Ctdna Monitoring in Predicting Relapse of Primary Mediastinal B-Cell Lymphoma

Background: Primary mediastinal B-cell lymphoma (PMBCL) is a rare subtype of aggressive B-cell lymphoma. The majority of relapses occur within the first few months resulting in a dismal prognosis, thus we need to identify the risk of early relapse. Circulating tumor DNA (ctDNA)-based response assessment may enable response adapted therapy and early prognostication. In this study, we aim to clarify the role of ctDNA-monitoring in early prediction of relapse. Methods: We retrospectively analyzed the characteristics of 38 patients with PMBCL. The genetic sequencing and ctDNA monitoring were conducted by target next-generation sequencing (NGS). Results: The median age was 32 years old and 26 (68.4%) were female. Most cases (31/38, 81.6%) were diagnosed with stage I or II disease and fourteen (36.8%) cases present with extranodal involvement. The 5-year PFS and OS for PMBCL patients were 65.7 and 72.1%, respectively. High IPI score were associated with poor survival by univariate analysis. The complete response (CR) rate and overall response rate of R-CHOP was similar to R-EPOCH (69.2% vs. 70.0%, P =1.000 and 84.6% vs. 95.0%, P =0.547, respectively), however the 5-year PFS and OS rate for R-EPOCH seems longer than those for the R-CHOP (PFS 82.9% vs. 53.8%, P=0.0569; OS 92.9% vs. 60.6%, P=0.0567). Radiotherapy was less delivered in the patients who received R-EPOCH than R-CHOP (5.0% vs.53.8%, P=0.003) and had no impact on prognosis. We performed genetic sequencing on twenty-three cases. STAT6(15/23, 65.2%), SOCS1(13/23, 56.5%), TNFAIP3(13/23, 56.5%) were the most common affected genes in both response and refractory/relapsed patients. Cell cycle, FoxO signaling pathway and TNF signaling pathway were more frequently involved in refractory patients. ctDNA monitoring was conducted in 16 cases and fifteen cases show undetectable ctDNA after a median of 2 (range from 1 to 5) cycles and one refractory case presented with durable positive ctDNA. Among 4 relapse cases, 3 had prior detectable ctDNA half a month earlier before imaging manifestations of relapse. Regarding prediction of relapse, positive predictive value of ctDNA is 100%. Conclusions: Intensive induction chemotherapy can improve prognosis of PMBCL and ctDNA precisely predicted relapse. As most cases relapse within a few months, ctDNA-monitoring is crucial to improve prognosis. Disclosures No relevant conflicts of interest to declare.

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Characteristics of primary extranodal marginal zone B-cell lymphoma in Korea: conjunctiva versus other ocular adnexa

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2017-310741 ◽

2017 ◽

Vol 102 (4) ◽

pp. 502-508 ◽

Cited By ~ 3

Author(s):

Seung Wan Nam ◽

Kyung In Woo ◽

Yoon-Duck Kim

Keyword(s):

B Cell ◽

Marginal Zone ◽

Cell Lymphoma ◽

Univariate Analysis ◽

B Cell Lymphoma ◽

Complete Response ◽

Negatively Associated ◽

Systemic Involvement ◽

Tumour Location ◽

Clinical Records

AimsTo compare the clinical characteristics and prognosis of primary conjunctival versus other ocular adnexal extranodal marginal zone B-cell lymphoma (EMZL).MethodsRetrospective review of clinical records for all consecutive patients with primary ocular adnexal EMZL treated from March 1995 to December 2015.Results198 patients were evaluated including 81 with primary conjunctival and 117 with other ocular adnexal EMZL. Conjunctival EMZL was found at a younger age (40.3±10.3vs 54.3±13.4 years, p<0.0001) with a female predilection (75.3%vs35.9%, p<0.0001) and had a higher rate of bilaterality (40.7%vs11.1%, p<0.0001) and a lower rate of systemic involvement (1.2%vs9.4%, p=0.030) compared with other ocular adnexal EMZLs. Conjunctival EMZL also showed a higher rate of complete response to primary treatment (98.8%vs89.5%, p=0.016) than other ocular adnexal EMZLs; however, recurrence and lymphoma-related death rates were not different between the two groups (p>0.05). Kaplan-Meier estimates for disease-specific survival at 5 and 10 years were 98.2% and 98.2% in conjunctival and 98.6%, respectively, and 95.2% in other ocular adnexal EMZLs. Univariate analysis showed that systemic involvement was negatively associated with conjunctival tumour location and positively associated with age (OR=0.35 and OR=1.05, p=0.045 and p=0.012, respectively), and treatment response was positively associated with conjunctival tumour location and negatively associated with age (OR=3.02 and OR=0.95, p=0.035 and p=0.009, respectively).ConclusionsConjunctival EMZL shows unique demographic characteristic compared with other ocular adnexal EMZLs. Long-term follow-up is required due to late recurrence in ocular adnexal EMZL.

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R-CHOP21 Vs R-CHOP14 in 950 Diffuse Large B-Cell Lymphoma Patients: Results of a Multicentre Retrospective Study Form Italian Lymphoma Foundation (FIL)

Blood ◽

10.1182/blood.v120.21.1615.1615 ◽

2012 ◽

Vol 120 (21) ◽

pp. 1615-1615

Author(s):

Luigi Rigacci ◽

Benedetta Puccini ◽

Maria Giuseppina Cabras ◽

Luca Nassi ◽

Alberto Fabbri ◽

...

Keyword(s):

B Cell ◽

Conflicts Of Interest ◽

Cell Lymphoma ◽

Univariate Analysis ◽

B Cell Lymphoma ◽

Hematological Toxicity ◽

Bulky Disease ◽

Symptomatic Disease ◽

Large B Cell Lymphoma ◽

Large B Cell

Abstract Abstract 1615 Background: Diffuse large B cell lymphoma (DLBCL) is one of the most common types of non-Hodgkin's lymphoma. R-CHOP21 (C21) is considered the standard therapy but a large number of studies have tested R-CHOP14 (C14). Aims: The aim of our study was to evaluate retrospectively a cohort of patients (pts) treated with C21 or C14 and to compare the efficacy of the therapy. Methods: All pts with diagnosis of DLBCL or follicular grade IIIb lymphoma, treated with curative intent in 9 Italian Hematological Centers, were accrued. All patients treated with C14 used G-CSF as primary prophilaxis, and only elderly (over 70 years) patients treated with C21 used G-CSF as primary prophilaxis. Results: From january 2002 to june 2011, 950 pts were accrued, 643 pts were treated with C21 and 307 were treated with C14. The median age was 63 (range 19–89). The two cohorts of pts were balanced for all clinical characteristics a part for age (<60 or >60 years) with more aged pts in C21 arm (p 0.001), bone marrow positivity and more than 3 lymph node stations involved that were higher in C14 arm (p: 0.05 and p: 0.001). After induction therapy 751 pts (79%) obtained a complete remission: 501/643 (78%) after C21 and 250/307 (81%) after C14. The remaining pts obtained partial response in 110 and 48 or no response in 32 and 9 respectively for C21 and C14. After a median period of observation of 38 months 104 pts relapsed (14%), 68 (65%) in the C21 arm and 36 (35%) in the C14 arm. After a median observation period of 3 years, considering the two therapies, C21 vs C14, no differences were reported in OS (Figure 1), PFS (Figure 2) and DFS: 80% vs 84%, 69% vs 71% and 54% vs 56% respectively. In univariate analysis OS was lower in older pts (azard ratio (ar): 2.57), IPI 2 (ar: 2.09), IPI 3 (ar: 4.36), IPI 4–5 (ar: 6.36), bulky disease (ar: 1.70), symptomatic disease (ar: 2.23). In multivariate analysis factors which mantained significantly worst prognosis were older age (ar: 1.35), IPI 2 (ar: 1.95), IPI 3 (ar: 3.76), IPI 4–5 (ar: 5.01) and bulky disease (ar: 1.43). As expected hematological grade III/IV toxicity was more frequent in pts treated with C14. No differences in extra-hematological toxicity were observed. Secondary malignancies were reported: 7 in C21 and 3 in C14. After 3 years of median observation 188 pts are dead: 137 (73%) in C21 and 51 (27%) in C14 (not statistically significant, p:0.08). The large majority of pts are dead for disease progression or relapse. Conclusions: In conclusion our results confirm that C14 do not improve the results of the standard C21 in the whole lymphoma population. Dose dense therapy did not affect OS or PFS also analysing sub group of pts. As expected a higher frequency of neutropenia was observed in C21 arm but did not translate in increasing infection rate. Further prospective randomized studies are needed to verify this preliminary observations. Disclosures: No relevant conflicts of interest to declare.

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Doublet Versus Triplet PET: Is END of Therapy PET Needed IF Interim PET Is Negative in Hodgkin'S or Diffuse Large B CELL Lymphoma?

Blood ◽

10.1182/blood.v128.22.5354.5354 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5354-5354

Author(s):

Imran K Tailor ◽

Bilal Btoosh ◽

Shaimaa Hamdy ◽

Shanker Raja ◽

Mohammed O Alharbi ◽

...

Keyword(s):

B Cell ◽

Conflicts Of Interest ◽

Cell Lymphoma ◽

Progression Free Survival ◽

B Cell Lymphoma ◽

Standard Of Care ◽

Complete Response ◽

Interim Pet ◽

Large B Cell Lymphoma ◽

Large B Cell

Abstract Introduction: Baseline (PETb) and end of therapy (PETe) FDG PET is standard of care in the management of hodgkin's lymphoma (HL) and diffuse large B cell lymphoma (DLBCL). The role of interim PET (PETi) in HL is well established while its role in DLBCL is not well defined. We evaluated the utility of triPET (PETb, PETi and PETe ) in management of these two lymphomas. Methods: Retrospective review of PET archives revealed a total of 37 pts (HL=22, DLBCL=15). TriPET were acquired per accepted protocol. SUVmax and Deauville scores (DSc) were obtained from five target lesions, the average i.e. composite SUVmax & DSc were computed for each pt. Statistical analyses were performed with the composite maxSUV (cSUV) and Deauville scores (cDSc) (using EXCEL). Following statistics were performed (separately and combined in HL and DLBCL); mean+SD, PPV and NPV for complete response (CR) Vs. progressive disease (PD) on PETi using the following variables 1. cSUV and 2. cDSc and 3. delta change (DELT). Median progression free survival (PFS) was the clinical endpoint for response. Results: The mean PFS in our group was 17 and 15 months in HL and DLBCL respectively. Using cut off thresholds for intP to predict CR at cSUV<=2.0, , cDSC<=2.0 and DELT >=80%,. In HL: for cSUV- PPV 67%, NPV 95%; for DELT of cSUV PPV 100%, NPV 95%; for cDSC-PPV 30%, NPV 100%. In DLBCL: for cSUV- PPV 25%, NPV 100%; for DELT of cSUV PPV 33%, NPV 100%; for cDSC- PPV 50%, NPV 100%. Conclusion: The results from our series suggest that PETi has a role not only in HL but in DLBCL as well. Our modest cohort suggests that a negative PETi in DLBCL had a NPV of 100% across cSUV, cDSc and DELT, with regards to CR. Our data also suggests that PETe is not needed if PETi is -ve. While in HL subset, our results concur with results from other groups, this needs to be validated in a larger series. Disclosures No relevant conflicts of interest to declare.

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Outcomes of Cardiac Diffuse Large B-Cell Lymphoma in the Rituximab Era

Blood ◽

10.1182/blood-2020-134267 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 9-10

Author(s):

Taha Al-Juhaishi ◽

Ghaith Abu Zeinah ◽

Sadeer Al-Kindi

Keyword(s):

B Cell ◽

Survival Data ◽

Conflicts Of Interest ◽

Cell Lymphoma ◽

Univariate Analysis ◽

B Cell Lymphoma ◽

Disease Stage ◽

P Value ◽

Large B Cell Lymphoma ◽

Large B Cell

Introduction: Cardiac lymphomas are very rare with diffuse large B-cell lymphoma (DLBCL) considered to be the most common histology. These lymphomas can be either local "primary cardiac" disease, or part of dissemination by systemic lymphoma. There is limited data regarding outcomes of patients with this disease. We sought to evaluate the outcomes of cardiac DLBCL in both pre- and rituximab eras using a large retrospective database. Methods: The public Surveillance, Epidemiology and End Results (SEER) database was used to identify all patients diagnosed with DLBCL and heart as the primary disease site. Data cutoff in the database was in 2016. Patients with missing date of diagnosis or survival data were excluded. Patients were divided into two groups based on diagnosis year, with rituximab cohort included all DLBCLs diagnosed in 2006 and later (2006 was FDA approval year of rituximab in untreated DLBCL). Treatment effect (surgery, radiation, chemotherapy) was analyzed when available. survival was estimated using the Kaplan-Meier method, and compared using Log-Rank test. Cox proportional hazards models were used for adjusted survival analyses. Results: Total of 106 patients were included in the final analysis, baseline characteristics are summarized in table 1. Median age at diagnosis was 69.5 years with only about 10% of patients being 50 years or younger. Most patients were white 71 (67%), had local stage I/II disease 68 (64.2%), and belonged to the rituximab era group 71 (67%). Most patients had chemotherapy 82 (77.4%), while only 25 (23.6%) had surgery, and 16 (15.1%) had radiotherapy. Median overall survival (OS) for the entire cohort was 22 months (0-292). Median OS was 16 months (95% CI, 0.55 -31) for the pre-rituximab group, and was 26 months (95% CI, 7.5 - 45) for the rituximab group which were not statistically different (p-value =0.340). Median lymphoma-specific survival (LCS) was 30 months (95% CI, 8.0 -52) for the pre-rituximab group, and was 36 months (95% CI, 16 - 158) for the rituximab group which were not statistically different (p-value =0.295). OS and LCS were also not different between the two era groups when stratified by chemotherapy (figure 1). On univariate analysis, Chemotherapy was associated with better OS [HR = 0.472, 95% CI (0.277-0.806); p-value = 0.006] but not LCS [HR = 0.690, 95% CI (0.341-1.396); p-value = 0.302]. Using a multivariate analysis model, both OS and LCS were associated with lymphoma stage, insurance status and age but not with diagnosis era or chemotherapy (table 2). Conclusion: Cardiac DLBCLs are rare and affecting mostly the elderly. No significant improvement in outcomes were noted in the current rituximab era. Age, disease stage, and having health insurance were associated with better outcomes. The role of chemotherapy needs further evaluation in larger studies. Disclosures No relevant conflicts of interest to declare.

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An Effective Salvage Treatment Using Rituximab, Ifosfamide, Etoposide, Cytarabine, and Dexamethasone (R-IVAD) for Patients with Relapsed or Refractory Aggressive B-Cell Lymphoma

Blood ◽

10.1182/blood.v116.21.1759.1759 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1759-1759

Author(s):

Katsuhiro Miura ◽

Kazuhiro Takei ◽

Sumiko Kobayashi ◽

Yujin Kobayashi ◽

Toshitake Tanaka ◽

...

Keyword(s):

Stem Cell ◽

B Cell ◽

Conflicts Of Interest ◽

Cell Lymphoma ◽

Performance Status ◽

B Cell Lymphoma ◽

Complete Response ◽

High Dose ◽

Salvage Regimen ◽

Aggressive B Cell Lymphoma

Abstract Abstract 1759 Background The prognosis of patients with relapsed or refractory aggressive B-cell lymphoma after the conventional first line chemotherapy is still disappointing. Although several rituximab combined salvage regimens were reported, the optimal treatment has not yet been established. We therefore evaluated the efficacy and toxicity of a non-anthracycline based salvage regimen, consisting of rituximab, ifosfamide, etoposide, cytarabine and dexamethasone (R-IVAD) in patients with relapsed or refractory aggressive B-cell lymphoma. Patients and methods Patients with relapsed or refractory CD20-positive diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma grade 3 (FL G3) were consecutively enrolled in this treatment. R-IVAD consisted of rituximab (375 mg/m2 on day -2), ifosfamide (1500 mg/m2 on day 1–5), etoposide (150 mg/m2 on day 1–3), cytarabine (100 mg/m2 on day 1–3) and dexamethasone (40 mg/body on day 1–3). Treatment was given every 3 weeks up to a total of 3 courses with support of granulocyte colony stimulating factor. For responders under 65 years old with good performance status (PS), we planed peripheral stem cell collection after the third cycle of R-IVAD and consolidating high-dose chemotherapy (HDC) with cycrophosphamide (60 mg/kg on day -7,-6), etoposide (500 mg/m2 on day -6, -5, -4) and ranimustine (250 mg/m2 on day -3, -2) followed by autologous stem cell transplantation (ASCT). Results Thirty-two patients (25 DLBCL and 7 FL G3) with a median age of 64 years old (range 38–79) participated in this study and received an average of 2.6 cycles of R-IVAD. There were 21 relapsed and 11 primary refractory patients. The overall response (OR) and the complete response (CR) rate were 72% and 56% respectively. The OR rate of relapsed patients was significantly higher than that of primary refractory patients (86% vs. 45%, p=0.035). With a median 16 months (range 2–99) of follow up, the 2-year overall survival (OS) and the event-free survival (EFS) for all patients were 55% and 36% respectively. Of the 11 eligible patients, 10 successfully proceeded to HDC/ASCT with an average of 5.5 × 106/kg of harvested CD34-positive cells, resulting in the 2-year OS of 90%. No treatment related death was observed during the investigation. Multivariate analysis revealed that the age > 60 years, PS ≥ 2, extranodal sites ≥ 2, and primary refractory disease were independently associated with worse survival. Conclusion R-IVAD regimen, which efficiently mobilizes peripheral stem cells, is a safe and efficacious alternative for patients with relapsed or refractory aggressive B-cell lymphoma. Disclosures: No relevant conflicts of interest to declare.

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Efficacy of Yttrium-90 Iburitumomab Tiuxetan for Early Relapsed/Refractory Indolent B-Cell Lymphoma: A Single Institute Retrospective Analysis in the Rituximab Era

Blood ◽

10.1182/blood-2018-99-112782 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5333-5333

Author(s):

Keiichi Nakata ◽

Shigeo Fuji ◽

Ryo Nakata ◽

Kazuhito Tsutsumi ◽

Shuhei Kida ◽

...

Keyword(s):

Follicular Lymphoma ◽

B Cell ◽

Conflicts Of Interest ◽

Cell Lymphoma ◽

Univariate Analysis ◽

B Cell Lymphoma ◽

Significant Prognostic Factor ◽

Hematopoietic Stem ◽

The Impact ◽

Yttrium 90

Abstract Introduction: Indolent B-cell lymphoma is a type of non-Hodgkin's lymphoma that grows slowly and is not a curative disease. Yttrium-90 (90Y) iburitumomab tiuxetan is used in patients with relapsed/refractory indolent B-cell lymphoma, data is still limited in the rituximab era. In addition, previous studies did not assess the impact of early progression of disease within 2 years (POD24) which was reported to be associated with a poor prognosis in follicular lymphoma (Casulo et al, J Clin Oncol 2015) on the efficacy of 90Y iburitumomab tiuxetan. Thus, here we assessed the efficacy of 90Y iburitumomab tiuxetan in relapsed/refractory indolent B-cell lymphoma, and analyzed the impact of POD24 in this setting. Methods: We retrospectively analyzed the clinical outcomes of 51 patients with a relapsed/refractory indolent B-cell lymphoma who received 90Y iburitumomab tiuxetan at our institute from February 2009 to January 2018. POD24 was defined as progression within 24 months from the beginning of induction chemotherapy. Survival outcomes including overall survival (OS) and progression-free survival (PFS) were analyzed by Kaplan-Meier analysis and Cox proportional hazard models. Results: The median age was 64 years (range 37-88 years) at the time of receiving 90Y iburitumomab tiuxetan, and 29 (56.9%) were male. Disease subtypes were as follows: follicular lymphoma (n=44, 86.3%), mantle cell (n=4, 7.8%), marginal zone (n=2, 3.9%), and MALT lymphoma (n=1, 2.0%). The median number of previous regimens was 2 (range 1-9) and included rituximab-based therapy in all patients. Disease status at the time of receiving 90Y iburitumomab tiuxetan were as follows: complete remission (CR n=3, 5.9%), partial remission (PR n=13, 25.5%), stable disease (SD n=3, 5.9%), progression disease (PD n=32, 62.7%). The median follow-up time was 3.7 years (range 0.3-8.8 years) and overall response rate (ORR) was 94.1% (CR 56.9%, PR 37.3%). The ORR in patients with POD 24 was 95.0% (CR 60.0%, PR 35.0%), compared to 93.5% (CR 54.8%, PR 38.7%) with non-POD24. The 3-year OS and PFS rates for all patients receiving 90Y iburitumomab tiuxetan were 83.6% and 41.0%, respectively. POD24 was a significant prognostic factor for PFS in univariate analysis (1.2 years in patients with POD24 vs. 3.3 years in patients with non-POD24, (P=0.02) (Figure1). In multivariate analysis, POD24 was an independent prognostic marker of PFS (hazard ratio (HR) 0.43, 95% confidence interval (CI) 0.22-0.87, P=0.02). Conclusion: 90Y iburitumomab tiuxetan was highly effective in patients with relapsed/refractory indolent B-cell lymphoma patients. However, in patients with POD24, duration of response was short. Thus, another treatment strategy including hematopoietic stem cell transplantation should be considered. Disclosures No relevant conflicts of interest to declare.

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A Phase II Trial of Alemtuzumab (Campath) with DA-EPOCH-R in Relapsed or Refractory Diffuse Large B-Cell Lymphoma and Hodgkin Lymphoma

Blood ◽

10.1182/blood.v120.21.3709.3709 ◽

2012 ◽

Vol 120 (21) ◽

pp. 3709-3709 ◽

Cited By ~ 1

Author(s):

Cliona Grant ◽

Kieron Dunleavy ◽

Julieanne Hessler ◽

Seth M. Steinberg ◽

Stefania Pittaluga ◽

...

Keyword(s):

B Cell ◽

Hodgkin Lymphoma ◽

Mononuclear Cells ◽

Conflicts Of Interest ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Complete Response ◽

Large B Cell Lymphoma ◽

Age Range ◽

Large B Cell

Abstract Abstract 3709 Background: In diffuse large B-cell lymphoma (DLBCL), stromal signatures are predictive of outcome in newly diagnosed patients treated with R-CHOP. These signatures, termed 'stromal 1' and 'stromal 2' are associated with genes expressed by infiltrating mononuclear cells. The stromal 2 signature includes genes associated with angiogenesis and is associated with a poor outcome. Hence, targeting reactive cells in the microenvironment is a rational therapeutic strategy in DLBCL. In Hodgkin lymphoma (HL), the reactive macrophages surrounding Hodgkin Reed Sternberg (HRS) cells are associated with an adverse outcome and may provide survival signals. CD52 is highly expressed in many of these cells in the microenvironment and in most cases of DLBCL. Methods: We combined alemtuzumab (a monoclonal antibody against CD52) with DA-EPOCH-R to target reactive cells in the microenvironment and positive tumor cells. Alemtuzumab (30 mgs on day 1) was administered intravenously before DA-EPOCH-R (as previously described) and responding patients received up to 6 cycles of therapy. Results: Characteristics of 28 patients accrued: median age (range) 44 (22–72); male sex 15 (54%); stage III or IV disease 20 (71%); median prior regimens (range) 2 (1–6); and prior autologous transplant 7 (25%). Enrolled histologies were HL 12 (43%); DLBCL 10 (36%); and primary mediastinal B-cell lymphoma 6 (21%). Responses by histological subtype are shown in the attached table. The regimen was particularly effective in patients with HL with a CR rate of 73%. At 12 months (with 21 months median potential follow-up), the OS and PFS probabilities for all patients were 68% and 18% respectively. Toxicities included: treatment related mortality (sepsis) in 1 patient; febrile neutropenia in 16%; and grade 4 thrombocytopenia 15% of cycles. CMV reactivation was observed in 52% of patients in the setting of anti-viral prophylaxis. Conclusions: Combining alemtuzumab with DA-EPOCH-R is feasible. Patients with a diagnosis of HL had a very high complete response rate. Accrual continues. 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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Ibrutinib in B-cell lymphoma: single fighter might be enough?

Cancer Cell International ◽

10.1186/s12935-020-01518-y ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Chao Xue ◽

Xin Wang ◽

Lingyan Zhang ◽

Qingyuan Qu ◽

Qian Zhang ◽

...

Keyword(s):

B Cell ◽

Signaling Pathway ◽

Cell Lymphoma ◽

Critical Role ◽

B Cell Lymphoma ◽

Cell Receptor ◽

High Response Rate ◽

Main Body ◽

Combination Strategies ◽

Bcr Signaling

Abstract Background In recent years, the B cell receptor (BCR) signaling pathway has become a “hot point” because it plays a critical role in B-cell proliferation and function. Bruton’s tyrosine kinase (BTK) is overexpressed in many subtypes of B-cell lymphoma as a downstream kinase in the BCR signaling pathway. Ibrutinib, the first generation of BTK inhibitor, has shown excellent antitumor activity in both indolent and aggressive B-cell lymphoma. Main body Ibrutinib monotherapy has been confirmed to be effective with a high response rate (RR) and well-tolerated in many B-cell lymphoma subgroups. To achieve much deeper and faster remission, combination strategies contained ibrutinib were conducted to evaluate their synergistic anti-tumor effect. Conclusions For patients with indolent B-cell lymphoma, most of them respond well with ibrutinib monotherapy. Combination strategies contained ibrutinib might be a better choice to achieve deeper and faster remission in the treatment of aggressive subtypes of B-cell lymphoma. Further investigations on the long-term efficacy and safety of the ibrutinib will provide novel strategies for individualized treatment of B-cell lymphoma.

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