278. Immunocompromised Patients with Prolonged Viral Shedding of SARS-COV-2

Abstract Background Most individuals diagnosed with mild to moderate COVID-19 are no longer infectious after day 10 of symptom onset and those with severe or critical illness from COVID are typically not infection after day 20 day of symptom onset. Recovered persons can continue to test positive for SARS-CoV-2 by PCR via detection of non-viable RNA in nasopharyngeal specimens for up to three months (or longer) after illness onset. It is also know known that severely immunocompromised patients may produce replication-competent virus greater than 20 days from symptom onset and may require, per CDC recommendations, “additional testing and consultation with infectious diseases specialists and infection control experts”. We aim to discuss four case studies of severely immunocompromised patients who exhibited signs of persistent COVID-19 infection of COVID and how we managed transmission-based precautions in our hospital through sequencing and evaluation of cycle thresholds (CT) values and subgenomic RNA detection. Methods Residual nasopharyngeal (NP) samples were collected on patients exhibiting persistent COVID like symptoms. These samples underwent N gene and N gene subgenomic RNA (sgRNA) real-time reverse transcription polymerase chain reaction (rRT-PCR) testing. Results Analysis of longitudinal SARS-CoV-2 sequence data demonstrated within-patient virus evolution, including mutations in the receptor binding domain and deletions in the N-terminal domain of the spike protein, which have been implicated in antibody escape. See Figures 1 and 2. Figure 1. Timelines of Identified Patients 1 and 2 Patient 1: 46-year-old woman with recently diagnosed stage IV diffuse large B-cell lymphoma for which she was treated with 2 cycles of R-CHOP. Patient 2: 38-year-old woman with history of myelodysplastic syndrome, peripheral blood stem cell transplant with chronic graft versus host disease of the GI tract, skin, and eyes as well as CMV enteritis, and she was maintained on rituximab, mycophenolate mofetil, prednisone, and monthly IVIG without recent changes to her immunosuppression. Figure 2. Timeline of Identified Patients 3 and 4 Patient 3: 44 year-old man with prior history of thymoma s/p thymectomy Patient 4: 46 year-old man who was initially diagnosed with marginal zone lymphoma approximately 2.5 years ago. He was initially treated with bendamustine and rituximab and achieved remission. He was then continued on maintenance rituximab without significant complications for a planned two years. Conclusion Differentiating between prolonged viral shedding of non-infectious RNA and persistent replicating viable virus can be difficult to determine without full evaluation of a patient’s clinical picture and timeline. Consultation between laboratory, infectious diseases, and infection prevention experts to provide appropriate level of guidance for precautions and treatment may be warranted. Testing by PCR and analysis of CT values may provide key findings of viral replication in immunocompromised hosts, indicating the need for evaluation of additional treatment and maintaining isolation status in healthcare settings. Disclosures All Authors: No reported disclosures

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Real world treatment patterns in chronic myeloid leukemia patients newly initiated on tyrosine kinase inhibitors in an U.S. integrated healthcare system

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155217697484 ◽

2017 ◽

Vol 24 (4) ◽

pp. 253-263

Author(s):

Nazia Rashid ◽

Han A Koh ◽

Kathy J Lin ◽

Brian Stwalley ◽

Eugene Felber

Keyword(s):

Chronic Myelogenous Leukemia ◽

Index Date ◽

Stem Cell Transplant ◽

Study Time ◽

Myelogenous Leukemia ◽

Prior History ◽

Cell Transplant ◽

Time Period ◽

History Of

Purpose To evaluate treatment patterns in patients diagnosed with incident chronic myelogenous leukemia (CML) newly initiating therapy with imatinib, dasatinib, or nilotinib. Patients were followed to determine switching and discontinuation rates. Factors associated with switching or discontinuation from index TKI therapy, reasons for discontinuation based on electronic chart notes, and frequency of laboratory monitoring were assessed during the follow-up period. Methods A retrospective cohort study was conducted in chronic myelogenous leukemia patients aged ≥ 18 years who were identified from the Kaiser Permanente Southern California (KPSC) Cancer Registry database during the study time period of 1 January 2007 to 12 December 2013. The index date was defined as the date of the first TKI prescription (imatinib, dasatinib, or nilotinib) identified during the study time period with no prior history of TKI use within 12 months. Patients had to have continuous membership with drug benefit eligibility and no prior history of stem cell transplant (SCT) or other cancers during the 12 months prior to the index date. Baseline characteristics were identified during 12 months prior to the index date and outcomes were identified during the follow-up period after the index date. All patients were followed from index TKI therapy until end of study time period (12 December 2014), death, stem cell transplant, or disenrollment from the health plan unless one of the following occurred first: a patient switched their index therapy, or a patient discontinued their index therapy. Forward stepwise selection multivariable logistic regression models were used to evaluate factors associated with patients who continued therapy compared to those who switched or discontinued therapy with the index TKI. Chart notes were reviewed 30 days prior and 30 days post index TKI discontinuation to evaluate reasons for discontinuation. Molecular and cytogenetic testing frequency was also assessed during the follow-up period among the different patient groups. Results Two hundred sixteen patients were identified with incident chronic myelogenous leukemia and use of TKI therapy: 189 (87.5%) received imatinib, 19 (8.8%) received dasatinib, and 8 (3.7%) received nilotinib. The mean age on index date was 53 years and 63% were male; 103 patients (48%) continued on their index therapy, while 62 patients (28%) switched, and 51 patients (24%) discontinued.

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Management of Hodgkin Lymphoma in Relapse after Autologous Stem Cell Transplant

Hematology ◽

10.1182/asheducation-2008.1.326 ◽

2008 ◽

Vol 2008 (1) ◽

pp. 326-333 ◽

Cited By ~ 37

Author(s):

Michael Crump

Keyword(s):

Stem Cell ◽

Hodgkin Lymphoma ◽

Treatment Algorithm ◽

Allogeneic Transplantation ◽

Autologous Stem Cell Transplant ◽

Disease Stage ◽

Prior History ◽

Cell Transplant ◽

History Of ◽

Multiagent Chemotherapy

AbstractRecurrence of Hodgkin lymphoma (HL) occurs in about 50% of patients after autologous stem cell transplantation (ASCT), usually within the first year, and represents a significant therapeutic challenge. The natural history of recurrent HL in this setting may range from a rapidly progressive to a more indolent course. Patients in this setting are often young, without comorbidities and able to tolerate additional therapies: expectations are often still high. The approach to treatment depends on clinical variables (time to relapse, perceived sensitivity to additional cytotoxic therapy, disease stage), prior history of radiation therapy, the availability of an HLA-identical donor, and the availability of new agents via clinical trials. Although very few of these patients can be cured, results from reported series, albeit often small and sometimes with relatively short follow-up, document that excellent disease control can be achieved with radiation, single or multiagent chemotherapy, and reduced-intensity allogeneic transplantation. The results of these approaches will be reviewed, and a treatment algorithm incorporating the use of standard or investigational agents or approaches will be discussed.

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B Cell Lymphoma In Association with Multiple Myeloma: Analysis of the Biologic Relationship

Blood ◽

10.1182/blood.v118.21.1590.1590 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1590-1590 ◽

Cited By ~ 3

Author(s):

Anuj K. Mahindra ◽

Aliyah R. Sohani ◽

Christiana E. Toomey ◽

James S. Michaelson ◽

Jeffrey A. Barnes ◽

...

Keyword(s):

Multiple Myeloma ◽

B Cell ◽

Board Of Directors ◽

Light Chain ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Prior History ◽

Advisory Committees ◽

Age Of Diagnosis ◽

History Of

Abstract Abstract 1590 Background: The occurrence of a secondary lymphoma in patients with a prior history of B-cell lymphomas has been reported.1, 2 There are few reported occurrences of Multiple Myeloma (MM) in patients (pts) with a prior history of lymphoma and the biologic relationship between the two neoplasms in such cases is unknown. Methods: We queried our IRB approved clinicopathologic database of hematologic malignancies for patients with lymphoma and MM. Of the 4165 pts with B-cell lymphoma and 804 pts with MM, 6 pts with a history of B-cell lymphoma developed MM and 1 patient with a prior history of MM developed a B-cell lymphoma. We describe the morphology, immunophenotype, and clinical features of the 7 pts. The clonal relationship of the 2 components was analyzed using sequencing analysis of immunoglobulin heavy chain variable region (IgVH) genes and by light chain restriction. Results: There were 5 men and 2 women (median age of diagnosis of lymphoma, 65 years; median age of diagnosis of MM, 71 years). The pts with lymphoma included 2 pts with diffuse large B cell lymphoma, 2 pts with small lymphocytic lymphoma, 2 pts with follicular lymphoma and 1 patient with lymphoplasmacytic lymphoma. The development of MM was metachronous in 5 cases, following B-cell lymphoma by 3 years to 23 years and synchronous in 1 case. In 1 patient, the B-cell lymphoma developed 6 years after the diagnosis of MM. 6 pts achieved complete remission after treatment for lymphoma and 1 patient is ongoing treatment. 6 of the 7 pts required treatment for MM soon after diagnosis. 1 patient has smoldering MM and continues to be observed 57 months after diagnosis. FISH analysis indicated IgH rearrangement in 3 pts with MM; 1 patient with 17p deletion and monosomy 13; 3 pts had normal FISH and metaphase cytogenetics. In 3 pts, both neoplasms were kappa light chain restricted; in 1 patient both were lambda restricted; in 1 patient, the lymphoma was lambda light chain restricted while the MM was kappa light chain restricted and the reverse in another pt; in 1 patient the B-cell lymphoma was light chain negative and the MM was kappa restricted. IgVH rearrangement studies in 4 patients in whom tissue samples were available indicated that the two were clonally unrelated in 3 patients and related in only 1 patient. Conclusion: Clonality analysis of rearranged immunoglobulin genes from patients with both B-cell lymphoma and MM provide evidence of separate clonal origins of the two tumors in the majority of cases, thus excluding secondary transformation of the original B-cell clone. The presence or absence of a genetic predisposition to the development of multiple B cell malignancies requires further study.3 Disclosures: Off Label Use: The combination of lenalidomide and everolimue is an off label use in multiple myeloma. Abramson:Genentech: Consultancy; Novartis: Consultancy. Raje:Amgen: Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Research Funding; Millenium: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Acetylon: Research Funding.

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ASXL1/SRSF2 Co-Mutated Acute Myeloid Leukemia (AML): A Rare but Distinct Subpopulation with Dismal Outcomes

Blood ◽

10.1182/blood-2019-122929 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2598-2598

Author(s):

Daniel R. Richardson ◽

David M Swoboda ◽

Anastasia Ivanova ◽

Steven M Johnson ◽

Jonathan Galeotti ◽

...

Keyword(s):

Research Funding ◽

Multivariable Analysis ◽

Prior History ◽

Treatment Intensity ◽

Cell Transplant ◽

Myeloid Neoplasm ◽

Significant Difference ◽

History Of ◽

Baseline Characteristics

Background: Advances in the understanding of the genetic determinants of AML and the widespread use of next-generation sequencing (NGS) have led to the refinement of prognostically distinct molecular subgroups. Mutations in ASXL1 and SRSF2, which are common in myelodysplastic syndrome (MDS) and myeloproliferative neoplasms (MPNs), rarely co-occur in patients (pts) with AML. The largest reported cohort (n=15) of ASXL1/SRSF2 co-mutated AML had no long-term survivors (Papaemmanuil et al. NEJM 2016). It remains unknown how clinical factors such as prior history of a myeloid neoplasm or intensity of treatment influence outcomes. We sought to assess the clinical characteristics and analyze outcomes in a larger cohort of pts with ASXL1/SRSF2 co-mutated AML. We hypothesized that this profile may be a genomic footprint of prior myeloid neoplasia. Methods: We conducted a multi-institutional retrospective analysis of newly diagnosed adult AML pts with both ASXL1 and SRSF2 mutations at the University of North Carolina and at Moffitt Cancer Center from 2011-2018. NGS was performed on DNA using the Illumina TruSight Myeloid 54-gene sequencing panel. The primary endpoint was overall survival (OS) defined as time from diagnosis of AML to death. Pts were stratified by secondary AML (s-AML), defined as having a documented history of MDS/MPN. Secondary outcomes included rates of complete remission (CR) and CR with incomplete hematologic recovery (CRi). Multivariable analysis was performed with baseline characteristics. Results: Forty-six pts were identified and included. The median age of pts was 72 years (range 42 - 85). Sixty-seven percent (28/42) had normal cytogenetics; 88% (37/42) were intermediate risk cytogenetics by current ELN guidelines. Sixty-one percent (n=28) were classified as having s-AML. One pt had therapy-related AML without preexisting MDS/MPN and was therefore not included in s-AML. The Figure illustrates co-existing mutations and individual responses to upfront therapy stratified by s-AML and non-s-AML. The median number of mutations was 5 (range 2 - 7). The most common co-occurring mutations were TET2 (52%), RUNX1 (35%), IDH2 (15%), and STAG2 (15%). Median OS was 7.0 months (m) (CI 5.3, 15.4). Median OS for pts with s-AML (n=28) and non-s-AML (n=18) was 6.1 and 15.4 m (p=0.05), respectively. There was no significant difference in median OS between s-AML and non-s-AML on multivariable analysis (hazard ratio (HR) = 2.56, p=0.07). Median OS did not differ by age (Age <65 years v. older, p=0.54), total # of mutations (≥ 5 v. less, p=0.73), or etiology of s-AML (MDS v. MPN, p=0.66). Twenty-two (47%) pts received upfront intensive induction chemotherapy (IC), 17 (37%) received hypomethylating agents (HMAs), and 7 pts (15%) received no AML-directed chemotherapy. Median OS did not significantly differ between pts receiving upfront IC and HMAs (15.3 v. 7.04 m, p=0.21). Among non-s-AML pts, median OS was longer in those receiving IC (n=10) versus HMAs (n=7) (15.4 v. 3.5 m, p=0.01). Among all pts receiving IC, median OS was longer in non-s-AML pts (n=10) versus s-AML pts (n=12) (15.4 v. 5.9 m, p=0.01). Median OS did not differ by treatment intensity for s-AML pts (IC v. HMA: 5.9 v. 9.9 m, p=0.38). Six pts underwent allogeneic hematopoietic cell transplant (HCT) with a median OS NR (median follow-up 15.6 m). Overall rate of CR/CRi was 35% and was similar between pts receiving IC and HMAs (45% v. 21%, p=0.29). Among pts with non-s-AML, CR/CRi rates with IC and HMAs were 70% and 29%, respectively (p=0.11). Among pts with s-AML, CR/CRi rates with IC and HMAs were 42% and 20%, respectively (p=0.38). On multivariable analysis of baseline characteristics, only ECOG performance status (PS) was significantly associated with OS (HR 2.25, p=0.01). ECOG PS remained significant (HR 2.65, p=0.03) after adjusting for HCT and treatment intensity. Conclusions: ASXL1/SRSF2 co-mutated AML represents a rare but distinct genotype with most pts having pre-existing myeloid neoplasms and associated co-mutations commonly seen in MDS/MPNs. OS is dismal regardless of age, number of mutations, treatment intensity, or prior history of myeloid neoplasm. HCT may mitigate these poor outcomes and lead to long-term survival. This represents the largest reported cohort to date of pts with ASXL1/SRSF2 co-mutated AML. Further study is warranted to inform risk stratification and prognosis of pts with ASXL1/SRSF2-mutated AML. Disclosures Foster: Bellicum Pharmaceuticals, Inc: Research Funding; Daiichi Sankyo: Consultancy; MacroGenics: Research Funding; Celgene: Research Funding. Coombs:Octopharma: Honoraria; Pharmacyclics: Honoraria; Medscape: Honoraria; Abbvie: Consultancy; Loxo: Honoraria; Cowen & Co.: Consultancy; Dedham Group: Consultancy; H3 Biomedicine: Honoraria; Covance: Consultancy. Sallman:Celyad: Membership on an entity's Board of Directors or advisory committees. Zeidner:Agios: Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Honoraria; Tolero: Honoraria, Research Funding; Pfizer: Honoraria; AsystBio Laboratories: Consultancy; Merck: Research Funding; Takeda: Research Funding; AbbVie: Honoraria.

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2789. Respiratory Syncytial Disease in Hospitalized Adults: A Retrospective Cohort Study

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.2466 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S985-S986

Author(s):

Hannah Nam ◽

Michael G Ison

Keyword(s):

Mechanical Ventilation ◽

Cohort Study ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Severe Disease ◽

Solid Organ ◽

Cell Transplant ◽

Immunocompromised Patients ◽

Transplant Patients ◽

History Of

Abstract Background Respiratory syncytial virus (RSV) is associated with significant mortality rates amongst hematopoietic stem cell transplant (HSCT) and lung transplant recipients. Although RSV is responsible for ~177,000 hospitalizations and 14,000 deaths annually, few epidemiologic studies including all adults including those with immunocompromise have been conducted over multiple seasons. Methods A retrospective cohort study of adults admitted to a large academic medical center in Chicago, IL from 2009 to 2018 was conducted in patients with positive RSV PCR. Specific data on clinical presentation, management, and outcomes were collected by manual chart review. Descriptive statistics were calculated, and Pearson’s Chi-Squared test was utilized to assess association between severe disease status and comorbidities. Results A total of 140 patients* were admitted during part of the study period (2016–2018) with positive PCR for RSV. Most patients had otherwise underlying comorbidities prior to admission (lung 44.2%, heart 40.0%, diabetes 20.7%), history of immunocompromise (36.4%, 51) or history of smoking (39.2%, 55). Cough was the most common symptom among all hospitalized adults (90.7%, 127). However, patients with a history of transplant (both HSCT and SOT) more commonly displayed symptoms of fevers at presentation (50%, 10) when compared with non-immunocompromised patients (36.6%, 36). ICU admission occurred in one-third of the hospitalized patients, with no significant difference amongst transplant patients, immunocompromised patients, and non-immunocompromised patients. Need for mechanical ventilation was highest in patients with co-infections. None of the co-morbidities measured were independent risk factors for severe disease. Most patients (78.5%, 110) were discharged home. Among the 12 fatal cases, all were admitted to the ICU with seven (58.3%) requiring mechanical ventilation. Three (25.0%) were immunocompromised while two (16.7%) were HSCT patients, but none were solid-organ transplant patients. *Ongoing data collection. Conclusion RSV patients were diverse in their demographics, treatment, and outcomes. Large percentages of patients had underlying comorbidities such as immunocompromise due to HSCT, lung and heart disease. Disclosures All authors: No reported disclosures.

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Single-Agent Lenalidomide for Patients with Relapsed/Refractory Aggressive Non-Hodgkin's Lymphoma Who Had Received Prior Stem Cell Transplant.

Blood ◽

10.1182/blood.v114.22.2699.2699 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2699-2699

Author(s):

Julie M. Vose ◽

Thomas Habermann ◽

Myron S Czuczman ◽

Pier Luigi Zinzani ◽

Craig B. Reeder ◽

...

Keyword(s):

Stem Cell ◽

Research Funding ◽

Stem Cell Transplant ◽

Cell Lymphoma ◽

Prior History ◽

Cell Transplant ◽

Phase 2 ◽

Two Phase ◽

Phase Ii Studies ◽

History Of

Abstract Abstract 2699 Poster Board II-675 Introduction: High-dose chemotherapy with autologous stem cell transplant (SCT) is a standard treatment option for younger patients with aggressive non-Hodgkin's lymphomas (a-NHL) who fail to respond, or relapse after initial therapy. For patients who relapse after SCT there are few effective treatment options and prognosis remains poor (Vose et al Blood. 80(8):2142–8, 1992). A second SCT was shown to achieve only marginal responses and at an increased risk of toxic death (Lenain et al Hematol J. 5(5):403–9, 2004). Therefore, new approaches are needed for treatment of patients in this poor prognostic group. Lenalidomide (Revlimid®) is an immunomodulatory agent that has shown clinical activity in treatment of several B-cell malignancies. Two phase 2 studies of lenalidomide monotherapy in patients with relapsed or refractory (R/R) a-NHL were conducted in the US (NHL-002; Wiernik et al JCO 26:4952–7, 2008) and internationally (CC-5013 NHL-003). In an extended follow-up of the NHL-002 study, the overall response rate (ORR) was 35%, which included 12% of patients with a complete response (CR), and a median duration of response (DR) lasting 10.4 months (Wiernik et al 2008 EHA. Abst: 764). Comparable efficacy was observed in the larger confirmatory, phase 2, NHL-003 study of lenalidomide in a similar patient population. The goal of this analysis was to learn the ORR and DR to lenalidomide in patients with a prior SCT. Methods: Patient data from both phase II studies were pooled for this report. Eligibility for both studies was similar – patients with R/R a-NHL, which included diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), transformed lymphoma (TL), and follicular lymphoma grade III (FL-III), with measurable disease (≥ 2 cm), and ≥ 1 prior treatment regimen. Patients received oral lenalidomide 25 mg once daily on days 1–21 of a 28-day cycle. Protocol defined treatment continued for up to 52 wks in NHL-002, or until disease progression in NHL-003. Primary endpoint was ORR; secondary endpoints included DR, progression-free survival (PFS), and safety. Results: 87 patients with a prior SCT (14 patients from NHL-002; 73 patients from NHL-003) were included in this analysis. Median age of patients was 61 yrs (range, 23–76), with a median of 4 prior therapies (range, 2–12). The ORR to lenalidomide was 39% (34/87), with 13% (11/87) CR/CRu and 26% (23/87) partial response (PR). Median PFS for all 87 patients was 3.8 months (95% CI, 2.6, 5.6) and the DR for 34 responders was 9.7 months (95% CI, 4.2, 16.3). Responses occurred in 15 of 52 patients (29% ORR; 10% CR/CRu) with DLBCL, 12 of 19 patients with MCL (63% ORR; 26% CR/CRu), and in 6 of 10 patients with TL (60% ORR; 10% CR/CRu). The table summarizes responses for patients who did not have a transplant, for those who had a SCT anytime prior to lenalidomide; as the last therapy prior to lenalidomide; and not as last therapy prior to lenalidomide. Most common grade 3 or 4 adverse events were neutropenia (44%), thrombocytopenia (33%), and anemia (9%). Eighteen (20.6%) patients discontinued treatment due to adverse events. Patients with a prior history of SCT appeared to have a significantly higher rate of thrombocytopenia, all grades (51% v 30%; P = 0.001), and grades 3 or 4 (33% v 16%; P = 0.002). Patients with a prior SCT were also more likely to experience a dose reduction/interruption due to thrombocytopenia compared with those without a prior SCT (25% v 14%; P = 0.027). Conclusions: Based on a pooled dataset from two phase II studies, oral lenalidomide monotherapy appears to be a well tolerated and active therapy resulting in durable responses in patients with R/R a-NHL who had a prior SCT. Furthermore, the potential of achieving a response to lenalidomide appears to be independent of prior history of SCT. Disclosures: Vose: Celgene: Research Funding. Off Label Use: Lenalidomide for the treatment of relapsed/refractory aggressive non-Hodgkin's lymphoma. . Czuczman:Celgene: Research Funding. Zinzani:Celgene: Research Funding. Tuscano:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Pietronigro:Celgene: Employment, Equity Ownership. Ervin-Haynes:Celgene: Employment. Witzig:Celgene: Research Funding.

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Natural History of Transformed Non-Hodgkin Lymphoma in the Rituximab Era: Analysis of the National Comprehensive Cancer Network (NCCN) NHL Outcomes Database.

Blood ◽

10.1182/blood.v120.21.2669.2669 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2669-2669

Author(s):

Makiko Ban-Hoefen ◽

Ann Vanderplas ◽

Jennifer L. Kelly ◽

Allison Crosby-Thompson ◽

Gregory A. Abel ◽

...

Keyword(s):

Natural History ◽

B Cell Lymphoma ◽

Outcome Data ◽

Treatment Modalities ◽

Cell Transplant ◽

Indolent Lymphoma ◽

Salvage Regimen ◽

Term Survival ◽

Historical Series ◽

History Of

Abstract Abstract 2669 Background The prognosis of histologic transformation (HT) of indolent non-Hodgkin's Lymphoma (NHL) in the pre-rituximab era has been dismal, with a median survival after HT of approximately one year. The natural history of HT in the rituximab era has not been previously described. Methods Using the National Cancer Comprehensive Network (NCCN) NHL database, a multicenter prospective registry of comprehensive clinical, treatment, and outcome data for patients (pts) with NHL, we evaluated the natural history of HT. All HT-NHL pts in participating NCCN centers between July 1, 2000-February 29, 2011, were eligible for inclusion in this cohort. Definition of transformation: (1) confirmed documentation of initial pathologic diagnosis of indolent disease, (2) biopsy proven transformation to Diffuse Large B-Cell Lymphoma (DLBCL) > 6 months from the initial diagnosis of the indolent histology. Results Clinical characteristics of pts at transformation (n=118): median age: 59; histology of indolent lymphoma: Follicular Lymphoma (FL) grades 1–2a: 86 (72%), FL grade 3 or 3a: 12 (10%), FL grade NOS: 4 (3%), other indolent NHL: 16 (13%). Treatment for the indolent lymphoma pre-HT: 83 (70%) treated with rituximab, 60 (51%) exposed to anthracyclines, and 23 (19%) observed without any treatment. Median number of one prior therapeutic line given prior to HT. Median time from indolent NHL to HT: 30 months (range: 6–184). Treatment modalities for HT included autologous stem-cell transplant (auto-SCT) (n=50), allogeneic SCT (allo-SCT) (n=18), and no transplant (n=50). For the non-transplanted pts, treatment for HT included chemotherapy (94%) at HT, of which an R-CHOP-based regimen was the most commonly used (56%). A salvage regimen (cytarabine- or platinum-based) was used in 19 (38%), a lenalidomide-based regimen was used in 2 (4%), and radioimmunotherapy was administered in 3 (6%). There were three (6%) patients who neither obtained transplantation nor any treatment for HT. Pts not transplanted were older than those transplanted (64 vs 57 years, p=0.002), and pts in the auto-SCT group were older compared to the allo-SCT group (60 vs 52 years, p<0.0001). A higher percentage of the transplanted pts had a history of being treated with chemotherapy for their indolent lymphoma than were the non-transplanted pts (p=0.005). For all 118 pts, the 2 and 5-year overall survival (OS) were 68% (95%CI: 59–76%) and 49% (95%CI: 37–59%). The 2-year OS for the non-SCT and any-SCT pts were 53% (95%CI: 39–68%) and 79% (95%CI: 69–89%). In non-SCT pts, those who were not exposed to chemotherapy prior to HT (n=16) experienced a 2-year OS of 81% (95%CI: 52–94%). The 2-year OS was 83% (95%CI: 70–91%) in the auto-SCT group, and 65% (95%CI: 39–83%) in the allo-SCT group. For HT pts age ≤60 (n=61), the 2- and 5-year OS were: 67% (95%CI: 53–77%) and 51% (95%CI: 34–65%) respectively. For auto-SCT pts age ≤60 (n=24), the 2-yr OS was 74% (95%CI: 51–87%). For non-transplanted pts age ≤60 (n=19), 2-yr OS was: 59% (95%CI: 32–78%). Amongst the non-transplanted pts age ≤60, the 2-year OS of the 6 patients naïve to chemotherapy prior to transformation was superior to that of the 13 patients who were exposed to chemotherapy prior to transformation (100% vs 35%, p=0.03). Conclusion Compared with historical series, the natural history of HT appears more favorable in the rituximab era. Long-term survival is seen with a variety of treatment strategies. In this largest prospective cohort of pts with strictly defined HT, pts who received auto-SCT for HT experienced a 2-year OS of 83%. Selected younger pts who are not exposed to chemotherapy prior to HT experience a prolonged survival even without transplantation. Future studies should evaluate predictive factors to determine which pts may benefit from a conservative approach to treatment of HT. Moreover, our study serves as a benchmark for future trials of novel approaches for HT. Disclosures: Zelenetz: Roche/Genentech: Advisor Other.

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Diffuse large B-cell lymphoma in colon confounded by prior history of colorectal cancer: A case report and literature review

Oncology Letters ◽

10.3892/ol.2016.4078 ◽

2016 ◽

Vol 11 (2) ◽

pp. 1493-1495

Author(s):

YANLING REN ◽

ZHILU CHEN ◽

CHUANYONG SU ◽

HONGYAN TONG ◽

WENBIN QIAN

Keyword(s):

Colorectal Cancer ◽

Case Report ◽

Literature Review ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Prior History ◽

Large B Cell Lymphoma ◽

History Of ◽

Large B Cell

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Eligibility for Car-T Trials: An Analysis of Selection Criteria and Survival Outcomes in Chemorefractory DLBCL

Blood ◽

10.1182/blood-2018-99-119794 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2911-2911

Author(s):

Prathima Reddy ◽

Alexandra Sokolova ◽

Victor A. Chow ◽

Ryan C. Lynch ◽

Mazyar Shadman ◽

...

Keyword(s):

Research Funding ◽

Performance Status ◽

Puget Sound ◽

B Cell Lymphoma ◽

Rapid Progression ◽

Cell Transplant ◽

Eligibility Criteria ◽

Historical Cohort ◽

Car T ◽

History Of

Abstract Background: Chemorefractory diffuse large B-cell lymphoma (DLBCL) is associated with poor outcomes. Recent Car-T therapy trials, including Zuma-1 which led to the first FDA approval of Car-T for DLBCL (Neelapu NEJM), have shown sustained complete remission, disease control, and long-term survival in a proportion of patients. As with all trials, results must be interepreted in context of study definitions and eligibility parameters. While selection bias is often discussed, little published data regarding specific eligibility requirements on accrual of DLBCL trials exists. To better understand factors influencing Car-T trial eligibility in DLBCL, and context for observed survival rates in Car-T trials, we examined chemorefractory DLBCL patients seen from 2011-2015 at our center, applying key eligibility criteria from Zuma-1 and describing likely reasons for trial exclusion. Methods: Pts with DLBCL seen at our institution from 2011-2015, who had received at least 2 lines of therapy, were reviewed under IRB approval to determine chemorefractory status based on ZUma-1 definition, and potential eligibility for the Zuma-1 trial. Chemorefractory status per Zuma 1 was defined as stable disease (lasting 6 months or less) or progressive disease as best response to most recent chemotherapy, or disease progression within 12 months of autologous stem cell transplant. "Chemorefractory date" was identified by the chart reviewed, based on biopsy or imaging showing progression, and served as the reference date for reviewing potential Zuma-1 eligibility in detail. Specifically, clinical data (ECOG, labs, organ function) within 8 weeks of chemorefractory date was examined to estimate potential Zuma-1 eligibility. On occasion, more remote studies (e.g., an echocardiogram >8 weeks prior) were applied when data appeared relevant. Descriptive statistics and a Kaplan-Meier survival estimate were performed, with a comparison between those potentially Zuma-1 eligible and those not. No attempt was made to compare outcomes among pts receiving specific therapies for chemorefractory DLBCL. The specific eligibility factors examined were: histology (DLBCL, PMBCL and tFL); prior therapy including history of allogeneic SCT; CNS involvement, performance status (ECOG 01- vs 2 or higher), laboratory parameters, cardiac disease, infectious comorbidities; history of second malignancy other than nonmelanoma skin cancer/in situ cance or FL; need for urgent therapy due to tumor mass effect or rapid progression. Results: Of 404 in our DLBCL database from 2011-2015, 163 had received at least 2 therapies and were examined. 36 had inadequate follow up, leaving 127 for detailed analysis. Of these 127, 78 were determined chemorefractory as per Zuma-1. Of these 78 chemorefractory pts, median age was 63 (18-82), 17 had transformed lymphoma, 30 underwent transplant (20 auto, 2 allo, 8 auto-allo), 18 relapsed within 1 year of autologous transplant, and 30 had primary refractory disease. 43 patients (55%) were deemed ineligible for Zuma-1 by retrospective review, for reasons given in Table 1. Figure 1 shows survival. Among "eligible" pts vs not: Median OS was 15 vs 8 months (eligible vs not, p=.04). 1 yr OS was 56% vs 33%, and 2 yrs OS 40% vs 22%. Conclusion: When applied to a historical cohort, about half of chemorefractory DLBCL pts met eligibility criteria for Zuma-1. The survival of "eligible" patients appears significantly better than others. A need for acute therapy (for rapid progression), ECOG performance status 2 or greater, and non-FL transformation (Richter's/CLL history) were the most common reasons for exclusion. Since these three features may not impact safety of Car-T therapy, but are associated with agrgessive disease, broadening eligibility around these criteria could represent a step toward testing Car-T therapies among those with greatest unmet need. Disclosures Lynch: T.G. Therapeutics: Research Funding; Rhizen Pharmaceuticals S.A.: Research Funding; Incyte Corporation: Research Funding; Takeda Pharmaceuticals: Research Funding; Johnson Graffe Keay Moniz & Wick LLP: Consultancy. Shadman:TG Therapeutics: Research Funding; AstraZeneca: Consultancy; Genentech: Research Funding; Verastem: Consultancy; Mustang Biopharma: Research Funding; Celgene: Research Funding; Gilead Sciences: Research Funding; AbbVie: Consultancy; Qilu Puget Sound Biotherapeutics: Consultancy; Acerta Pharma: Research Funding; Pharmacyclics: Research Funding; Genentech: Consultancy; Beigene: Research Funding. Till:Mustang Bio: Patents & Royalties, Research Funding. Shustov:SPECTRUM PHARMACEUTICALS: Consultancy, Research Funding. Gopal:Janssen: Consultancy, Research Funding; Asana: Consultancy; Takeda: Research Funding; Merck: Research Funding; BMS: Research Funding; Spectrum: Research Funding; Teva: Research Funding; Pfizer: Research Funding; Seattle Genetics: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; Brim: Consultancy; Aptevo: Consultancy; Incyte: Consultancy. Smith:Pharmacyclics: Research Funding; Genentech: Research Funding; Acerta Pharma BV: Research Funding; Incyte Corporation: Research Funding; Merck Sharp and Dohme Corp.: Consultancy, Research Funding; Portola Pharmaceuticals: Research Funding; Seattle Genetics: Research Funding.

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Next-Generation Sequencing of DDX41 in Myeloid Neoplasms Leads to Increased Detection of Germline Alterations

Frontiers in Oncology ◽

10.3389/fonc.2020.582213 ◽

2021 ◽

Vol 10 ◽

Author(s):

Sarah A. Bannon ◽

Mark J. Routbort ◽

Guillermo Montalban-Bravo ◽

Rohtesh S. Mehta ◽

Fatima Zahra Jelloul ◽

...

Keyword(s):

Genetic Counseling ◽

Next Generation Sequencing ◽

Family Members ◽

Hematologic Malignancies ◽

Prior History ◽

Cell Transplant ◽

Next Generation ◽

Myeloid Neoplasms ◽

History Of ◽

Generation Sequencing

Previously considered rare, inherited hematologic malignancies are increasingly identified. Germline mutations in the RNA helicase DDX41 predispose to increased lifetime risks of myeloid neoplasms with disease often occurring later in life which presents challenges for germline recognition. To improve identification of germline DDX41, individuals presenting with ≥1 DDX41 alteration on an institutional MDS/AML next-generation sequencing based panel with at least one at >40% variant allele frequency were flagged for review and genetic counseling referral. Of 5,801 individuals, 90 (1.5%) had ≥1 DDX41 mutation(s) identified. Thirty-eight (42%) patients with a median age of 66 years were referred for genetic counseling; thirty-one were male (81.5%). Thirty-five (92%) referred patients elected to pursue germline evaluation and in 33/35 (94%) a germline DDX41 variant was confirmed. Twenty-two patients (66%) with germline variants reported antecedent cytopenias, seven (21%) had a prior history of malignancy, and twenty-seven (82%) reported a family history of cancer. Predictive genetic testing for healthy family members under consideration as stem cell transplant donors was successfully performed in 11 family members, taking an average of 15 days. Near-heterozygous DDX41 mutations identified on next-generation sequencing, particularly nonsense/frameshift variants or those at recurrent germline “hot spots” are highly suggestive of a germline mutation. Next-generation sequencing screening is a feasible tool to screen unselected myeloid neoplasms for germline DDX41 mutations, enabling timely and appropriate care.

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