Ruxolitinib for the treatment of lymphoma-associated hemophagocytic lymphohistiocytosis: A cautionary tale

2019 ◽  
Vol 26 (4) ◽  
pp. 1005-1008 ◽  
Author(s):  
Tanner Trantham ◽  
Jessica Auten ◽  
Benyam Muluneh ◽  
Hendrik Van Deventer

Introduction Hemophagocytic lymphohistiocytosis is a hyperinflammatory syndrome characterized by fever, hyperferritinemia, hypertriglyceridemia, hypofibrinogenemia, and pancytopenia. Three publications reported success with ruxolitinib, a Janus-associated kinase (JAK1/2) inhibitor. This therapy interrupts the production of cytokines associated with hemophagocytic lymphohistiocytosis, namely interferon-γ and interleukins 2, 6, and 10. Case report We administered ruxolitinib to two patients with lymphoma-associated hemophagocytic lymphohistiocytosis who had failed standard treatment with dexamethasone and etoposide. Management and outcome Patient #1 was started on ruxolitinib 10 mg BID, and titrated to 15 mg BID. All but two of the hemophagocytic lymphohistiocytosis criteria resolved within two weeks, and she was able to restart therapy for lymphoma. During her ruxolitinib taper, she again presented with relapsed hemophagocytic lymphohistiocytosis. She was taking 2.5 mg a day at the time. Despite salvage treatment, she died from the disease. Patient #2 was a diffuse large B-cell lymphoma patient who presented with hemophagocytic lymphohistiocytosis and was treated with chemoimmunotherapy and achieved a complete response (CR). Hemophagocytic lymphohistiocytosis symptoms relapsed, and he was treated with ruxolitinib. He developed relapsed lymphoma and unfortunately died. Discussion While treating the underlying lymphoma is a clear priority, the cytopenias and other symptoms of hemophagocytic lymphohistiocytosis complicate the delivery of this therapy. Hence, the use of ruxolitinib as a bridge to definitive therapy was appealing. However, we are concerned about the progression of lymphoma while these patients were taking ruxolitinib. Ruxolitinib may be controlling cytokine storm associated with hemophagocytic lymphohistiocytosis, while other aspects of the condition are progressing. Therefore, we would advise caution in its use in lymphoma-associated-hemophagocytic lymphohistiocytosis until more data are available.

Author(s):  
Walid Shalata ◽  
Ismaell Massalha ◽  
Kayed Al-Athamen

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.


2016 ◽  
Vol 146 (suppl_1) ◽  
Author(s):  
Asa Rubin ◽  
Laura Biederman ◽  
Upasana Joneja ◽  
Dimath Alyemni ◽  
Jerald Gong ◽  
...  

2014 ◽  
Vol 56 (5) ◽  
pp. 1521-1523 ◽  
Author(s):  
Vahid Entezari ◽  
Eberechi Agwa ◽  
Sory J. Ruiz ◽  
Steven A. Lietman ◽  
Bernard J. Silver ◽  
...  

2018 ◽  
Vol 18 ◽  
pp. S294 ◽  
Author(s):  
Arnav Sethi ◽  
G. Obi ◽  
A. Manhas ◽  
A. Scholoff ◽  
N. Vu ◽  
...  

Author(s):  
Adrienne A. Phillips ◽  
Dominic A. Smith

Lymphoma encompass a wide variety of distinct disease entities, including, but not limited to, subtypes of non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL). In the last 3 decades, therapeutic advancements have resulted in substantial improvements in lymphoma outcome. In most high-income regions, HL is a largely curable disease and for patients with two frequent subtypes of NHL, diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL), survival has dramatically improved with the incorporation of rituximab as a standard treatment approach. Despite these advances, outcomes vary between and across populations. This review will provide updated information about health disparities in lymphoma in the United States and across the globe.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 5005-5005
Author(s):  
Brady Beltran ◽  
Pilar Quinones ◽  
Domingo Morales ◽  
Alex Capellino ◽  
Roberto Miranda ◽  
...  

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.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4421-4421
Author(s):  
Ji Hyun Park ◽  
Dok Hyun Yoon ◽  
Shin Kim ◽  
Jung Sun Park ◽  
Sang-wook Lee ◽  
...  

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


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 7552-7552 ◽  
Author(s):  
Saurabh Dahiya ◽  
Ryan Le ◽  
Nasheed Mohammad Hossain ◽  
Matthew Abramian ◽  
Lori S. Muffly ◽  
...  

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).


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