Geoffrey Shouse's research while affiliated with City of Hope National Medical Center and other places

Publications (37)

Article
Full-text available
Ibrutinib is effective in the treatment of relapsed/refractory (R/R) marginal zone lymphoma (MZL) with an overall response rate (ORR) of 48%. However, factors associated with response (or lack thereof) to ibrutinib in R/R MZL in clinical practice are largely unknown. To answer this question, we performed a multicenter (25 US centers) cohort study a...
Article
Most patients receiving CAR T-cell therapy (CAR-T) for aggressive B-cell lymphoma (B-NHL) will not experience a durable remission. There are several novel agents approved for the treatment relapsed, refractory aggressive B-NHL; however, it remains unclear how to sequence these therapies pre- and post-CAR-T (peri-CAR-T). We conducted a multicenter r...
Article
Introduction: CAR T-cell therapy (CART) has dramatically improved outcomes for patients (pts) with relapsed/refractory (r/r) DLBCL, but the majority of pts still have poor outcomes due to progressive disease and toxicities. Here we used a machine learning algorithm to rank the prognostic impact of specific comorbidities measured by the Cumulative I...
Article
Purpose of review: Treatment of non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) underwent paradigm shifts, with targeted agents rapidly displacing chemotherapy. Phosphoinotiside-3 kinase (PI3K) is essential for survival and proliferation of neoplastic B cells and has proven a tractable target in NHL, with four agents receiving FD...
Article
Background : Data for outcomes after autologous hematopoietic cell transplant (auto-HCT) in DLBCL patients ≥70 years are limited Objectives : Auto-HCT is feasible on older DLBCL patients Study Design : Using the CIBMTR database, we compared outcomes of auto-HCT in DLBCL patients aged 60-69 years (n=363) versus ≥70 years (n=103) between 2008 and 2...
Article
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Purpose of Review Validated metrics to optimize older adult patient selection for Chimeric Antigen Receptor T-cell therapy (CART) are lacking; however, some preliminary data suggests that geriatric assessments and cumulative illness rating score may be useful tools. In addition, interventions capable of enhancing outcomes in older adults receiving...
Article
Full-text available
Aberrant B-cell receptor (BCR) signaling is a key driver in lymphoid malignancies. Bruton tyrosine kinase (BTK) inhibitors that disrupt BCR signaling have received regulatory approvals in therapy of mantle cell lymphoma (MCL). However, responses are incomplete and patients who experience BTK inhibitor therapy failure have dire outcomes. CG-806 (lux...
Article
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Extranodal marginal zone lymphoma (EMZL) is a heterogeneous non-Hodgkin lymphoma. No consensus exists regarding the standard-of-care in patients with advanced-stage disease. Current recommendations are largely adapted from follicular lymphoma for which bendamustine with rituximab (BR) is an established approach. We analyzed the safety and efficacy...
Article
Background: Anti-CD19 chimeric antigen receptor T-cell therapy (CART) is a highly active therapy for relapsed/refractory (R/R) aggressive B-cell lymphoma. Nonetheless, most patients (pts) ultimately develop progressive disease (PD). There is little guidance on the optimal treatment approach(es) for these pts. We performed a multicenter retrospectiv...
Article
Introduction: CAR T-cell therapy has revolutionized the treatment of relapsed/refractory B cell lymphomas, providing hope to patients who previously faced dismal outcomes. Despite unprecedented efficacy including high response rates and a significant proportion of durable responses, significant toxicities are still prevalent. Toxicities related to...
Article
Introduction: CAR T-cell therapy (CART) has revolutionized the treatment landscape of aggressive B cell lymphoma (aBCL) in the relapsed/refractory (r/r) setting, including high-risk groups such as high grade B cell lymphoma (HGBCL), primary refractory disease, and chemo-resistant relapses. To date, however, there has been no data reported, on the o...
Article
Introduction: Comorbidities are common in CLL and associated with shorter overall survival (OS) and disease specific survival (Rotbain, Leukemia, 2021). Using an ensemble machine learning approach, we identified the comorbidities most strongly associated with event free survival (EFS) in CLL in order to construct the CLL-CI (Gordon et al, 2021). Ou...
Article
Introduction The treatment of aggressive B-cell NHL has evolved rapidly over the last 5 years, owing to the FDA approval of 3 CD19 CAR T-cell constructs (CARTs) along with other novel targeted therapies. Real world practice data suggest that CARTs have been successfully administered in populations typically excluded from clinical trials. However, d...
Article
Introduction: CAR T-cell therapy has dramatically improved outcomes for patients (pts) with relapsed/refractory (r/r) DLBCL, with some achieving durable response. Still, the majority of pts have poor outcomes with CAR-T due to progressive disease, while inherent characteristics may predispose pts to CAR-T toxicities. Tools quantifying frailty and c...
Article
Introduction: Chimeric antigen receptor T cell (CAR-T) therapy is an effective treatment for patients with relapsed/refractory diffuse large B cell lymphoma (DLBCL) or other B-cell lymphomas. However, the potent anti-lymphoma effect of CAR-T is balanced by the risk of acute toxicities, namely cytokine release syndrome (CRS) and Immune effector cell...
Article
Introduction: High-dose chemotherapy and autologous hematopoietic cell transplant (HDT-AHCT) is considered a standard-of-care (SOC) consolidation therapy for patients with aggressive systemic non-Hodgkin (NHL) and Hodgkin lymphomas (HL). This therapy is associated with improved survival in relapsed/refractory NHL and HL as well as in first complete...
Article
Background. Despite advances in targeted and cellular therapy, outcomes among patients with RT and tNHL remain dismal. Copanlisib (COPA) is a selective, small molecule, PI3K inhibitor which preferentially targets the p110αδ isoforms . COPA has shown clinical efficacy in NHL and is an approved therapy for follicular lymphoma (FL). Nivolumab is a PD-...
Article
Introduction: Diffuse large B-cell lymphomas (DLBCL) transformed from indolent B-cell non-Hodgkin lymphomas (B-NHL) or Richter transformation (RT) from chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) are associated with a poor prognosis, particularly in patients (pts) with relapsed/refractory (RR) disease. PD-1/PD-L1 blockade has prod...
Article
Introduction: Although anti-CD19 autologous chimeric antigen receptor (CAR) T-cell therapy has transformed the management of relapsed/refractory non-Hodgkin lymphoma (NHL), the majority of patients will ultimately relapse. The prognostic implications of early (1-month) metabolic response on ultimate outcome are still poorly defined, yet would have...
Article
Background: In November 2020, the U.S. Food and Drug Administration (FDA) issued emergency use authorization (EUA) for monoclonal antibody (mAb) therapy in patients with mild to moderate COVID-19 who are at high risk for disease progression. These mAbs reduce the risk of hospitalization in the general population. However, its efficacy and safety in...
Chapter
With the exploitation of adoptive immunotherapies, the outcomes of patients with relapsed and refractory B cell hematologic malignancies have seen drastic improvements. To this end, a paradigm shift away from toxic and ineffective chemotherapies has been visible with the FDA approval of genetically modified autologous T cell products designed to ex...
Article
Full-text available
Anti-PD-1 monoclonal antibodies yield high response rates in patients with relapsed/refractory classic Hodgkin lymphoma (cHL), but most patients will eventually progress. Allogeneic hematopoietic cell transplantation (alloHCT) after PD-1 blockade may be associated with increased toxicity, raising challenging questions about the role, timing, and op...
Article
Diffuse large B cell lymphoma (DLBCL) is a heterogeneous disease that is normally treated with combination chemotherapy combined with the anti-CD20 monoclonal antibody rituximab. Although about two-thirds of patients are cured with initial chemo-immunotherapy, a sizable minority of patients will have relapsed or refractory (r/r) DLBCL. Standard the...
Article
Purpose: Comorbid medical conditions define a subset of patients with chronic lymphocytic leukemia (CLL) with poor outcomes. However, which comorbidities are most predictive remains understudied. Experimental design: We conducted a retrospective analysis from 10 academic centers to ascertain the relative importance of comorbidities assessed by t...
Article
What is known and objective Treatment for diffuse large B-cell lymphoma (DLBCL) in persons with AIDS consists of chemotherapy alongside antiretroviral therapy (ART). To determine optimal HIV treatment, drug-drug interactions, toxic effects and ART resistance must be considered. Case description A 40-year-old man with drug-resistant HIV and DLBCL i...
Article
Introduction City of Hope (COH) was one of the first institutions to be granted Immune Effector Cell (IEC) Therapy accreditation by the Foundation for the Accreditation of Cellular Therapy, which supports our mission to provide safe, high quality patient care through expanded standardization. As part of the accreditation requirements, COH expanded...
Article
Introduction Ibrutinib was FDA approved for relapsed or refractory (R/R) marginal zone lymphoma (MZL) based on a phase II clinical trial that showed an overall response rate of 48% (Noy et al, Blood 2017). However, factors associated with response to ibrutinib in R/R MZL and outcomes of patients after progression on ibrutinib are unknown. Given the...
Conference Paper
Introduction: There is no standard induction therapy in extranodal marginal zone lymphoma (EMZL); current guidelines borrow from follicular lymphoma, where bendamustine and rituximab (BR) is an accepted standard. The data on BR in EMZL is limited (Rummel MJ et al. Lancet 2013 & Salar A et al. Blood 2017), so we explored BR activity as part of an in...
Article
Introduction The most common toxicities after chimeric antigen receptor (CAR) T cell therapy include cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS) and hematologic toxicity. The reported grade 3 and higher neutropenia, anemia and thrombocytopenia lasting longer than 30 days occurred in 15%, 3% and 18...
Article
Introduction Chimeric Antigen Receptor (CAR) T cell therapy has improved outcomes for relapsed and/or refractory (r/r) B cell lymphomas. Bridging therapy might be needed in some patients for disease control while CAR T product is being produced. Radiation therapy is known to control the growth of lymphoma and modulate tumor microenvironment, howeve...
Article
Full-text available
Background Data on patients with COVID-19 who have cancer are lacking. Here we characterise the outcomes of a cohort of patients with cancer and COVID-19 and identify potential prognostic factors for mortality and severe illness. Methods In this cohort study, we collected de-identified data on patients with active or previous malignancy, aged 18 y...
Article
Full-text available
Purpose of Review T cell lymphoproliferative disorders represent a diverse group of hematologic malignancies with poor prognosis underscoring the need for novel therapeutic approaches. Disruption of the JAK/STAT signaling pathway has been described in this group of blood cancers and may represent an approach for targeted therapy. Here, we summarize...
Article
Introduction: Anti-PD-1 monoclonal antibodies (mAbs) are highly active in relapsed/refractory classical Hodgkin lymphoma (cHL), but most patients (pts) will still relapse. Given this, allogeneic stem cell transplantation (alloHSCT) remains an important option for pts after PD-1 blockade, as it offers the possibility of cure. Prior reports have sugg...

Citations

... Another recently developed tool, MAGeCK-Flute, integrates MAGeCK and MAGeCK-VISPR providing new quality control and downstream analysis functions [117]. [39,52,53,65,67,76,90,97,122], HL [51], CLL [79], MM [91,123], ALL [27,[41][42][43]124], MDS [55] STARS [28] A method based on a gene-ranking system that calculates gene scores using a binomial model. ...
... Although predictive value of PET/CT to detect higher grade transformation in MZL is presently unknown, we suggest obtaining a tissue biopsy from highest SUV areas; especially, when significant discrepancies are observed between lesions. 37 We also suggest that all the patients will have multiparameter 4. SMZL that do not meet radiographically measurable disease criteria described herein are eligible for participation if lymphoma bone marrow infiltration is histologically confirmed and leads to clinically significant cytopenias (hemoglobin <10 g/dl, platelets <100 000/mm 3 , and/or neutrophils <1500/mm 3 ). Splenomegaly >13 cm should be considered measurable disease. ...
... The clinical heterogeneity of CLL is due to both disease biology and patient factors. [1][2][3][4][5] The typical clinical presentation of CLL involves leukemic involvement of bone marrow, peripheral blood and lymphoid organs which, as the disease progresses, causes systemic symptoms such as fevers, night sweats, fatigue and weight loss. Progressive infiltration of bone marrow and splenomegaly lead to cytopenias and enlarged lymph nodes may become symptomatic or impair adjacent organ function. ...
... The use of bispecific antibodies seems promising for R/R aggressive BCL patients, even after CAR T-cells failure 32 . Similar results have been reported in a US series, 26 suggesting that bispecific antibodies are a valid option. In our study, only a small sample of the censored patients (11patients) received this therapeutic strategy, and longer follow-up is needed for these patients, limiting any conclusions that can be drawn. ...
... Additionally, we were unable to determine the relationships between physical dysfunction, NMR measures, and supplement use or comorbidities. Given both supplement use and comorbidities are high in people with CLL, especially for those undergoing treatment, there is the possibility that these factors will influence our observations (53,54). Finally, we did not determine associations between outcomes and treatment factors, including the type of treatment (e.g., BTKi versus BCL2i) or the time on treatment dynamics. ...
... Treatment choices for R/R cHL patients who have failed brentuximab vedotin and PD-1 inhibitors are limited [15]. Allogeneic HSCT has significant toxicity, and patients with cHL who relapse or progress during treatment with brentuximab vedotin and PD-1 blockade still have a large unmet need for treatment [15][16][17]. ...
... There is recent evidence to suggest that radiation can induce changes in the immune system and can stimulate a significant immune response for a better therapeutic efficacy [21][22][23]. Radiation therapy can act as a bridging therapy for immunotherapies yielding better therapeutic efficacies with immunotherapy [24][25][26]. With a better understanding of the mechanistic basis and supporting experimental data, the interactions between radiation and immunotherapy can be better modeled and additional interaction terms can be introduced in the mathematical formulation to account for toxicity. ...
... Исходные характеристики этих пациентов имели благоприятный профиль: нормальный уровень лактатдегидрогеназы -ЛДГ (89%), низкий и средний риск по FLIPI (48 и 35%), отсутствие B-симптомов (97%) и низкую опухолевую нагрузку (72%). При медиане наблюдения 8 (5,(9)(10)(11)(12) лет только 64% этих пациентов в итоге начали противоопухолевую терапию (рис. 2) [2]. ...
... A recent study by Lee et al. [40] found that the susceptibility to SARS-CoV-2 infection is different among patients with different types of tumors. The UK coronavirus monitoring project (UKCCMP) and other researchers found that the patients with hematological cancers like leukemia, lymphoma, or myeloma were more vulnerable to SARS-CoV-2 than other forms of cancers [41][42][43]. ...
... There is always a concern among clinicians regarding immune related toxicities post alloHCT in patients with prior immunotherapies, plausibly because of immune alteration triggered by the treatment [18]. Blinatumomab is a bispecific T-cell engager that engages endogenous cytotoxic T-cells to kill CD19 expressing ALL blasts. ...