Outcome of Adolescent & Young Adult (AYA) Patients with Diffuse Large B-Cell Lymphoma (DLBCL)

Abstract Abstract 1568 Introduction Non-Hodgkin lymphoma (NHL) represents 60% of lymphoma diagnoses in children, and NHL subtypes change considerably from childhood to adulthood.[1] Recent studies have implicated age-associated biological differences in certain NHL subtypes.[2] AYAs with cancer fall between pediatric and adult patients clinically and potentially biologically. Although environmental stressors and the psychosocial transition of adolescence likely impacts these outcomes, age-related biological differences need to be better understood. The majority of pediatric NHLs are high-grade tumors, whereas low- and intermediate-grade tumors are more common among adults.[1] Recent studies have found that young adults with NHL have poorer survival compared to children.[2] Although the incidence of AYA lymphoma has increased over the past 20 years, survival has not significantly improved, demanding a better understanding of the epidemiology and biology of lymphoma among this patient population.[3] Methods Cases were identified using the Nebraska Lymphoma Study Group database and chart review. All patients with DLBCL from 1983–2010 were identified (n = 1328), and 36 (2.7%) cases are included in this study of AYA DLBCL (age 13–30 years). The Kaplan-Meier method was used to estimate overall survival (OS) and event-free survival (EFS) distributions, and the log-rank test was used to compare survival distributions between groups. OS is defined as the time from the beginning of therapy to death or last follow-up. EFS is defined as the time from the beginning of therapy to progression, death, or last follow-up. P-values less than 0.05 are considered to be statistically significant. SAS software V 9.2 (SAS Institute Inc., Cary, NC) was used for all data analysis. The study was approved by the Institutional Review Board. Results The median age of the 36 AYA DLBCL patients was 24.2 years (range, 14.5–29.8) with a female to male ratio of 1.8:1, and 53% were primary mediastinal B-cell lymphoma. Patient characteristics are shown in table 1. Of the 36 patients, 18 have died and 18 are alive at last follow-up. Fifteen deaths were due to lymphoma, 1 treatment related, 1 unrelated to disease, and 1 of unknown cause. The 5-year EFS is 52% (95% CI 34–67%, figure 1) and OS is 58% (95% CI 49–72%). The median follow-up of patients alive at last follow-up is 8.8 years (range, 1.8 – 29). OS was not affected by gender (p=0.32), stage (p=0.43), LDH (p=0.11), B symptoms (p=0.98), or size of the largest mass at diagnosis (0.93). Nearly all patients (97%) were treated on adult chemotherapy protocols. Discussion This study presents data on 36 AYA patients with DLBCL. The 5-year EFS was 52% and OS was 58%. Pediatric patients report a 5-year EFS of 87–96% [2, 4] compared to adults which have a 5-year EFS of 44–80%.[4] In contrast to other reports, in this study, gender, elevated LDH, and advanced stage (III-IV) did not impact EFS or OS, although the comparisons may be under-powered due to the small sample size. Although pediatric patients have better outcomes compared to adults, AYA patients have worse EFS than both pediatric and adult DLBCL patients, demanding further understanding of the biology of AYA DLBCL and improved treatment strategies. Disclosures: No relevant conflicts of interest to declare.

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Laterality and Survival Outcomes in Patients with Primary Testicular Diffuse Large B Cell Lymphoma

Blood ◽

10.1182/blood-2019-129952 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2903-2903

Author(s):

Yi Miao ◽

Lei Fan ◽

Wei Xu ◽

Jianyong Li

Keyword(s):

B Cell ◽

Survival Data ◽

Conflicts Of Interest ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Rank Test ◽

P Value ◽

Large B Cell Lymphoma ◽

Large B Cell

Introduction: Patients with diffuse large B cell lymphoma (DLBCL) arising from the testis have a relatively poor outcome. Age, stage and use of radiation and surgery are important prognostic factors in patients with primary testicular DLBCL. Additionally, the study by Gundrum et al suggested that laterality was also an important predictor of outcomes in patients with primary testicular DLBCL, with left side involvement being associated poorer prognosis. However, most patients included in the study by Gundrum et al were diagnosed in the pre-rituximab era, therefore, the role of laterality in the prognostification of patients with primary testicular DLBCL remains to be explored. In this study, the Surveillance, Epidemiology, and End Results (SEER) database was used to evaluate the prognostic roles of laterality in patients with primary testicular DLBCL. Methods: Data from the SEER 18 Registries were used to conduct this study. Cases with newly-diagnosed testicular (International Classification of Diseases for Oncology, 3rd Edition [ICDO-3] codes 9823, sites: C62.0-C63.2) in the time period between 1973 and 2015 were included. Exclusion criteria included history of cancer, unknown laterality, unknown survival data and unknown cause of death. For each case we included age at the time of diagnosis, laterality (left, right, bilateral), SEER cause-specific death classification, survival months and vital status. Overall survival (OS) was defined as time from diagnosis to death or last follow-up and cancer-specific survival (CSS) was calculated as time from diagnosis to death from DLBCL or last follow-up. Survival curves were plotted by the Kaplan-Meier method and the log-rank test was used for comparison. P value was 2-sided and P<0.05 was considered to be statistically significant. All analyses were conducted using Graphpad Prism 6. Results: A total of 1213 patients were included in this analysis. The median follow-up was 43 months (interquartile range[IQR]: 13-90 months). Of these patients, 372 patients were diagnosed from 1973-2000 (pre-rituximab era) and 841 patients were diagnosed from 2001-2015 (rituximab era). We found that patients with bilateral testis involvement had a significantly decreased CSS (median CSS: 53 vs. 142 months, P=0.0035) and OS (median OS: 32 vs. 77 months, P=0.0008) compared with those with unilateral involvement. Patients with left-side involvement had a similar CSS (median CSS: 136 vs. 153 months, P=0.2997) and OS (median OS: 76 vs. 80 months, P=0.7360) compared to those with right-side involvement. For patients with left-side involvement, patients diagnosed in the rituximab era had a significantly longer CSS(hazards ratio[HR]: 0.4140, 95% confidence interval[CI]: 0.3065 to 0.5593, P<0.0001) (Figure 1A)and OS (HR: 0.5522, 95% CI: 0.3926 to 0.6340, P<0.0001 ) (Figure 1B) than those diagnosed in the pre-rituximab era. For patients with right-side involvement, patients diagnosed in the rituximab era had a significantly longer CSS (HR: 0.7146, 95% CI: 0.5218 to 0.9029, P=0.0057) (Figure 1A)and OS (HR: 0.7116, 95% CI: 0.5407 to 0.8311, P=0.0011) (Figure 1B)than those diagnosed in the pre-rituximab era. The different HRs suggested patients with left-side primary testicular DLBCL benefited more from the introduction of rituximab. Additionally, the improvement in median OS from the pre-rituximab era to the rituximab era was 68 months for patients with left-side involvement but only 35 months for patients with right-side involvement. Conclusion: our study demonstrated that laterality was not a prognostic factor for patients with primary testicular DLBCL. And the improvement in the prognosis from pre-rituximab era to rituximab era was more remarkable in primary testicular DLBCL patients with left-side involvement than those with right-side involvement. These data suggest primary testicular DLBCL from different sides had different responses to therapy and may have different biological characteristics. Figure 1 Disclosures No relevant conflicts of interest to declare.

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Concurrent Follicular Lymphoma At Diagnosis Has a Negative Impact On The Outcome Of Patients With Diffuse Large B Cell Lymphoma

Blood ◽

10.1182/blood.v122.21.4260.4260 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4260-4260 ◽

Cited By ~ 2

Author(s):

David Wrench ◽

Hasan Rizvi ◽

Andrew Wilson ◽

Ciaran O'Riain ◽

Andrew Clear ◽

...

Keyword(s):

Follicular Lymphoma ◽

B Cell ◽

Conflicts Of Interest ◽

Cell Lymphoma ◽

Negative Impact ◽

Tissue Sample ◽

B Cell Lymphoma ◽

Large B Cell Lymphoma ◽

Large B Cell

Abstract In contrast to either de novo diffuse large B cell lymphoma (dnDLBCL) or follicular lymphoma (FL) that transforms to DLBCL, the clinical course of DLBCL and FL presenting simultaneously (DLBCL/FL) is not well characterised. From 1 October 1975 to 31 December 2010, 819 patients were diagnosed with DLBCL at St Bartholomew’s Hospital. Twenty-seven patients with bone marrow (BM) involvement were excluded because of histologies other than FL or DLBCL in the BM (n=2) or unavailable BM samples (n=25). The remaining patients comprised the study population (n=792) which consisted of 45 histologically confirmed DLBCL/FL and 747 dnDLBCL. A pathological review was performed of all DLBCL/FL and all the positive BM samples. Remission duration (RD), progression-free survival (PFS), overall survival (OS) and lymphoma-specific survival (LSS) were compared in DLBCL/FL and dnDLBCL. DLBCL/FL comprised composite (both histologies in the same tissue sample; n=24) and discordant (both histologies in separate tissue samples; n=21) lymphoma. The majority (n=18, 75%) of composite DLBCL/FL were diagnosed on lymph node (LN) sampling with the remainder identified in tonsil (n=3) with single cases in testis, salivary gland and BM. Discordant DLBCL/FL, presented as DLBCL and FL involving LN and BM respectively in 16 cases (76%). Other combinations included DLBCL and FL in separate LNs (n=2) and one each of kidney + BM, mesentery + LN, bone biopsy + BM. At presentation, DLBCL/FL had more advanced stage (p<0.01), higher IPI (p=0.02) and lower Hb (p=0.02) than dnDLBCL in keeping with BM involvement rates of 19/45 (42%) and 32/747 (4%), respectively. Most DLBCL/FL (n=42; 93%) received anthracycline based combination chemotherapy (a single case received HD-MTX and 2 cases palliative / no treatment both of whom died within 3.5 months) and, since 2003, addition of rituximab (24% of cases) to CHOP (n=10) or CODOX-M/IVAC (n=1); with similar rates of anthracycline (82%) and rituximab (29%) use in dnDLBCL. The 44 documented responses in DLCBL/FL included complete response (CR, n=26; 59% similar to 66% in 696 patients with dnDLBCL and assessable responses), partial response (n=7) and stable disease/progression (n=11) with a shorter RD for DLBCL/FL (median 8.7 yrs) compared to dnDLBCL (median not reached), although this was not statistically different (p=0.09). PFS was significantly shorter for DLBCL/FL in comparison with dnDLBCL (2.0 versus 4.6 yrs, respectively; p=0.02) and DLBCL/FL not achieving CR had inferior OS (0.4 yrs) than those achieving CR (11.5 yrs; p<0.01). Relapse after CR occurred in 12/26 (46%) patients with DLBCL/FL and in 142/456 (31%; p=0.13) of those with dnDLBCL; 83% and 87% relapsed cases have died, respectively. With a median follow-up of 10 yrs, 71% patients with DLBCL/FL have died as compared to 65% patients with dnDLBCL, and no differences in median OS were observed (4.0 yrs for DLCBL/FL versus 5.5 yrs for dnDLBCL; p=0.28). Death was most commonly due to lymphoma, the rate being similar in patients with DLBCL/FL (56%) and dnDLBCL (52%). However, LSS was shorter for DLBCL/FL (6.3 yrs) than dnDLBCL (13.8 yrs; p<0.01) and, with the long follow-up, we found no differences in OS between DLBCL with concordant (DLBCL, n=32) or discordant (FL, n=18) BM involvement (p=0.38). This study, to the authors’ knowledge the largest series of concurrent FL and DLBCL, confirms the relative frequency of DLBCL/FL to DLBCL (45:747, 6%) and demonstrates that the simultaneous presence of FL negatively influences the outcome of patients with DLBCL, by shortening PFS and LSS. This data emphasizes the importance of thorough staging at diagnosis, including BM biopsies, and highlights the need for better management of this population, which has a worse prognosis than dnDLBCL and is frequently excluded from clinical trials. Disclosures: No relevant conflicts of interest to declare.

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Clinical Pharmacokinetic (PK) and Safety (Immunogenicity) of Rituximab Biosimilar RTXM83 in Combination with Chemotherapy CHOP in Patients with Diffuse Large B-Cell Lymphoma (DLBCL)

Blood ◽

10.1182/blood.v124.21.5472.5472 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5472-5472 ◽

Cited By ~ 5

Author(s):

Amalia Florez ◽

Thiago Di Matteo ◽

Gloria Fresnillo ◽

Consuelo Tudela ◽

Mauricio Seigelchifer ◽

...

Keyword(s):

B Cell ◽

Conflicts Of Interest ◽

Cell Lymphoma ◽

Analytical Data ◽

B Cell Lymphoma ◽

Assay Sensitivity ◽

Large B Cell Lymphoma ◽

Large B Cell ◽

The Eu

Abstract Background: RTXM83 is a rituximab biosimilar candidate manufactured by MAbxience Company. Full spectrum of physicochemical and preclinical studies showed biosimilarity of RTXM83 and originator drug MabThera®/Rituxan® marketed by Roche. MabThera®/Rituxan® product is approved to treat Non-Hodgkin´s Lymphoma, chronic lymphocytic leukemia and rheumatoid arthritis in the EU and US, plus it is approved to treat Diffuse Large B-cell lymphoma (DLBCL) in the EU. Rituximab is also used for other types of lymphoma (e.g. Mantle cell lymphoma) in certain parts of the word. Objective: To demonstrate comparable pharmacokinetics (PK) and safety profile (immunogenicity) to MabThera®, a clinical PK/immunogenicity analysis was designed to compare RTXM83 and MabThera® when administered with CHOP to patients with DLBCL. Methods: Analysis of an interim PK/Safety report from randomized and blinded study, where 24 patients with newly diagnosed DLBCL treated with R-CHOP as part of a multi-center study undertaken to assess the PK and immunogenicity. R-CHOP (rituximab-375mg/m2; cyclophopsphamide-750mg/m2; adriamycin-50mg/m2; vincristine-1.4mg/m2 on day 1 and prednisolone-60mg/m2 on days 1 to 5) was given every 3 weeks for a total of 6 cycles. The PK analysis were conducted on quality control (QC) checked analytical data for Cycle 1 and Cycle 6 using nominal blood sampling times. PK parameters were determined from the serum Rituximab concentration-time profiles obtained following administration of the first (Cycle 1) and last intravenous infusion of study medication (Cycle 6) using non-compartmental procedures in Phoenix WinNonlin (Version 6.2.1). The immunogenicity assessments were based on a specific and validated method for systematic evaluation of an unwanted immune response against RTXM83 and MabThera®. In fact, a confirmatory assay and specific cut point was established as current described recommendations in white papers and guidance documents. This part assures the assay sensitivity and a “characterization step” in the study sample analysis. A screening assay that picks up 5% positives that are subsequently shown to be due to non-specific binding in a confirmatory (immunodepletion) assay provides assurance that true low positives can be detected. Finally, the clinical immunogenicity measurements were performed on Cycle 5, Cycle 6 and follow-up patient samples. Results: Following the end of infusion of 375 mg/m2 q3w RTXM83 or MabThera® (Rituximab) (3 hours infusion) administered in combination with CHOP in Cycle 1 and Cycle 6, serum concentrations of Rituximab declined steadily in a generally bi-phasic manner. The arithmetic mean ±SD of PK parameters (T1/2(hrs); Cmax (ug/ml); Cmin (ug/ml); AUC0-∞ (ug*hrs/ml) of Rituximab during cycle 1, cycle 6 and follow-up patients were determined. All these data are comparable with values previously reported for rituximab in other conditions. No anti-drug antibody case was reported, so RTXM83 and MabThera® displaying null or undetectable immunogenicity. Conclusions: The data indicate that therapeutic levels of rituximab (RTXM83/Mabthera®) were observed across studied cycles. All data are comparable with values previously reported for rituximab. Therefore, PK profile and immunogenicity profile of RTXM83 is comparable with Mabthera® in treating DLBCL. Disclosures No relevant conflicts of interest to declare.

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An Escalated Dose of Bortezomib Plus Second Line Chemotherapy for the Treatment of Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma,

Blood ◽

10.1182/blood.v118.21.3714.3714 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3714-3714

Author(s):

Yongqian Jia ◽

Bing Xiang ◽

Xiaodong Wang ◽

Jianjun Li ◽

Chuan He ◽

...

Keyword(s):

B Cell ◽

Conflicts Of Interest ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Fungus Infection ◽

Large B Cell Lymphoma ◽

One Year ◽

The One ◽

Large B Cell

Abstract Abstract 3714 Background: The non-GCB subtype of diffuse large B-cell lymphoma(DLBCL) has inferior response to rituximab based chemothrapy. Recent reports show a constitutional expression of NF-κB pathway in non-GCB subtype of DLBCL. Bortezomib, as proteasome inhibitor, has been shown a promising new agent for the treatment of DLBCL. As how the efficacy, doses and protocol of Bortezomib need to be clarified. Objective: This trial is a pilot multicenter clinical study to evaluate the efficacy and safety of an escalated dose of bortezomib based chemotherapy for the treatment of patients with relapsed or refractory non-GCB subtype of DLBCL. Patients and Materials: A total 24 pts with DLBCL were enrolled in 4 different medical centers. According to Hans' Tissue Microarray (TMA) Classification, 23 pts were diagnosed as non-GCB subtype, and 1 patient have not done the test. 16 pts had relapsed or refractory disease, while 8 pts had fail response to the first line treatment. All the patients had received Rituximab based chemotherapy previously. There were 16 male and 8 female. The patient age ranged from 19 to 73, of which the median age was 55. Methods: All patients were given bortezomib 2.0mg/m2, day 1, I.V. (intravenous injection 12 hours before chemotherapy), 5 pts were given additional dose of 0.7 mg/m2, I.V., at day 8. The combination protocols include: Bortezomib(V)+ICE(G) 13 pts; Bortezomib(V)+HyperCVAD 7 pts; Bortezomib(V)+EPOCH 3 pts; Bortezomib(V)+DHAP 1 pts. The patients were given 1 to 5.courses differently. Results: The follow-up time were 2 to18 months, with a median time of 8 months. Of 24 pts, 21 evaluable pts received more than 2 courses of therapy: 7 pts achieved complete remission (CR 33.3%), 9 pts achieved partial remission (PR 42.8%), 5 pts had no response (NR 23.8%), The overall response rate (ORR) was 76.1%. Of 16 responsive pts, the PFS were 2 to 18 months; the average PFS was 7.6 months and median PFS was 7.5 months. Up to now, 13 pts were still alive, and 7 pts were dead, and 1 pts lost follow-up. Of 7 death, 5 were caused by disease progression with 4 pts of central nervous infiltrates, 2 were caused by severe infections. The one year overall survival rate (OS) was 65%. Of all the 24 pts, 10 pts had 3 to 4 grade of myelosuppression; 1 case with severe pulmonary infection;1 case with septicemia; 1 case with skin and soft tissue infection; 1 case with fungus infection; 3 cases with herpes zoster infection; 2 cases with skin rashes; 2 cases with hypotension, 1 case with hepatic dysfunction; 1 case with neuralgia. Conclusion: Our study showed that the escalated dose of bortezomib based chemotherapy had promising response for the treatment of relapsed or refractory non-GCB originated DLBCL. Bortezomib at a single dose of 2.0mg/m2 was safe and tolerable. No acute toxicity or vital adverse events were observed. The relapse of disease in central nervous system as well as infections were relatively common and might need further study. Disclosures: No relevant conflicts of interest to declare.

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B Cell Lymphoma, Unclassifiable: Survival Advantage for Aggressive Therapy

Blood ◽

10.1182/blood.v118.21.2689.2689 ◽

2011 ◽

Vol 118 (21) ◽

pp. 2689-2689

Author(s):

Erin Cobain ◽

Tahamtan Ahmadi ◽

Marc Hoffmann ◽

Alison W. Loren ◽

Noelle V. Frey ◽

...

Keyword(s):

Disease Control ◽

B Cell ◽

Burkitt Lymphoma ◽

Conflicts Of Interest ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Data Set ◽

Hiv Test

Abstract Abstract 2689 Background: Burkitt lymphoma (BL) and B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma (BLL) are mature B-cell non-Hodgkin lymphomas with an aggressive clinical course. Whereas the advent of short, intensive, multi-agent chemoimmunotherapy regimens has significantly improved the outcomes for BL patients (pts), questions remain regarding the optimal therapy for BLL. Patients and Methods: We analyzed 25 patients (pts), aged 20 to 73 (median: 51 years), treated at the University of Pennsylvania for either BL or BLL from 2005 to 2010. All pts had c- myc+ lymphoma, with a Ki-67>98% and a negative HIV test. In order to be classified as BLL, expression of bcl-6 was required. Bcl-2 expression was noticed in 7/14 (50%) of BLL cases. All patients had Stage III/IV disease. All but two pts had high-risk disease by IPI. All 10 pts with BL were treated with the R-HyperCVAD regimen. Of the 14 pts with BLL, 7 where treated with R-HyperCVAD and 7 with R-CHOP (+ intrathecal prophylaxis in five out of seven pts). No differences in IPI, PS or co-morbidities were noted between the three groups. Notably, patients treated with R-CHOP were slightly younger with median of 52 years vs. median age of 62 years for those with BLL, treated with R-HyperCVAD. Results: Overall response rate (ORR) to R-HyperCVAD in BL was 70%, with two treatment-related deaths. At median follow up of 24 months, progression-free survival (PFS) was 72% (95% CI: 36–90%). ORR in BLL treated with R-HyperCVAD was 86% with one treatment-related death vs.57% when treated with R-CHOP, with two treatment-related deaths. At median follow up of 9 months for both groups, PFS for BLL treated with R-HyperCVAD was 54% (95% CI: 14–83%), whereas only one pt treated with R-CHOP was free of disease after 9 months with a median PFS of 8 months and median overall survival (OS) of 9 months. Within our data set, only one of the six pts with primary refractory disease and one of four relapses responded to salvage therapy. None of the BL/BLL pts treated with R-HyperCVAD, who achieved a CR, relapsed. Four of the seven relapses after R-CHOP presented with CNS involvement. Conclusion: Our data suggest that R-HyperCVAD allows for long-term disease control in both BL and BLL, with a somewhat lower PFS in BLL. In contrast, R-CHOP appears to be inferior with no long-term disease control in BLL. Disclosures: No relevant conflicts of interest to declare.

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Intensive Chemotherapy of 107 Primary Mediastinal B-Cell Lymphoma Patients. Single Center Experience

Blood ◽

10.1182/blood.v126.23.5494.5494 ◽

2015 ◽

Vol 126 (23) ◽

pp. 5494-5494 ◽

Cited By ~ 1

Author(s):

Jana Konstantinovna Mangasarova ◽

Sergey Kirillovich Kravchenko ◽

Aminat Umaraskhabovna Magomedova ◽

Anna Misyurina ◽

Elena Baryakh ◽

...

Keyword(s):

B Cell ◽

Conflicts Of Interest ◽

Cell Lymphoma ◽

Conditioning Regimen ◽

B Cell Lymphoma ◽

High Dose ◽

Single Center Experience ◽

Mediastinal Disease ◽

Ann Arbor

Abstract Introduction. Primary mediastinal B-cell lymphoma (PMBCL) amounts from 0,9 to 4% of Non-Hodgkin Lymphomas. Predominantly suffer young women. All relapses in PMBCL occur as early events. Taking into account unfavorable prognosis in case of relapse or progression of PMBCL (2-year overall survival (OS) is about 15% [Kurvilla J., 2008]), it's necessary to achieve a complete remission (CR) in first line treatment. Aim. To compare an efficacy of R-DA-EPOCH followed by R-DHAP and autologous peripheral blood stem cell transplantation (autoSCT) with BEAM conditioning regimen with modified (m) NHL-BFM-90 chemotherapy protocol in pts with partial remission (PR) of PMBCL. Patients and Methods. In 107 pts (34 males, 73 females) diagnosis of PMBCL was established according to WHO criteria. All pts had stage II of disease according to Ann Arbor classification. 30 pts received R-DA-EPOCH, 77 pts - m-NHL-BFM-90 ± R. Median age of pts in R-DA-EPOCH group was 28 years old (from 20 to 67 years old); in m-NHL-BFM-90 ± R-group - 77 years old. Increased LDH concentration was revealed in 24 from 30 (80%) pts in R-DA-EPOCH group and in 75/77 (97%) pts from m-NHL-BFM-90 ± R group. Bulky mediastinal disease was in 30/30 (100%) pts in R-DA-EPOCH group and in 59/77 (76%) - m-NHL-BFM-90 ± R group. In case of CR after 6 courses according to computer tomography and PET scanning treatment was completed. In case of PR pts underwent 2 R-DHAP courses with autoSCT (BEAM conditioning regimen). All pts from m-NHL-BFM-90 ± R group independently from PET-results stopped treatment. All cases of treatment failure occurred till one year of observation. Kaplan-Meier method was used to calculate OS and relapse-free survival (RFS). OS was defined as time from diagnosis to death from any reason; RFS was defined as time from diagnosis until relapse or death from any cause. Results: After 6 R-DA-EPOCH therapy CR was achieved in 24/30 (80%) pts, 6/30 (20%) pts had PR and underwent 2 R-DHAP courses followed by auto-SCT (BEAM). 2- RFS and OS was 100%. Median follow up was 16 months. In m-NHL-BFM-90 ± R group 10-year RFS and OS were 85% and 92%, respectively. Median follow up was 53 months. Conclusion: High dose pulsed m-NHL-BFM-90-chemotherapy as well as R-DA-EPOCH allows getting high efficacy of primary mediastinal B-cell lymphoma therapy. Although future analysis will show more distant results of R-DA-EPOCH chemotherapy. Disclosures No relevant conflicts of interest to declare.

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Benefit of Consolidative Radiotherapy in Patients with Limited Stage Diffuse Large B-Cell Lymphoma in the Rituximab Era

Blood ◽

10.1182/blood.v128.22.4210.4210 ◽

2016 ◽

Vol 128 (22) ◽

pp. 4210-4210

Author(s):

Nobuhiko Nakamura ◽

Yoshikazu Ikoma ◽

Yuhei Shibata ◽

Takuro Matsumoto ◽

Soranobu Ninomiya ◽

...

Keyword(s):

B Cell ◽

Conflicts Of Interest ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Stage I ◽

Limited Stage ◽

Large B Cell Lymphoma ◽

Consolidative Radiotherapy ◽

Large B Cell

Abstract Background: Diffuse large B-cell lymphoma (DLBCL) is an aggressive type of non-Hodgkin lymphoma and the most common lymphoid neoplasm in adults. In the pre rituximab era, the standard therapy for patients with limited stage DLBCL had been three cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) followed by involved-field radiotherapy (IFRT). The addition of rituximab has revolutionized the treatment of DLBCL. Rituximab combined with CHOP (R-CHOP) has been established as the standard treatment for patients with DLBCL. However, the role of consolidative radiotherapy (RT) in the treatment of limited stage DLBCL in the rituximab era is controversial. Patients and Methods: We retrospectively analyzed 108 patients with limited stage DLBCL who received R-CHOP or R-THP-COP (rituximab plus, cyclophosphamide, pirarubicin, vincristine and prednisone) regimen between June 2004 and August 2015. We compared overall survival (OS) and progression-free survival (PFS) according to the treatment. OS was calculated from the date of initiation of chemotherapy to the date of the last follow-up or death. PFS was calculated from the date of initiation of chemotherapy to the date of progression disease, death, or last contact, whichever occurred first. Survival was estimated from Kaplan-Meier curves and compared using the log-rank test. P < 0.05 was considered statistically significant. Weighted Cox proportional hazards regression modeling with the inverse probability weighted (IPW) estimators method adjusting to propensity for RT was used to account for differences in baseline characteristics. Results: Median age at diagnosis was 66 years (19-88 years), with 61 males and 47 females. Forty-three patients (40%) had stage I, and 65 patients (60%) received consolidative RT after chemotherapy. Patients who received consolidative RT were significantly younger (65 vs 72, P < 0.01) and were more likely to have stage I disease (51% vs 23%, P < 0.01). The median number of chemotherapy cycles was 4 (range 3-8) in patients who received RT, and 6 (range 3-8) in patients who did not. Median follow-up was 4.3 years (0.3-10.9 years), and the 5-year OS (92% vs 63%, P < 0.01) and PFS (87% vs 65%, P < 0.01) were significantly higher for patients who received RT than those who did not. Using IPW adjustment, RT remained predictive of OS (HR 0.30, CI 0.13-0.72, P < 0.01) and PFS (HR 0.47, CI 0.22-0.99, P < 0.05). Conclusion: Our results suggest that consolidative RT improves OS and PFS in patients with limited stage DLBCL in the rituximab era. Although consolidative RT seems to be gradually phased out by chemotherapy alone, it is still an important treatment strategy. Disclosures No relevant conflicts of interest to declare.

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Frontline Therapy of Nodular Lymphocyte Predominant Hodgkin Lymphoma with Rituximab: The Stanford University Experience

Blood ◽

10.1182/blood.v118.21.2686.2686 ◽

2011 ◽

Vol 118 (21) ◽

pp. 2686-2686 ◽

Cited By ~ 2

Author(s):

Ranjana H. Advani ◽

Sandra J. Horning ◽

Richard T. Hoppe ◽

Sarah Daadi ◽

John Allen ◽

...

Keyword(s):

B Cell ◽

Hodgkin Lymphoma ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Rank Test ◽

Newly Diagnosed ◽

Log Rank Test ◽

Anti Cd20 ◽

Aggressive B Cell Lymphoma

Abstract Abstract 2686 Background: Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare subtype of HL (∼5%). This unique clinical entity is characterized by an indolent clinical course and unlike classical HL late relapses may occur. Standard treatment depends on stage and includes radiation therapy (RT) and/or chemotherapy which can be associated with an increased risk of treatment related late effects warranting investigation of other active agents. The malignant cells of NLPHL universally express CD20, therefore therapy with rituximab (R), the monoclonal anti-CD20 antibody, is a targeted option. We report our experience with R as front-line treatment for patients with NLPHL. Methods: Patients with newly diagnosed NLPHL and measurable disease were treated with R at 375 mg/m2 administered weekly × 4 or, after protocol amendment (February 2003) with R followed by 4 doses of R maintenance (RM) administered every 6 months for 2 years. Restaging studies were performed at 1, 3 and 6 months and then every 6 months until progression. All pathology was centrally reviewed. Results: Nineteen patients were enrolled between May 1999 and September 2006. The median age at treatment was 45 years (range 17–63), stage I (n=6), stage II (n=7), stage III (n=6). Ten patients were treated with R alone and 9 with R+RM. The median follow-up for R patients is 8.8 years (5–11.4) and for R+RM patients is 5 years (2.5–7.6). At the end of induction therapy with R alone, the overall response rate was 100% [complete response (CR) (n=10), CR unconfirmed (n=2) and partial response (n=7)]. The median progression free survival (PFS) for patients treated with R alone and R+RM is 50 months and 67 months, respectively (p=0.7; log rank test) and median overall survival (OS) not reached. The median follow up for patients without progressive disease at the time of this analysis was 6.9 years (range 2.5–11.5). The estimated PFS at 5 years is 51.7%, [95% CI 33.2–80.4] and at 10 years 35.4% [95% CI 17.7–70.8]. There was no difference in median PFS between patients with stages I-II versus III (5.6 years and 4.15 years respectively, p=0.58 [log rank test]). The estimated OS at 5 years is 93.3%, [95% CI 81.5–100] and 10 years 76% [95% CI 55.4–100]. Ten patients progressed (5 treated with R alone, 5 treated with R+RM) of whom 6 transformed to an aggressive B cell lymphoma (biopsy proven) at a median of 4.2 years [range 0.9–8]. Five of the 6 transformed patients had abdominal disease at initial diagnosis (stage III, n=4). Three patients died (2 aggressive NHL, 1 unknown). Conclusion: Rituximab is an active single agent in the treatment of newly diagnosed NLPHL with a median PFS of 5.6 years. R+ RM resulted in a non-significant increase in PFS compared to R alone. In this series, abdominal involvement was associated with transformation to an aggressive B cell lymphoma underscoring the need for biopsy at relapse. These results demonstrate a pattern of late relapse following rituximab, at least as great as the historical data with RT or RT + CT. Although R alone achieved proof of concept for a targeted therapy, its use should remain investigational as primary therapy of NLPHL. Disclosures: Advani: Genentech Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding. Off Label Use: Rituximab. Anti-CD20 agent that targets CD20 on NLPHL cells. Horning:Genentech: Employment, Equity Ownership.

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Impact Of a Federal Program On response Rate & Survival, In a Cohort Of Patients With Diffuse Large B- Cell Lymphoma. Analysis In a Single National Reference Institution In Mexico

Blood ◽

10.1182/blood.v122.21.5608.5608 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5608-5608

Author(s):

Myrna Candelaria ◽

Juan Labardini ◽

Ana Florencia Ramirez ◽

Alejandro Aviles ◽

Enrique Estrada-Lobato ◽

...

Keyword(s):

B Cell ◽

Response Rate ◽

Conflicts Of Interest ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Standard Of Care ◽

Federal Program ◽

Large B Cell Lymphoma ◽

Large B Cell

Abstract The actual standard of care of Diffuse Large B-Cell Lymphoma (DLBCL) includes rituximab in combination with chemotherapy, with overall response rates up to 76 %. However, this treatment may not be accessible to many patients because of limited economical resources, particularly in developing countries, where most of the treatment must be paid from the pocket of patients or their families. In Mexico, since 2011 a Federal program has fully covered the treatment of patients with DLBCL. At the Instituto Nacional de Cancerología (INCan) in Mexico city 214 patients with ths disease have been treated without cots with the standard of care. The mean age at diagnosis was 56.7 +15.9 (22-91). This series of cases was compared with a retrospective analysis of cases with DLBCL seen at the INCan between 2006-2008 None A total of 264 cases were retrospectively analyzed. No differences were found in demographic and clinical characteristics at the time of diagnosis. However, a clear positive impact was found in the group that received full treatment thanks to this new social coverage by this new social security program. The follow-up and completion of treatment was 99%., In contrast: from 264 in the retrospective group, 209 (79 %) were treated, but only 29 (10.9 %) were able to receive an optimal treatment, including rituximab. These differences in treatments had a clearly impact on the response rate, as shown in the following table:A: Retrospective cases.N (%) B: Cohort.N (%) p Patients. 264 214 -- Treatment:CHOP-R (standard of care)CHOP0-2 cycles** 2918055** 20410*-- 0.001 Response (all patients) :CompletePartialStable diseaseProgressiveNot evaluable, lost of follow up 103 (39)31 (11.7)11 (4.1 )24 (9)95 (36) 124 (58)19 (8.8)0 --29 (13.5)-- 0.001 Relapse rate (%) 93 (35 %) 43 (20%) 0.0001 *7 patients did not received rituximab because of HBV & 3 HIV positive had < 100 absolute CD4 counts.**Patients who abandoned treatment because of reduced economical resources. These results demonstrate the importance of social programs that may accessible standard treatment options in countries with limited resources. Disclosures: No relevant conflicts of interest to declare.

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Concomitant Radiochemotherapy In The Treatment Of Refractory Or Locally Relapsed Diffuse Large B-Cell Lymphoma: A Single Center Retrospective Study

Blood ◽

10.1182/blood.v122.21.5114.5114 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5114-5114

Author(s):

Emmanuel Gyan ◽

Alban Villate ◽

Severine Lissandre ◽

Lotfi Benboubker ◽

Martine Delain ◽

...

Keyword(s):

B Cell ◽

Conflicts Of Interest ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Complete Response ◽

Hematological Toxicity ◽

Severe Toxicity ◽

Large B Cell Lymphoma ◽

Large B Cell

Abstract Introduction Primary refractory Diffuse Large B-Cell Lymphoma (DLBCL) as well as relapse after salvage therapy displays a poor prognosis. Salvage radiation therapy alone does not provide sufficient disease control on locally chemoresistant DLBCL. Autologous stem cell transplantation (ASCT) provides the best progression-free survival when salvaged patients are transplanted in Complete Response (CR). The objective of this study was to assess the effectiveness of CCR in locally relapsed or refractory DLBCL, followed by ASCT in responding patients. Material and methods We report the outcome of consecutive patients with locally relapsed or refractory lymphoma for which a decision of CRC was taken in a single institution. Each patient has been assessed by CT or PET-scan. The CRC regimen consisted in 3 cycles of Rituximab (375 mg/m² day 1), CDDP (30 mg/m² 3 days 1-3) and VP16 (120 mg/m² days 1-3) at 21 days intervals, with concomitant radiotherapy delivered to the residual disease sites, administrated in 2 Gy fractions per day to a total dose of 30 Gy, starting on day 1 of the second cycle. Responding patients received ASCT with a BEAM conditioning at the end of the procedure. Extra-hematological toxicity was ranked according to the Common Terminology Criteria for Adverse Events. Tumor response was evaluated according to IWG 1999 at 1 month after the last cycle of CRC, three months after ASCT if performed and during a quarterly follow-up. Results We identified 13 patients with localized chemoresistant DLBCL from January 2002 to April 2011 including 12 primary refractory forms. The median age was 56 years (20-76), 12 of 13 patients had received at least two lines of chemotherapy before inclusion with anthracycline and cisplatin. 11 patients achieved a partial response (85%) and 4 of them (31%) a complete response after the CRC. 8 (61.5%) patients were transplanted 1 month after the last cycle of CRC. 7 patients have relapsed within 6 months after the end of treatment. After a median follow-up of 37 months (range 21-125) for the surviving patients, 7 patients are alive and free of disease. The overall survival is 54%, and all surviving patients had been transplanted. No severe toxicity was reported. Conclusion CRC should be considered as an option in the therapeutic arsenal in refractory or locally relapsed DLBCL, especially in patients eligible for ASCT. Further research on CRC is warranted. Disclosures: No relevant conflicts of interest to declare.

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