed with non-MF PCLs including: primary cutaneous anaplastic large cell lymphoma, subcutaneous panniculitis-like T-cell lymphoma, primary cutaneous marginal zone B-cell lymphoma, primary cutaneous follicle-center lymphoma, primary cutaneous diffuse large B-cell lymphoma, leg type, or primary cutaneous intravascular large B-cell lymphoma. Regression-free, cause-specific, and overall survival was estimated using the methods of Kaplan and Meier. Outcomes were compared with the log-rank test and Cox regression analysis. RESULTS: 38 patients were included in the analysis with a median follow-up time of 34.6 months (range 2 – 138 months). The distribution of initial treatment was: surgery - 29%, topical therapy - 16%, systemic therapy - 18%, and radiation - 63%. Three patients never received radiation. For the entire cohort, the 5-year overall (OS), cause-specific (CSS), and relapse free survival (RFS) was 86.2%, 88.9%, and 29.5% respectively. Subjects who received radiation therapy (n=24) as part of their initial treatment course had a significantly longer median time to first relapse of 57 months compared to 3.2 months for the 14 subjects who did not receive radiotherapy (log-rank p < 0.0001). Overall survival was significantly improved for subjects whose International Prognostic Index (IPI) score was 0–1 (n=25) versus those whose score was 2 or greater (n=13, p=0.05). Multivariate analysis for RFS revealed that the absence of radiation as part of initial treatment (Hazard Ratio (HR) = 22.2, 95% CI 2.1 – 238.5, p=0.01) and aggregate size less than 10cm (HR 0.04, 95% CI 0.0 – 0.3, p<0.01) significantly altered the risk of relapse. No relapses were observed within the radiation therapy treatment field in 31/35 (89%) subjects following their first course of radiation therapy. Of the 15/35 (43%) of patients that relapsed anywhere following radiation, only 2/15 (13%) relapsed in-field exclusively, 2/15 (13%) relapsed both in and out-of-field, and the remaining 11/15 (73%) relapsed exclusively outside the area treated. No patient relapsed within the treatment field of after 24 months. CONCLUSION: An initial course of radiation therapy significantly delays relapse compared to other therapies for non-MF PCL and provides excellent local control of plaques. Our findings also extend the IPI as prognostic for overall survival for this rare disease. Bulky lesions greater than 10cm in any one dimension are more strongly correlated with relapse.

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Extranodal Diffuse Large B Cell Lymphoma In The Rituximab Era and The Risk of Central Nervous System (CNS) Relapse. A Single Center Experience From 2008-2012

Blood ◽

10.1182/blood.v122.21.4330.4330 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4330-4330

Author(s):

Christina Tsao ◽

Kate Fisher ◽

Ji-Hyun Lee ◽

Julio C Chavez ◽

Samir Dalia ◽

...

Keyword(s):

Bone Marrow ◽

Cell Lymphoma ◽

Bone Marrow Involvement ◽

Progression Free Survival ◽

B Cell Lymphoma ◽

Free Survival ◽

Large B Cell Lymphoma ◽

Cns Relapse ◽

Musculoskeletal Involvement

Abstract Background Diffuse large b-cell lymphoma (DLBCL) with CNS relapse or progression has a poor prognosis. Prior studies noted certain factors which increased the risk of CNS relapse: bone marrow involvement, type as well as number (1+) of extra-nodal sites, age over 60, and increasing International Prognostic Index (IPI) score. However, these were prior to the advent of rituximab (R), which has been suggested to lower CNS relapse when used in combination with CHOP therapy. To our knowledge, no one has looked at the incidence of CNS relapse with regards to extranodal disease in the rituximab era. Methods Retrospective chart review of patients with DLBCL treated with multiagent induction therapy including rituximab from July‘08 to Jan’12 at Moffitt Cancer Center. Age, stage, IPI score, extra-nodal site, number of nodal sites, and use of intrathecal prophylaxis (IT), were evaluated for their impact on the risk of developing CNS relapse. For those who had complete response to initial therapy, time to progression(TTP) for CNS relapse was measured from completion date of first set of chemo cycles to date of CNS relapse (those who did not CNS relapse were censored at last follow up). TTP was censored at 6 years. Progression free survival(PFS) was measured from date of diagnosis to date of CNS or systemic relapse or death (those who were alive without relapse were censored at last follow up). Overall survival (OS) was measure from date of diagnosis to date of death. Stratified Kaplan Meier curves(with log rank p-values) and Cox PH models(with Wald p-values) were used to explore potential risk factors associated with relapse. Results Sixty-four patients with DLBCL who received induction therapy were evaluated: median age (range) = 65 (24-93) years; male =56%; IPI scores at diagnosis: 1 (43.8%), 2(21.9%), 3(15.6%); median length of follow up from time of diagnosis = 32 months. All the patients received a regimen containing rituximab, and 92% of patients received R-Chop as treatment. IT prophylaxis with methotrexate was used in 28% of the patients. Incidence of CNS relapse in our study population= 17.3% (n=9) The risk of CNS relapse varied depending on the extranodal site. Those with bone marrow and/or musculoskeletal involvement had an increased risk, with 78% of the CNS relapses occurring in patients with one or both of these sites of involvement. The hazard ratio (HR) for CNS relapse for patients with bone marrow and musculoskeletal involvement was 2.53 and 2.74, respectively (p=0.20 and p=0.13). Other extranodal sites of disease such as visceral organs, genital urinary tract, nasopharynx, or skin did not seem to significantly contribute to the risk of CNS relapse. Patients with bone marrow involvement also had an inferior overall survival (HR=3.05, Wald p=0.02) (see figure 1). Though not statistically significant (log rank p=0.126), those receiving IT methotrexate prophylaxis appear to have longer PFS than those who did not, with 83% alive without relapse at 6 years compared to 43% (see figure 2). Conclusions Despite the addition of rituximab to multiagent chemotherapy, those with bone marrow and musculoskeletal involvement still had a significantly higher risk of CNS relapse. There is a trend which suggests intrathecal prophylaxis with methotrexate can improve progression free survival and is still possibly beneficial in high risk DLBCL patients even in the rituximab era. Larger prospective studies are needed to determine the true benefit of prophylactic IT therapy in this population. Disclosures: No relevant conflicts of interest to declare.

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The use of checkpoint inhibitors in children with non-Hodgkin lymphomas

Pediatric Hematology/Oncology and Immunopathology ◽

10.24287/1726-1708-2020-19-2-112-120 ◽

2020 ◽

Vol 19 (2) ◽

pp. 112-120

Author(s):

A. V. Kozlov ◽

I. V. Kazantsev ◽

T. V. Yukhta ◽

P. S. Tolkunova ◽

A. G. Gevorgyan ◽

...

Keyword(s):

B Cell ◽

Cell Lymphoma ◽

Checkpoint Inhibitors ◽

B Cell Lymphoma ◽

Complete Response ◽

Median Number ◽

Hematopoietic Stem ◽

Large B Cell Lymphoma ◽

Large B Cell

The majority of children with NHL can be cured with first-line therapy but 10–25% of affected patients develop relapsed or refractory disease (R-R). The prognosis in these cases is unfavorable, no matter what form of modern treatment is adopted. New approaches to the treatment of this small, yet important, group of patients need to be introduced, including, first and foremost, targeted therapy and immunotherapy. As is known, PD-L1 is frequently expressed in non-Hodgkin lymphomas (NHL), which means that the use of checkpoint inhibitors (CPI) is theoretically justified. Objectives: to analyze the results of treatment with checkpoint inhibitors Nivolumab and Pembrolizumab in children with R-R NHL. The study was approved by the Independent Ethics Committee of the I.P. Pavlov First Saint-Petersburg State Medical University. We used CPIs in 8 children with R-R NHL undergoing treatment at the R.M. Gorbacheva Research Institute for Pediatric Oncology, Hematology and Transplantation. The median age was 12 (2–17) years. The distribution of the patients by diagnosis was as follows: primary mediastinal large B-cell lymphoma (PMBCL, n = 3), peripheral T-cell lymphoma (PTCL, n = 2), diffuse large B-cell lymphoma (n = 1), lymphoblastic lymphoma (n = 2). The median number of prior lines of therapy was 3 (1–5), and all patients had received at least 1 line of standard treatment. Refractory NHL was observed in 5 cases, and 3 patients had had multiple relapses (≥ 3). All patients had progression of their primary disease at the time of prescription of the CPI therapy. Nivolumab was administered at a dose of either 1 mg/kg (n = 4) or 3 mg/kg (n = 3) every 2 weeks, Pembrolizumab - at a dose of 2 mg/kg once every 3 weeks (n = 1). The median number of CPI doses received by the patients was 5.5 (2–12). In 5 patients, CPIs were administered as monotherapy, in 3 – in combination with cytostatic agents: FLAG, Gemcitabine and intrathecal triples (n = 1), Brentuximab vedotin (n = 1) and Bendamustine (n = 1). The efficacy of the treatment was evaluated in accordance with the LYRIC criteria. Once remission was achieved, we used hematopoietic stem cell transplantation and/or radiotherapy for consolidation. Response to the CPI therapy was observed in 4 out of 8 patients (complete response – in 2 patients). Interestingly, only patients with PMBCL and PTCL responded to the treatment. At the median follow-up of 368 (36–879) days, 5 patients were alive, with three of them remaining in long-term remission. During the follow-up period, there was only 1 clinically significant complication (cytopenia) that resolved after treatment with glucocorticosteroids. Finally, we would like to point out that this paper is one of the first reports on the successful use of CPIs in children with R-R NHL. PMBCL and PTCL turned out to be responsive to the treatment. This therapy can be used to achieve remission or possibly even cure in children whose only option would be palliative care if they were treated with standard approaches.

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A multi-institutional analysis of diffuse large B-cell lymphoma (DLBCL) treated with consolidative radiotherapy and the impact of cell-of-origin on outcomes

Radiology and Oncology ◽

10.2478/raon-2019-0045 ◽

2019 ◽

Vol 53 (4) ◽

pp. 473-479 ◽

Cited By ~ 1

Author(s):

Chrishanthi Rajasooriyar ◽

Jeremy Tey ◽

Lea Choung Wong ◽

Michelle Poon ◽

Rao Nandini ◽

...

Keyword(s):

B Cell ◽

Cell Lymphoma ◽

Disease Free Survival ◽

B Cell Lymphoma ◽

Complete Response ◽

Cell Of Origin ◽

Bulky Disease ◽

Large B Cell Lymphoma ◽

The Impact ◽

Large B Cell

Abstract Background Patients with diffuse large B-cell lymphoma (DLBCL) with bulky disease and/or those who fail to achieve complete response benefit from the addition of radiotherapy (RT). We aim to review the outcome, as well as determine the impact of cell-of-origin, on patients undergoing consolidative RT. Patients and methods Patients with DLBCL treated with radical intent consolidative RT were included. Clinical, pathological and treatment characteristics were extracted from electronic medical records. Survival outcomes and factors that predict for disease-free survival (DFS) were analysed. Results Seventy-four patients were included in this analysis. The median follow up was 3 years (0.7–16 years). Fifty-eight percent of patients had stage I–II disease, and 61% received at least 6 cycles of chemotherapy. Cell-of-origin was discernible in 60% of patients, and approximately half were classified as Germinal centre origin. The 5-year overall survival (OS) of this group was excellent at 92% (median survival not reached). The 5-year DFS was 73% (95% CI 57–83%). Seven percent (n = 5) of patients experienced local recurrence at a median time of 6 months. Failure to achieve complete response post RT and/or initial bulky disease are significant predictors of inferior DFS. There was no association between cell-of-origin and DFS or OS. Conclusions The outcome of patients who received radiotherapy as consolidation is excellent. Patients who fail to achieve complete response after radiotherapy had poorer outcomes. Despite using radiotherapy, presence of bulky disease remains a significant predictor of disease recurrence. We did not find any association of poorer outcomes, with regards to cell-of-origin, in the use of consolidative RT.

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