scholarly journals Tisagenlecleucel in relapsed/refractory diffuse large B-cell lymphoma patients without measurable disease at infusion

2019 ◽  
Vol 3 (14) ◽  
pp. 2230-2236 ◽  
Author(s):  
Michael R. Bishop ◽  
Richard T. Maziarz ◽  
Edmund K. Waller ◽  
Ulrich Jäger ◽  
Jason R. Westin ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Preliminary Evidence ◽  
Large B Cell Lymphoma ◽  
Grading Scale ◽  
Control Disease ◽  
Grade 3 ◽  
Large B Cell

Abstract Tisagenlecleucel demonstrated high rates of durable responses in adult patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL) in the JULIET trial. Most patients (92%) received bridging therapies to control disease after study entry and before tisagenlecleucel infusion. Here, we examine the efficacy and safety of tisagenlecleucel in the subset of 7 patients who achieved complete response (CR) after bridging therapy and before tisagenlecleucel infusion. Tisagenlecleucel rapidly expanded in all 7 patients, and the transgene levels were measurable for up to 2 years after infusion. After infusion, all 7 patients were still in CR at the month 3 evaluation, and 5 of 7 patients remained progression-free >12 months. Adverse events were similar to the overall JULIET population. Cytokine release syndrome (CRS) was reported in 4 of 7 patients (grade 2 = 2 and grade 3 = 2 using the Penn grading scale), and 1 patient experienced grade 1 neurotoxicity. No patient required tocilizumab or steroids for CRS management. These data provide preliminary evidence of tisagenlecleucel efficacy in patients with r/r DLBCL without detectable disease after bridging or salvage therapies and warrant further investigation of tisagenlecleucel as consolidative therapy in future trials. This trial was registered at www.clinicaltrials.gov as #NCT02445248.

Yttrium-90 Ibritumomab Tiuxetan Followed by Rituximab Maintenance as Treatment for Patients with Diffuse Large B-Cell Lymphoma Are Not Candidates for Autologous Stem Cell Transplant

2015 ◽  
Vol 133 (4) ◽  
pp. 347-353 ◽  
Author(s):  
Jon E. Arnason ◽  
Katarina Luptakova ◽  
Jacalyn Rosenblatt ◽  
Dimitrios Tzachanis ◽  
David Avigan ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Cell Transplant ◽  
Ibritumomab Tiuxetan ◽  
Rituximab Maintenance ◽  
Large B Cell Lymphoma ◽  
Grade 3 ◽  
Large B Cell

Background: Not all patients with diffuse large B-cell lymphoma (DLBCL) are candidates for aggressive regimens. 90Y ibritumomab tiuxetan (90Y-IT), an anti-CD20 radionuclide-conjugated antibody, has demonstrated clinical efficacy in DLBCL with a favorable toxicity profile. Methods: This phase II trial investigated the overall response rate (ORR), event-free survival (EFS), overall survival (OS) and toxicity of treatment with 90Y-IT (0.4 or 0.3 mCi 90Y/kg based on platelets) followed by rituximab maintenance therapy in patients with DLBCL not candidates for transplant. Results: 25 patients were enrolled. At best response 8 patients obtained a complete response (CR) and 1 a partial response (ORR 36%). Median EFS was 2.5 months and OS 8.1 months. No patient who obtained CR later relapsed systemically. Two patients were free of disease at the 61- and 100-month follow-ups; 65% had grade 3/4 thrombocytopenia, but no significant bleeding was observed. Grade 3 nonhematologic toxicity occurred in 36%. Patients who had progressed through a rituximab-containing regimen responded poorly. Conclusion: The ORR of 36% with 90Y-IT as salvage therapy for DLBCL while inferior to more aggressive regimens is significant with acceptable toxicity. For a subset of patients not candidates for salvage with autologous transplant, this treatment strategy can produce a durable, long-lasting remission.

scholarly journals Results of a UK real world study of polatuzumab vedotin, bendamustine, and rituximab for relapsed/refractory large B-cell lymphoma

2022 ◽  
Author(s):  
Michael Northend ◽  
William Wilson ◽  
Wendy Osborne ◽  
Christopher P. Fox ◽  
Andrew John Davies ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Preliminary Evidence ◽  
Cell Transplant ◽  
T Cell Therapy ◽  
Large B Cell Lymphoma ◽  
Car T ◽  
Large B Cell

The addition of polatuzumab vedotin to bendamustine and rituximab (Pola-BR) has been shown to improve overall survival (OS) in stem cell transplant (SCT)-ineligible patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). It is also increasingly used as bridging to CAR T-cell therapy (CAR-T). We retrospectively analysed the efficacy of Pola-BR in 133 patients at 28 UK institutions. Treatment intent was bridging to CAR-T for N=40, re-induction with planned SCT for N=13 and stand-alone treatment for N=78. The overall response rate (ORR) was 57.0% (complete response (CR) 32.8%). After median 7.7 months follow-up, median PFS and OS were 4.8 months and 8.2 months respectively. For stand-alone treatment shortened PFS was associated with bulk disease (>7.5cm) (HR 2.32 (95% CI 1.23-4.38), p=0.009), >1 prior treatment (HR 2.17 (95% CI 1.19-3.95), p=0.01) and refractoriness to the last treatment (HR 3.48 (95% CI 1.79-6.76), p<0.001). For CAR-T bridging the ORR was 42.1% (CR 18.4%) and for treatment after CAR-T failure the ORR was 43.8% (CR 18.8%). These data demonstrate efficacy for Pola-BR as a treatment for SCT-ineligible patients with R/R DLBCL, help to delineate which patients may benefit most, and provide preliminary evidence of efficacy as bridging to CAR-T and after CAR-T failure.

scholarly journals Large B-Cell Lymphoma with T-Cell–Rich Background and Nodules Lacking Follicular Dendritic Cell Meshworks: A Case Report with Complete Response to Chemotherapy and a Review of the Literature

2020 ◽  
Vol 5 (11) ◽  
pp. 561-565
Author(s):  
Walid Shalata ◽  
Ismaell Massalha ◽  
Kayed Al-Athamen
Keyword(s):  
T Cell ◽  
Dendritic Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Follicular Dendritic Cell ◽  
Large B Cell Lymphoma ◽  
Follicular Dendritic ◽  
Large B Cell

In this report, we describe a 38-year-old male with a very rare type of lymphoma, large B cell lymphoma with T cell-rich background and nodules lacking follicular dendritic cell meshworks (THRLBCL). In 2016 the patient presented hot flashes and night sweats (B-symptoms) and peripheral edema. He was treated with R-CHOP (doxorubicin, vincristine, cyclophosphamide, rituximab and Prednisone) chemotherapy, a Positron emission tomography–computed tomography (PET-CT) scan was performed after four cycles of treatment which showed radiologic complete response and blood test (complete blood count (CBC)) results showed normal ranges. As of September, 2020 he patient remains in complete remission. We searched the literature for descriptions of cases spanning the diagnostic spectrum of THRLBCL and we identified only five cases worldwide. The last reported case was in 2014 with distinctive features that were difficult to classify according to the World Health Organization criteria or previously described variants. Our patient is the sixth case of THRLBCL to be reported. He is the youngest of the reported cases and the first from Israel and the Middle East.

scholarly journals Clinical efficacy and molecular biomarkers in a phase II study of tucidinostat plus R-CHOP in elderly patients with newly diagnosed diffuse large B-cell lymphoma

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Mu-Chen Zhang ◽  
Ying Fang ◽  
Li Wang ◽  
Shu Cheng ◽  
Di Fu ◽  
...  
Keyword(s):  
Elderly Patients ◽  
B Cell ◽  
Response Rate ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Molecular Biomarkers ◽  
Newly Diagnosed ◽  
Large B Cell Lymphoma ◽  
Grade 3 ◽  
Large B Cell

Abstract Background Elderly patients with diffuse large B-cell lymphoma (DLBCL) present with poor clinical outcome and intolerance to intensive chemotherapy. Histone deacetylase inhibitors (HDACIs) show anti-lymphoma activities and can be applied to treat DLBCL. This study aimed to evaluate efficacy and safety of oral HDACI tucidinostat (formerly known as chidamide) plus R-CHOP (CR-CHOP) in elderly patients with newly diagnosed DLBCL (International Prognostic Index ≥ 2). Results Among 49 patients, the complete response rate was 86%, with overall response rate achieving 94%. The 2-year progression survival (PFS) and overall survival (OS) rates were 68% (95% CI 52–79) and 83% (95% CI 68–91). Comparing with historical control (NCT01852435), the 2-year PFS and OS rates of double-expressor lymphoma phenotype (DEL) were improved, and negative prognostic effect of histone acetyltransferases CREBBP/EP300 mutations was also mitigated by CR-CHOP. Grade 3–4 neutropenia was reported in 171, grade 3–4 thrombocytopenia in 27, and grade 3 anemia in 11 of 283 cycles. No grade 4 non-hematological adverse event was reported. Conclusion CR-CHOP is effective and safe in elderly patients with newly diagnosed DLBCL. Relevance of DEL phenotype and molecular biomarkers on CR-CHOP response warrants further investigation in DLBCL. Trial registration ClinicalTrial.gov, NCT02753647. Registered on April 28, 2016.

Primary Refractory Double Hit Diffuse Large B Cell Lymphoma: Complete Response with Ibrutinib and Rituximab

2018 ◽  
Vol 18 ◽  
pp. S294 ◽  
Author(s):  
Arnav Sethi ◽  
G. Obi ◽  
A. Manhas ◽  
A. Scholoff ◽  
N. Vu ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Large B Cell Lymphoma ◽  
Double Hit ◽  
Large B Cell

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

Blood ◽  
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.

The Efficacy of R-ICE Therapy as a Salvage Treatment for Relapse and Refractory Diffuse Large B-Cell Lymphoma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4441-4441
Author(s):  
Makoto Kodaira ◽  
Masahiro Yokoyama ◽  
Hiroaki Asai ◽  
Shuhei Yamada ◽  
Kyoko Ueda ◽  
...  
Keyword(s):  
B Cell ◽  
De Novo ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Salvage Chemotherapy ◽  
Salvage Treatment ◽  
Large B Cell Lymphoma ◽  
Grade 3 ◽  
Large B Cell

Abstract <Background> Patients with relapsed and refractory diffuse large B-cell lymphoma are usually treated with platinum-based salvage chemotherapy. We retrospectively analyzed the efficacy of adding rituximab with ICE as a salvage treatment for relapsed and refractory diffuse large B-cell lymphoma. <Method>From November 2003 to December 2006, patients with relapsed or refractory de novo diffuse large B-cell lymphoma represented CD20 positivty who received R-ICE (rituximab375mg/m2, Ifosfamide 1200mg/m2, calboplatin 400mg/m2 and etopside100mg/m2 ), were analyzed retrospectively. <Result>23 patients (19 relapse and 4 reflactory) (M:F=14:9) (median age 69, 28–77) were included. At starting treatment, twelve patients received rituximab and 11 patients were rituximab naive. In all 23 patients, responses were 11 Complete remission (CR), and 6 partial response (PR), resulting in overall response (ORR) was 74.9%. With median follow up of 10.5 months, estimated 1yr-progression free survival (PFS) was 49% and 1yr-overall survival (OS) was 70%.In patients received rituximab, ORR was 66.7% and 5 patiets achieved CR (41.7%).In the without rituximab, ORR was 90.9% and 7 patiets achieved CR (63.6%). No statistical differences were observed in response even with retuximab pretreatment. Estimated 1yr-PFS was 23% and 70% (p=0.0752) and 1yr-OS was 59% and83% (P=0.0049),respectively. NCI-CTC grade 3/4 neutropenia and thrombocytopenia were reported 100% and 91%, For non-hematological adverse event, there were grade 3 liver dysfunction (2/23) and grade 3 arrythmia (1/23). No toxic death was reported in this study. <Conclusion> R-ICE showed promising efficacy with tolelable toxicity. Available date suggested adding rituximab to ICE is more effective for patients not received rituximab in the pretreament.

Clinical Outcome and Survival of EBV-Positive Diffuse Large B-Cell Lymphoma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 5005-5005
Author(s):  
Brady Beltran ◽  
Pilar Quinones ◽  
Domingo Morales ◽  
Alex Capellino ◽  
Roberto Miranda ◽  
...  
Keyword(s):  
Risk Factors ◽  
B Cell ◽  
Median Survival ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Large B Cell Lymphoma ◽  
Extranodal Disease ◽  
Large B Cell

Abstract Abstract 5005 Background EBV-positive diffuse large B-cell lymphoma (DLBCL) is a new entity included provisionally in the most recent WHO Classification of lymphoid neoplasms. It usually affects elderly patients and has a poor survival. The goal of this study was to evaluate clinical characteristics and survival of EBV-positive DLBCL. Methods Between January 2002 and June 2008, twenty patients with EBV-positive DLBCL were deemed eligible for the study. Of those, eighteen cases were evaluable. All cases were positive for the presence of EBV-encoded RNA (EBER) by in situ hybridization, and CD20 and/or Pax-5 expression by immunohistochemistry (IHC). Clinical data were reviewed retrospectively and patient's biopsies were analyzed for the expression of bcl-6, CD10, CD30 and MUM-1 by IHC. The survival estimates were calculated using the Kaplan-Meier method and the log-rank test was used to compare the survival curves. Results The mean age was 72.7 years (range 34-95 years). B symptoms occurred in 6 patients (33%). Four patients (22%) presented with stage I, 4 (22%) with stage II, 5 (28%) with stage III and five (28%) with stage IV. The IPI risk score was low in 6 patients (33%), low intermediate in 2 (11%), high intermediate in 6 (33%) and high in 4 (22%). Extranodal disease occurred in 10 patients (55%); the most common extranodal sites were gastrointestinal tract (n=5), lung (n=3), suprarenal gland (n=1), bone (n=1), skin (n=1), tonsils (n=1) and bone marrow (n=1). Of 13 evaluated cases, eleven cases (83%) were of non-germinal center and 2 cases (17%) were of germinal center subtype. According to the Oyama score, 3 cases (17%) had 0 risk factors, 11 patients (61%) had 1 risk factor and 4 (22%) had 2 risk factors with median survival of 41, 11 and 1.5 months, respectively. Eight patients (44%) did not receive chemotherapy because they had a poor performance status. Ten patients (56%) received chemotherapy, eight received CHOP and two received R-CHOP. Overall response was 70% with a complete response in 7 cases and progressive disease in 3. No patients exhibited a partial response. Median survival for the entire group was 10 months; the median survival for the treated group was 17 months while for the untreated group was 2.5 months. The 2 patients treated with R-CHOP obtained a complete response. Conclusions EBV-positive DLBCL is an aggressive entity with frequent extranodal disease and a poor prognosis. The latter appears to be due to high IPI scores, non-germinal center immunophenotype and/or the presence of EBV. Although, EBV-positive DLBCL seems to respond well to R-CHOP, the survival remains dismal. Prospective studies are needed to validate EBV's prognostic, predictive and therapeutic value in DLBCL in the post-rituximab era. Disclosures No relevant conflicts of interest to declare.

Circulating tumor DNA assessment in patients with diffuse large B-cell lymphoma following CAR-T therapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 7552-7552 ◽  
Author(s):  
Saurabh Dahiya ◽  
Ryan Le ◽  
Nasheed Mohammad Hossain ◽  
Matthew Abramian ◽  
Lori S. Muffly ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Pcr Amplification ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Circulating Tumor Dna ◽  
Large B Cell Lymphoma ◽  
Car T ◽  
Tumor Dna ◽  
Large B Cell

7552 Background: Circulating tumor DNA(CTD) have been used for disease monitoring in Diffuse Large B Cell Lymphoma(DLBCL) (Kurtz ASCO 2016). Role of CTD assessment in DLBCL patients treated with CAR-T therapy has not been studied. We prospectively analyzed CTD of dynamics measured by next generation sequencing(NGS) of BCR using ClonoSeq MRD(Adaptive Biotechnologies), before and after CAR-T therapy to determine feasibility and clinical utility. Methods: At Stanford, 7 patients were enrolled on ZUMA-1 clinical trial NCT02348216, treating chemo-refractory DLBCL patients with anti-CD19, CAR-T. Complete radiologic data and CTD analysis was collected for six subjects. Tumor-DNA was extracted from archival paraffin-embeded tissue & analyzed using the NGS-based assay. PCR amplification of IGH-VDJ, IGH-DJ & IGK regions using universal consensus primers was performed followed by NGS to determine the tumor clonotype(s). Blood collected at day 0,7,14,28,60 & 90 days in relation to CAR-T infusion was used to detect CTD by ClonoSeq quantification of clonotypes. Results: Clonotypes were successfully determined for all 6 subjects, and 30 blood samples for 6 patients were prospectively analyzed. All patients had measurable disease burden pre-CAR-T infusion. CTD dynamics correlated with PET-CT outcomes in 100% of the patients. Increasing CTD temporally preceded progressive disease(PD) before PETCT recognition in 4 of 5 patients and was always increasing when PETCT showed PD. Preceding CTD quantification correlated with disease volume increase. One patient achieved durable KTE-19 complete response(CR) and detectable CTD became undetectable on day 14(and on subsequent samples) following CAR-T infusion, corresponding to 1 & 3 month PETCT CR. Additionally, the burden of disease measured by lymphoma molecules per ml allowed volumetric response assessment in all the patients who experienced massive reduction in tumor volume, but by traditional response definition had partial response. Conclusions: ClonoSeq CTD provides precise total tumor quantification of DLBCL in the CAR-T cell setting. This technology may overcome fundamental limitations of DLBCL imaging(cost, radiation exposure & limited repetition).

Comparison of salvage therapies for relapsed or refractory diffuse large B-cell lymphoma (DLBCL): Network meta-analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e19037-e19037 ◽  
Author(s):  
Venkata Vosuri ◽  
Ravi Kaisreddy ◽  
Somasekhar Bandi
Keyword(s):  
Adverse Events ◽  
B Cell ◽  
Cell Lymphoma ◽  
Meta Analysis ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
High Dose ◽  
Large B Cell Lymphoma ◽  
High Dose Cytarabine ◽  
Large B Cell

e19037 Background: Salvage chemotherapy followed by autologous stem cell transplantation(ASCT) is the standard second-line treatment for relapsed or refractory diffuse large b-cell lymphoma(DLBCL). Rituximab plus ifosfamide, carboplatin, and etoposide(R-ICE) and rituximab plus dexamethasone, high dose cytarabine, cisplatin(R-DHAP) are the two widely used regimens worldwide but quest for optimal regimen continues. Our objective is to compare currently available salvage therapies based on complete response and adverse events. Methods: Pubmed, EMBASE and Clinicaltrials.gov were queried for salvage therapies in relapsed or refractory DLBCL. Only randomized clinical trials including phase 2 and 3 trials involving salvage therapies for relapsed or refractory DLBCL were selected. Data was extracted based on meta-analysis guidelines by two independent reviewers. Network meta-analyses of treatment effects and adverse outcomes were calculated with a frequentist approach. Results: Overall, 5 studies(1480 patients) were included. The salvage therapies investigated were rituximab plus ifosfamide, carboplatin, and etoposide(R-ICE), rituximab plus dexamethasone, high dose cytarabine, cisplatin(R-DHAP), rituximab plus gemcitabine, dexamethasone, cisplatin(R-GDP), ofatumumab plus dexamethasone, cytarabine, and cisplatin(O-DHAP), ifosfamide plus ofatumunab, carboplatin, and etoposide(O-ICE), dacetuzumab plus rituximab, ifosfamide, carboplatin and etoposide(DR-ICE). Of the 6 regimens in the network, treatment with R-DHAP (OR:0.36,95%CI:0.24-0.54), R-GDP(OR:0.37,95%CI: 0.21-0.65), O-ICE(OR:0.16,95%CI: 0.05-0.53), O-DHAP(OR:0.30,95%CI:0.17-0.52), DR-ICE(OR:0.77,95%CI:0.40-1.49) were not superior against network placebo(R-ICE) in achieving complete response. Higher odds of occurring severe adverse events was observed in R-DHAP(OR:2.02,95%CI: 1.35-3.01) and O-DHAP(OR:2.15,95%CI: 1.24-3.72) salvage regimens when compared to R-ICE. Conclusions: R-DHAP, R-GDP, O-ICE and O-DHAP were found to have no difference in treatment effect in achieving complete response in comparison to R-ICE. R-DHAP and O-DHAP are associated with higher number of severe adverse events in comparison with R-ICE. Outcomes mentioned above should be interpreted in the context of drugs and other factors involved in the disease.

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