20 results on '"Daniels, Shari"'
Search Results
2. Pembrolizumab plus vorinostat induces responses in patients with Hodgkin lymphoma refractory to prior PD-1 blockade
- Author
-
Mei, Matthew, Chen, Lu, Godfrey, James, Song, Joo, Egelston, Colt, Puverel, Sandrine, Budde, L. Elizabeth, Armenian, Saro, Nikolaenko, Liana, Nwangwu, Mary, Guo, Weihua, Gao, Lei, Lee, Peter, Chen, Robert, Daniels, Shari, Kennedy, Neena, Peters, Lacolle, Zain, Jasmine, Rosen, Steven, Forman, Stephen, Popplewell, Leslie, Kwak, Larry, and Herrera, Alex F.
- Published
- 2023
- Full Text
- View/download PDF
3. Botulnum toxin type A (BoNT/A), the mandibular neuromuscular envelope, and bite jumping appliances : skeletal effects
- Author
-
Daniels, Shari Jane, Hunt, N., and Salih, V.
- Abstract
Background: Bite jumping appliances (BJA) are a common treatment modality for Class II malocclusions and yet studies have shown that the results are limited to mostly dentoalveolar correction. A better understanding of the role the muscles of mastication play in the action of these appliances is warranted. Botulinum neurotoxin type A (BoNT/A) is a useful research tool to decrease muscle function without impeding blood supply or causing scarring. Objectives: BoNT/A was used in this study in combination with BJA to assess cephalometrically the effects that muscular stretch have on the skeletal outcomes of bite jumping therapy. Methods: One hundred and twenty-eight inbred, juvenile, male, Wistar Kyoto (WKY) rats were randomly assigned to either: one of six short-term groups, or one of ten long-term groups (n = 8 per group). The short-term groups consisted of C (control), S (saline injection), B (BoNT/A injection), M (BJA), MB (BoNT/A injections plus BJA), MS (saline injection plus BJA). The long-term groups consisted of CL (control), BL (BoNT/A injection), BLR (BoNT/A repeat injection), SL (saline injection), SLR (saline repeat injection), ML (BJA), MBL (BoNT/A plus BJA), MBLR (BoNT/A repeat injection plus BJA), MSL (saline injection plus BJA), and MSLR (saline repeat injection plus BJA). In the BoNT/A injection groups the temporalis and deep masseter muscles were injected bilaterally with Dysport®. Equivalent volumes of saline were used within the sham injection groups. In the repeat injection groups, the injections were repeated weekly for the duration of the study. Digital lateral and dorsoventral cephalometric radiographs were taken at baseline (T0 = 28 days old) and weekly thereafter for 3 weeks until T3 (49 days of age) at which time the short-term groups were culled and all appliances removed. Additional radiographs were taken in the long-term groups at T4 (56 days of age), T5 (70 days of age), T6 (98 days of age), and T7 (126 days of age). The cephalometric program Viewbox 3.1® was used to create cephalometric analyses and obtain linear and angular measurements. After an initial repeatability study the variables were restricted to those deemed more accurate. Multiple comparisons between and within groups were conducted using one-way ANOVA with post-hoc test Tamhane. Results: Importantly, the total mandibular length (Co↔Dg) and horizontal projection of the mandible were increased in the MBL and MBLR groups. The condyles also maintained a more anterior position in the MBL and MBLR groups. Conclusions: The length of the mandible was only slightly affected in the experimental groups. The mandibular condyle and glenoid fossa of the rat does possess some adaptive capacity to altered extrinsic forces.
- Published
- 2018
4. Teacher-Writer Perceptions on the Essence of Writing: Influences, Identity and Habits of Mind to Sustain a Writing Life
- Author
-
Daniels, Shari Lynn
- Abstract
This body of work contains three articles that support the need for K-12 teachers to write professionally and personally. The research sought to explore the questions of initial influences to write, essentials to sustain writing and the relationship of teacher-writer development to self authorship. Much of the previous literature produced by scholars, authors and teacher-writers focus on the benefits for students when teachers are confident as writers. Student motivation to write rests on the beliefs of the teacher who provides a model for writing as this shapes student beliefs about themselves as writers. However, there is little research that provides substantial reasons for teachers to write as a benefit for their own professional and personal lives. The following articles present research findings to fill this gap. While few teachers identify themselves as writers or feel confidence in writing themselves, there are teachers that do. These teachers write with their students, blog, and write as a daily practice for educational and personal purposes. Once awakened to the writing life, these teachers become advocates for other teachers to write as well; they promote best practices on social media, provide professional development, participate in writing conferences and write books to motivate teachers to write. When teachers write themselves, they discover a sense of agency in using writing as a tool for both professional and personal growth. Two of the articles for this dissertation are based on qualitative case studies that explored the perceptions of ten K-12 teachers who write. These participants provided supportive data through a series of three interviews, two face-to-face and one through writing. The first study sought to examine the initial influences of each teacher-writer to understand the necessary conditions for teachers to be influenced to write, whether in childhood or as an adult. The second study, more phenomenological in nature, explored the essence of what keeps teacher-writers writing, including habits of mind and tools to develop these habits. The third study, a literature review, compared the relationship of teachers' development as a writer to the phases of self authorship. Each study intertwines as they support one another and contribute to the overall finding that writing, for teachers, is a path to discovering a meaningful and purposeful life. Data analysis revealed that initial influences for teachers to write included positive feedback from teachers or family members, a love of reading, or the early need to express creativity or satisfy curiosity. Teacher-writers with strong writing identities as children or young students received positive feedback that enabled them to continue to grow as writers, while those who were more challenged with the mechanics of writing or had teachers who were product focused, had a lack of self-efficacy in writing. If a negative writing identity was developed early on, revisiting writing histories to reshape their beliefs transformed their identity. Once teachers take steps to develop a writing identity, sustaining their practice is necessary to their growth as writers. Findings also unveiled four main purposes that drive teacher-writers to sustain their writing practices: to discover meaning, connect with others and themselves, as a commitment to learning, and for emotional well-being. Essential habits of mind included living with a sense of awareness, overcoming perfection, development of habits and rituals and ample time for solitude. Participants all described the personal joy writing brought them through discovery writing, creative play in writing and for expression of thoughts and emotions. Through each purpose, writing was a path to being alive in the world and in maintaining an energy that brought fulfillment and personal growth. Literature review findings in the third study describe the relationships of self-authorship and teacher-writer development stories of well-known teacher-writers. These teacher-writers began at an absolute knowledge stage with a limited knowledge of writing until a triggering moment caused cognitive dissonance. These crossroads propelled teachers to write themselves. Through writing, teachers cultivated their internal voice and learned to trust this voice over external authority. In continued writing, confidence and self-efficacy grew not only in writing, but in other areas of their lives. Their writing voice became their internal voice which was previously veiled or suppressed due to social contexts and expectations. Multiple implications are suggested for the integration of writing in teacher education programs. Ongoing practices can be more likely in a university setting as opposed to shorter professional development sessions in K-12 settings. Possibilities include creating safe writing communities in literacy courses and providing authentic purposes for pre-service teachers to write. Advisers who meet with students can model and suggest journaling as a way to explore big questions and to nurture an awareness of their thoughts and the world around them. (Abstract shortened by ProQuest.). [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]
- Published
- 2018
5. Results from a phase I trial of pembrolizumab plus vorinostat in relapsed/refractory B-cell non-Hodgkin lymphoma
- Author
-
Godfrey, James, primary, Mei, Matthew, additional, Chen, Lu, additional, Song, Joo Y., additional, Bedell, Victoria, additional, Budde, Elizabeth, additional, Armenian, Saro, additional, Puverel, Sandrine, additional, Nikolaenko, Liana, additional, Chen, Robert, additional, Daniels, Shari, additional, Kennedy, Neena, additional, Peters, Lacolle, additional, Rosen, Steven T., additional, Forman, Stephen J., additional, Popplewell, Leslie L., additional, Kwak, Larry W., additional, and Herrera, Alex F., additional
- Published
- 2023
- Full Text
- View/download PDF
6. Polatuzumab Vedotin Combined with R-ICE (PolaR-ICE) As Second-Line Therapy in Relapsed/Refractory Diffuse Large B-Cell Lymphoma
- Author
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Herrera, Alex F., primary, Chen, Lu, additional, Crombie, Jennifer L., additional, Cohen, Jonathon B., additional, Advani, Ranjana H., additional, LaCasce, Ann S., additional, Popplewell, Leslie L., additional, Puverel, Sandrine, additional, Peters, Lacolle, additional, Daniels, Shari, additional, Godfrey, James, additional, Shouse, Geoffrey, additional, Mei, Matthew, additional, Kambhampati, Swetha, additional, Budde, L. Elizabeth, additional, Nikolaenko, Liana, additional, Rosen, Steven T., additional, Kwak, Larry W., additional, Forman, Stephen J, additional, and Matasar, Matthew J., additional
- Published
- 2022
- Full Text
- View/download PDF
7. Pandemic Survival Tools for Teachers: Reading, Writing and Poetry
- Author
-
Daniels, Shari, primary and Michaelis, Caitlin, additional
- Published
- 2022
- Full Text
- View/download PDF
8. Atezolizumab Combined with Immunogenic Salvage Chemoimmunotherapy (R-GemOx+Atezo) in Patients with Transformed Diffuse Large B-Cell Lymphoma
- Author
-
Herrera, Alex F., primary, Othman, Tamer, additional, Frankel, Paul, additional, Allen, Pamela, additional, Popplewell, Leslie L., additional, Shouse, Geoffrey, additional, Siddiqi, Tanya, additional, Danilov, Alexey V., additional, Ruel, Nora, additional, Daniels, Shari, additional, Peters, Lacolle, additional, Khoo, Stella, additional, Rosen, Steven T., additional, Sharon, Elad, additional, and Tuscano, Joseph M, additional
- Published
- 2021
- Full Text
- View/download PDF
9. Pembrolizumab Plus Vorinostat Induces Responses in Patients with Hodgkin Lymphoma Who Are Refractory to Prior PD-1 Blockade
- Author
-
Herrera, Alex F., primary, Chen, Lu, additional, Budde, L. Elizabeth, additional, Armenian, Saro, additional, Nikolaenko, Liana, additional, Chen, Robert, additional, Daniels, Shari, additional, Kennedy, Neena, additional, Peters, Lacolle, additional, Rosen, Steven T., additional, Forman, Stephen J, additional, Popplewell, Leslie L., additional, Kwak, Larry W., additional, and Mei, Matthew, additional
- Published
- 2021
- Full Text
- View/download PDF
10. The Combination of Nivolumab and CC-486 Is Active in Hodgkin Lymphoma Refractory to PD-1 Blockade
- Author
-
Mei, Matthew G., Chen, Lu, Puverel, Sandrine, Budde, L. Elizabeth, Kambhampati, Swetha, Daniels, Shari, Dunning, Bev, Banez, Melissa, Kwak, Larry W., and Herrera, Alex F.
- Published
- 2023
- Full Text
- View/download PDF
11. The Path to Self-Authorship: The Pre-Service Teacher-Writer.
- Author
-
Daniels, Shari L. and Beck, Pamela
- Subjects
HABIT ,TEACHER development ,BEGINNING teachers ,COLLEGE teachers ,MIDDLE school teachers ,SPECIAL education teachers ,TEACHERS - Abstract
The article presents the discussion on roles, expectations, and responsibilities of teachers. Topics include providing pre-service teachers with abilities to be adaptive experts making decisions based on varying contexts, choose practices aligning with the beliefs and core values; and promoting self-authorship in pre-service teachers in preparation for the demands of being a first year teacher.
- Published
- 2022
12. Dynamin Inhibition Blocks Botulinum Neurotoxin Type A Endocytosis in Neurons and Delays Botulism
- Author
-
Harper, Callista B., primary, Martin, Sally, additional, Nguyen, Tam H., additional, Daniels, Shari J., additional, Lavidis, Nickolas A., additional, Popoff, Michel R., additional, Hadzic, Gordana, additional, Mariana, Anna, additional, Chau, Ngoc, additional, McCluskey, Adam, additional, Robinson, Phillip J., additional, and Meunier, Frederic A., additional
- Published
- 2011
- Full Text
- View/download PDF
13. Pembrolizumab plus vorinostat is highly active in Hodgkin lymphoma, including cases refractory to prior PD-1 blockade
- Author
-
Mei, Matthew, Chen, Lu, Godfrey, James, Song, Joo, Egelston, Colt, Budde, L. Elizabeth, Armenian, Saro, Nikolaenko, Liana, Guo, Weihua, Nwangwu, Mary, Gao, Lei, Lee, Peter, Chen, Robert, Daniels, Shari, Kennedy, Neena, Peters, Lacolle, Zain, Jasmine, Rosen, Steven, Forman, Stephen, Popplewell, Leslie, Kwak, Larry, and Herrera, Alex F.
- Abstract
•Pembrolizumab and vorinostat is well tolerated with a high ORR in RR cHL, with toxicities consistent with the known safety profiles of the 2 agents.•Pembrolizumab and vorinostat is active in RR cHL that is refractory to PD-1 blockade with an ORR of 56% in this subset.
- Published
- 2023
- Full Text
- View/download PDF
14. Equitable multilingualism? The case of Stellenbosch University Writing Laboratory
- Author
-
Daniels, Sharifa and Richards, Rose
- Subjects
academic literacy ,multilingualism ,transformation ,writing centre paradox ,writing centres ,Philology. Linguistics ,P1-1091 ,African languages and literature ,PL8000-8844 - Abstract
This article reflects on Stellenbosch University Writing Lab’s pedagogical approach to multilingualism and inclusivity within the complex and political nature of multilingual language policies at a South African university. The Writing Lab has always been promoted as a facility for all students, not just those in need of ‘remedial’ support. This was a departure from earlier academic literacies models that tended to view students from nondominant language groups in terms of deficits. Academic literacies research has pointed to the shortcomings of these earlier approaches and to the value conflicts that arise from them. We, in contrast, argue that Carter’s (2009) writing centre paradox provides a dynamic rhetorical space in which to explore issues around South African multilingualism and inclusivity in higher education, and for this reason we do not wish to resolve the paradox. Instead, we use it to critically appraise our type of equitable multilingualism and maintain and honour multivocality. We also argue that South African writing centres enjoy a somewhat different trajectory from that of many other academic literacies spaces by virtue of the one-to-one pedagogy and mutualistic approach we follow at these writing centres. This has allowed us simultaneously more agency and less agency and we need to use this paradoxical position strategically in our institutions. Using the Writing Lab as a case study, we reflect on the ways in which the Writing Lab gives life to its ethos of being a multilingual and inclusive space for academic transformation within the institution’s language policy. To support our reflections, we draw on descriptions of the organisational structure of the Lab, feedback received from strategic role players and observations of interactions performed in the various Lab spaces. We also consider the Writing Lab in terms of South African writing centre scholarship to see how the Lab’s philosophy and ethos compare with the ideals.
- Published
- 2017
- Full Text
- View/download PDF
15. From autopsy to autonomy in writing centres: Postgraduate students' response to two forms of feedback in a health professions education module
- Author
-
Daniels, Sharifa and Richards, Rose
- Subjects
Writing centres ,writing consultations ,peer feedback ,postgraduate students ,medical education ,Language and Literature ,African languages and literature ,PL8000-8844 - Abstract
In post-apartheid South Africa, writing centres exist in almost every university to address the academic writing needs of students. At Stellenbosch University Writing Lab, writing consultants use collaborative learning and peer feedback in their work with writers in one-to-one consultations. As part of a larger research project about how students in a Health Professions Education Master’s degree responded to different types of feedback, our study focuses on whether the feedback received in a writing consultation compares to, or differs from, the feedback from the class group members. Our findings suggest that in general the students were open to interventions such as writing consultations. Furthermore, peer feedback from both a class group member as well as a writing consultant was experienced as useful. The study further shows that the consultants’ approach to giving feedback was in line with the pedagogy practised in writing centres. The article concludes with measures that were implemented to address uncertainties identified in the study. We recommend that the purpose of consultations be clarified to lecturers, that consultations be integrated in the writing process before the assignment is marked and, to minimise role confusion, that consultants describe to students the way consultations work at the beginning of the consultation.
- Published
- 2016
- Full Text
- View/download PDF
16. The relationship between identity, language and teaching and learning in Higher Education in South Africa
- Author
-
Leibowitz, Brenda, Adendorff, Hanelie, Daniels, Shariefa, Loots, Ansie, Nakasa, Sipho, Ngxabazi, Nosipiwo, Van der Merwe, Antoinette, and Van Deventer, Idilette
- Subjects
identity ,language ,teaching and learning ,higher education ,South Africa ,Language and Literature ,African languages and literature ,PL8000-8844 - Abstract
he study on the relationship of identity, language and teaching and learning was conducted by a team of eight members at a higher education institution in the Western Cape. The aims of the research were to investigate the relationship between language, identity and learning, to show how this investigation can benefit dialogue about transformation, and to facilitate the research development of the team. The research design made use of narrative and educational biography in semi-structured interviews with 64 staff members and 100 students. The study supports views of identity as constructed and non-unitary. It shows how language, both as proficiency in the dominant medium of communication and as discourse, is a key component of identity in a higher education institution. The interviews demonstrated how, according to lecturers and students, language and discourse function as primary influences on individuals’ acculturation and integration into the academic community. According to the interviewees, language as a marker of identity is interwoven with other aspects of identity. It is both a resource and a source of identification and affiliation. The research demonstrated that dialogue and self reflection can be facilitated via research into identity, teaching and learning, and that this can be beneficial for both the interviewees and the research team.
- Published
- 2005
- Full Text
- View/download PDF
17. Teacher-Writer Perceptions On The Essence Of Writing: Influences, Identity And Habits Of Mind To Sustain A Writing Life
- Author
-
Daniels, Shari L
- Subjects
- essence of writing, teacher writer, writing, writing habits of mind, writing practices, writing purpose
- Abstract
This body of work contains three articles that support the need for K-12 teachers to write professionally and personally. The research sought to explore the questions of initial influences to write, essentials to sustain writing and the relationship of teacher-writer development to self authorship. Much of the previous literature produced by scholars, authors and teacher-writers focus on the benefits for students when teachers are confident as writers. Student motivation to write rests on the beliefs of the teacher who provides a model for writing as this shapes student beliefs about themselves as writers. However, there is little research that provides substantial reasons for teachers to write as a benefit for their own professional and personal lives. The following articles present research findings to fill this gap. While few teachers identify themselves as writers or feel confidence in writing themselves, there are teachers that do. These teachers write with their students, blog, and write as a daily practice for educational and personal purposes. Once awakened to the writing life, these teachers become advocates for other teachers to write as well; they promote best practices on social media, provide professional development, participate in writing conferences and write books to motivate teachers to write. When teachers write themselves, they discover a sense of agency in using writing as a tool for both professional and personal growth. Two of the articles for this dissertation are based on qualitative case studies that explored the perceptions of ten K-12 teachers who write. These participants provided supportive data through a series of three interviews, two face-to-face and one through writing. The first study sought to examine the initial influences of each teacher-writer to understand the necessary conditions for teachers to be influenced to write, whether in childhood or as an adult. The second study, more phenomenological in nature, explored the essence of what keeps teacher-writers writing, including habits of mind and tools to develop these habits. The third study, a literature review, compared the relationship of teachersâ development as a writer to the phases of self authorship. Each study intertwines as they support one another and contribute to the overall finding that writing, for teachers, is a path to discovering a meaningful and purposeful life. Data analysis revealed that initial influences for teachers to write included positive feedback from teachers or family members, a love of reading, or the early need to express creativity or satisfy curiosity. Teacher-writers with strong writing identities as children or young students received positive feedback that enabled them to continue to grow as writers, while those who were more challenged with the mechanics of writing or had teachers who were product focused, had a lack of self-efficacy in writing. If a negative writing identity was developed early on, revisiting writing histories to reshape their beliefs transformed their identity. Once teachers take steps to develop a writing identity, sustaining their practice is necessary to their growth as writers. Findings also unveiled four main purposes that drive teacher-writers to sustain their writing practices: to discover meaning, connect with others and themselves, as a commitment to learning, and for emotional well-being. Essential habits of mind included living with a sense of awareness, overcoming perfection, development of habits and rituals and ample time for solitude. Participants all described the personal joy writing brought them through discovery writing, creative play in writing and for expression of thoughts and emotions. Through each purpose, writing was a path to being alive in the world and in maintaining an energy that brought fulfillment and personal growth. Literature review findings in the third study describe the relationships of self-authorship and teacher-writer development stories of well-known teacher-writers. These teacher-writers began at an absolute knowledge stage with a limited knowledge of writing until a triggering moment caused cognitive dissonance. These crossroads propelled teachers to write themselves. Through writing, teachers cultivated their internal voice and learned to trust this voice over external authority. In continued writing, confidence and self-efficacy grew not only in writing, but in other areas of their lives. Their writing voice became their internal voice which was previously veiled or suppressed due to social contexts and expectations. Multiple implications are suggested for the integration of writing in teacher education programs. Ongoing practices can be more likely in a university setting as opposed to shorter professional development sessions in K-12 settings. Possibilities include creating safe writing communities in literacy courses and providing authentic purposes for pre-service teachers to write. Advisers who meet with students can model and suggest journaling as a way to explore big questions and to nurture an awareness of their thoughts and the world around them. Writing groups can be established to offer community and connections for pre-service teachers to write alongside of others. Faculty can teach the writing habits of mind to encourage a writing practice for pre-service teachers. Finally, teacher education faculty can develop curriculum that includes tools writers use to nurture the habits of mind that writers find are necessary to achieve their purpose. More research needs to be conducted in the area of purpose for teachers to write. This will continue to build supportive data to influence curriculum designers and faculty to place an emphasis on writing in their teacher education programs. Keywords: teacher as writer, writing habits of mind, writing attitudes, solitude, awareness, overcoming perfection, well-being, committed to learning, connection, discover meaning, essence of writing, joy, fulfillment, reading-writing connection, writing influences, sustaining writing practices, energy, aliveness
- Published
- 2018
18. Dynamin Inhibition Blocks Botulinum Neurotoxin Type A Endocytosis in Neurons and Delays Botulism.
- Author
-
Harpert, Callista B., Martin, Sally, Nguyent, Tam H., Daniels, Shari J., Lavidis, Nickolas A., Popoff, Michel R., Hadzic, Gordana, Mariana, Anna, Ngoc Chau, McCluskey, Adam, Robinson, Phillip J., and Meunier, Frederic A.
- Subjects
- *
BOTULINUM toxin , *BOTULISM , *ENDOCYTOSIS , *CELL physiology , *NEURONS , *AUTORECEPTORS , *ELECTRON microscopy - Abstract
The botulinum neurotoxins (BoNTs) are di-chain bacterial proteins responsible for the paralytic disease botulism. Following binding to the plasma membrane of cholinergic motor nerve terminals, BoNTs are internalized into an endocytic compartment. Although several endocytic pathways have been characterized in neurons, the molecular mechanism underpinning the uptake of BoNTs at the presynaptic nerve terminal is still unclear. Here, a recombinant BoNT/A heavy chain binding domain (Hc) was used to unravel the internalization pathway by fluorescence and electron microscopy. BoNT/A-Hc initially enters cultured hippocampal neurons in an activity-dependent manner into synaptic vesicles and clathrin-coated vesicles before also entering endosomal structures and multivesicular bodies. We found that inhibiting dynamin with the novel potent Dynasore analog, Dyngo-4a™, was sufficient to abolish BoNT/A-Hc internalization and BoNT/A-induced SNAP25 cleavage in hippocampal neurons. Dyngo-4a also interfered with BoNT/A-Hc internalization into motor nerve terminals. Furthermore, Dyngo-4a afforded protection against BoNT/A-induced paralysis at the rat hemidiaphragm. A significant delay of >30% in the onset of botulism was observed in mice injected with Dyngo-4a. Dynamin inhibition therefore provides a therapeutic avenue for the treatment of botulism and other diseases caused by pathogens sharing dynamin-dependent uptake mechanisms. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
19. Atezolizumab combined with immunogenic salvage chemoimmunotherapy in patients with transformed diffuse large B-cell lymphoma.
- Author
-
Othman T, Frankel P, Allen P, Popplewell LL, Shouse G, Siddiqi T, Danilov AV, Ruel N, Daniels S, Peters L, Khoo S, Rosen ST, Sharon E, Villalona-Calero M, Ruel C, Tuscano J, and Herrera AF
- Abstract
Patients with relapsed/refractory (R/R) transformed diffuse large B-cell lymphoma (DLBCL) from indolent B-cell lymphomas, including Richter transformation (RT), have a poor prognosis. PD-1/PD-L1 antibodies produce modest objective and complete response rates (ORR and CRR) in B-NHL as monotherapy but may synergize with immunogenic chemotherapies like gemcitabine and oxaliplatin (GemOx). Thus, we evaluated the safety and efficacy of atezolizumab plus rituximab and GemOx (R-GemOx+Atezo) in R/R transformed DLBCL, including RT. We conducted a phase I trial including patients with transformed DLBCL after ≥1 prior therapy. Patients received up to 4 cycles of R-GemOx-+Atezo. Patients in CR could then proceed to Ratezo maintenance until progression. A safety lead-in with dose-limiting toxicity (DLT) evaluation was enrolled to confirm the recommended phase 2 dose (RP2D), followed by 2 expansion cohorts: one for transformed follicular lymphoma (FL) and another for non-FL transformed DLBCL, including RT. Twenty-seven patients were enrolled. One of the 6 safety lead-in patients had a DLT attributed to atezolizumab, a grade 4 Stevens-Johnson syndrome (SJS). The most common grade ≥3 events were neutropenia (18.5%), lymphopenia (18.5%), and thrombocytopenia (14.8%). The overall and complete response rates (ORR and CRR) were 59% and 33%, respectively. The ORR and CRR in transformed FL were 79% and 43%, and 38% and 23% in transformed non-FL, respectively. The median PFS and OS of the total population were 4.2 and 7.7 months, respectively. R-GemOx+Atezo was well tolerated and demonstrated promising preliminary efficacy in patients with R/R transformed DLBCL.
- Published
- 2024
- Full Text
- View/download PDF
20. Results from a phase I trial of pembrolizumab plus vorinostat in relapsed/refractory B-cell non-Hodgkin lymphoma.
- Author
-
Godfrey J, Mei M, Chen L, Song JY, Bedell V, Budde E, Armenian S, Puverel S, Nikolaenko L, Chen R, Daniels S, Kennedy N, Peters L, Rosen ST, Forman SJ, Popplewell LL, Kwak LW, and Herrera AF
- Subjects
- Humans, Vorinostat, Neoplasm Recurrence, Local pathology, Lymphoma, Non-Hodgkin drug therapy, Lymphoma, Large B-Cell, Diffuse drug therapy, Lymphoma, Large B-Cell, Diffuse pathology, Lymphoma, Follicular, Antibodies, Monoclonal, Humanized
- Abstract
Outcomes after programmed death-1 (PD-1) blockade in B-cell lymphomas are disappointing with few durable responses. Histone deacetylase inhibitors exhibit favorable immunomodulatory effects and demonstrate synergistic anti-tumor immune responses with anti-PD-1 therapy in preclinical models. We, therefore, developed a phase I study to evaluate the safety and preliminary efficacy of pembrolizumab with vorinostat in relapsed/refractory B-cell lymphomas. Patients were treated in a dose-escalation cohort using a Rolling 6 design followed by an expansion cohort at the recommended phase II dose (R2PD). Fifty-two patients were enrolled (32 Hodgkin and 20 non-Hodgkin lymphoma [NHL]). Here, we report safety data from the dose escalation cohort, and the toxicity and efficacy within NHL patients. Vorinostat was administered twice daily on days 1-5 and 8-12 (dose-level [DL]1: 100 mg; DL2: 200 mg) and pembrolizumab (200 mg) was administered on day 1 of each 3-week cycle. Of six patients treated at DL1, one had a dose-limiting toxicity (DLT) (Stevens-Johnson syndrome [SJS]), and one of six had a DLT at DL2 (thromboembolism); therefore, DL2 was the RP2D. The patient developing SJS was treated with corticosteroids, infliximab, and cyclosporine but ultimately died of invasive fungal infection from the extensive immunosuppression used to treat the SJS. The most common adverse events were hypertension, diarrhea, and cytopenias. Of 20 NHL patients, nine had follicular lymphoma (FL) and 11 had diffuse large B-cell lymphoma (DLBCL). Five DLBCL patients had primary mediastinal B-cell lymphoma (PMBL). The complete and overall response rates (CR and ORR) were 11% and 22% for FL and 45% and 55% for all DLBCL. Amongst DLBCL, the CR and ORR was 80% and 80% for PMBL and 17% and 33% for non-PMBL. In conclusion, pembrolizumab with vorinostat was tolerable and produced responses in relapsed/refractory B-cell NHL, with particularly notable efficacy in PMBL (clinicaltrials gov. Identifier: NCT03150329).
- Published
- 2024
- Full Text
- View/download PDF
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