Complete response to pixantrone as a salvage therapy in a relapsed/refractory diffuse large B-cell lymphoma

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.

Download Full-text

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

Clinical Lymphoma Myeloma & Leukemia ◽

10.1016/j.clml.2018.07.239 ◽

2018 ◽

Vol 18 ◽

pp. S294 ◽

Cited By ~ 1

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

Download Full-text

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

Blood ◽

10.1182/blood.v114.22.5005.5005 ◽

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.

Download Full-text

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

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.7552 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 7552-7552 ◽

Cited By ~ 1

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).

Download Full-text

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

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e19037 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e19037-e19037 ◽

Cited By ~ 1

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.

Download Full-text

Final results of a phase II trial of R-IDEA as salvage therapy in patients with relapsed/refractory diffuse large B-cell lymphoma

Annals of Oncology ◽

10.1093/annonc/mdw375.26 ◽

2016 ◽

Vol 27 ◽

pp. vi321

Author(s):

E. Kondo ◽

K. Yamamoto ◽

T. Masunari ◽

J. Takizawa ◽

K. Miura ◽

...

Keyword(s):

B Cell ◽

Phase Ii ◽

Salvage Therapy ◽

Phase Ii Trial ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Large B Cell Lymphoma ◽

Large B Cell

Download Full-text

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

Acta Haematologica ◽

10.1159/000368291 ◽

2015 ◽

Vol 133 (4) ◽

pp. 347-353 ◽

Cited By ~ 4

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.

Download Full-text