243 results on '"Matthew J. Matasar"'
Search Results
2. Polatuzumab vedotin plus bendamustine and rituximab or obinutuzumab in relapsed/refractory follicular lymphoma: a phase Ib/II study
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Christopher R. Flowers, Matthew J. Matasar, Alex F. Herrera, Mark Hertzberg, Sarit Assouline, Judit Demeter, Andrew McMillan, Amitkumar Mehta, Stephen Opat, Marek Trnňný, Lisa Musick, Jamie Hirata, Annie Yang, and Laurie H. Sehn
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Follicular lymphoma (FL) is the most common type of indolent non-Hodgkin lymphoma. Despite treatment advances that have improved outcomes for patients with relapsed or refractory (R/R) FL, many patients still die from progressive disease or treatment-related toxicities. In the phase Ib/II GO29365 study (clinicaltrials.gov 02257567), the safety and efficacy of polatuzumab vedotin plus bendamustine and rituximab (Pola-BR) versus bendamustine and rituximab (BR) alone, and polatuzumab vedotin plus bendamustine and obinutuzumab (Pola-BG) as a single-arm cohort were evaluated in patients with R/R FL. Following the phase Ib safety run-in, patients were randomized 1:1 to receive Pola-BR or BR alone in the phase II stage; a separate non-randomized Pola-BG cohort was examined in the phase Ib/II expansion stage. Primary endpoints included safety and tolerability (phase Ib) and positron emission tomography complete response (PET-CR) rate by independent review committee (phase II). Overall, 112 patients were enrolled (phase Ib safety run-in: Pola-BR, N=6; phase II randomized cohort: Pola-BR, N=39; BR, N=41; phase Ib/II expansion cohort: Pola-BG, N=26). PET-CR rates were 66.7% (phase Ib safety run-in, Pola-BR); 69.2% (phase II randomized, Pola-BR); 63.4% (phase II randomized, BR); and 65.4% (phase Ib/II expansion Pola-BG). There was a higher occurrence of cytopenias with Pola-BR and Pola-BG than with BR; serious adverse events were more frequent with Pola-BR (61.4%) and Pola-BG (46.2%) than with BR (29.3%). Overall, this analysis does not demonstrate a benefit of adding Pola to BR or BG regimens for patients with R/R FL.
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- 2023
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3. Immunochemotherapy plus lenalidomide for high-risk mantle cell lymphoma with measurable residual disease evaluation
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Zachary D. Epstein-Peterson, Esther Drill, Umut Aypar, Connie Lee Batlevi, Philip Caron, Ahmet Dogan, Pamela Drullinsky, John Gerecitano, Paul A. Hamlin, Caleb Ho, Allison Jacob, Ashlee Joseph, Leana Laraque, Matthew J. Matasar, Alison J. Moskowitz, Craig H. Moskowitz, Chelsea Mullins, Colette Owens, Gilles Salles, Heiko Schöder, David J. Straus, Anas Younes, Andrew D. Zelenetz, and Anita Kumar
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Chemoimmunotherapy followed by consolidative high-dose therapy with autologous stem cell rescue was a standard upfront treatment for fit patients with mantle cell lymphoma (MCL) in first remission; however, treatment paradigms are evolving in the era of novel therapies. Lenalidomide is an immunomodulatory agent with known efficacy in treating MCL. We conducted a single-center, investigator-initiated, phase II study of immunochemotherapy incorporating lenalidomide, without autologous stem cell transplant consolidation, enriching for patients with high-risk MCL (clinicaltrials gov. Identifier: NCT02633137). Patients received four cycles of lenalidomide-R-CHOP, two cycles of R-HiDAC, and six cycles of R-lenalidomide. The primary endpoint was rate of 3-year progression-free survival. We measured measurable residual disease (MRD) using a next-generation sequencing-based assay after each phase of treatment and at 6 months following end-oftreatment. We enrolled 49 patients of which 47 were response evaluable. By intent-to-treat, rates of overall and complete response were equivalent at 88% (43/49), one patient with stable disease, and two patients had disease progression during study; 3-year progression-free survival was 63% (primary endpoint not met) and differed by TP53 status (78% wild-type vs. 38% ALT; P=0.043). MRD status was prognostic and predicted long-term outcomes following R-HiDAC and at 6 months following end-of-treatment. In a high-dose therapy-sparing, intensive approach, we achieved favorable outcomes in TP53- wild-type MCL, including high-risk cases. We confirmed that sequential MRD assessment is a powerful prognostic tool in patients with MCL.
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- 2023
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4. Clinical outcomes with use of radiation therapy and risk of transformation in early-stage follicular lymphoma
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Fushen Sha, Michelle Okwali, Anna Alperovich, Philip C. Caron, Lorenzo Falchi, Audrey Hamilton, Paul A. Hamlin, Steven M. Horwitz, Erel Joffe, Niloufer Khan, Anita Kumar, Matthew J. Matasar, Alison J. Moskowitz, Ariela Noy, Colette Owens, Lia M. Palomba, Ildefonso Rodriguez-Rivera, David Straus, Gottfried von Keudell, Andrew D. Zelenetz, Joachim Yahalom, Ahmet Dogan, Heiko Schöder, Venkatraman E. Seshan, Gilles Salles, Anas Younes, and Connie L. Batlevi
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Between 1998 and 2009, a total of 295 patients (median age 58, 53% females) with newly diagnosed early-stage follicular lymphoma (FL) were managed at Memorial Sloan Kettering Cancer Center. Approximately half of patients (137, 46%) underwent initial observation and half (158, 54%) immediate treatment: radiation alone (n = 108), systemic treatment alone (n = 29), or combined modality treatment (n = 21). Median follow-up was 8.4 years (range 0.3–17.2), and 10-year overall survival (OS) was 87.2%. OS was similar between initially-observed and immediately-treated patients (hazard ratio [HR]: 1.25, 95% CI: 0.67–2.36, p = 0.49). For patients receiving radiation alone, 5-year OS was 98.0%. Patients selected for systemic therapy alone had high-risk baseline features and had shorter OS than patients treated with radiation alone (HR 3.38, 95% CI 1.29–8.86, p = 0.01). Combined modality treatment did not yield superior survival compared with radiation alone (P > 0.05) but was associated with better progression-free survival (HR 0.36, 95% CI 0.14–0.90, p = 0.03). The rate of transformation increased steadily over time and was 4.2% at 5 years and 10.8% at 10 years. This modern-era analysis rationalized the role of initial observation in patients with early-stage FL although patients receiving radiation therapy also demonstrate excellent outcome.
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- 2022
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5. Prophylaxis with intrathecal or high-dose methotrexate in diffuse large B-cell lymphoma and high risk of CNS relapse
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Sabela Bobillo, Erel Joffe, David Sermer, Patrizia Mondello, Paola Ghione, Philip C. Caron, Audrey Hamilton, Paul A. Hamlin, Steven M. Horwitz, Anita Kumar, Matthew J. Matasar, Connie L. Batlevi, Alison Moskowitz, Ariela Noy, Collette N. Owens, M. Lia Palomba, David Straus, Gottfried von Keudell, Ahmet Dogan, Andrew D. Zelenetz, Venkatraman E. Seshan, and Anas Younes
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Although methotrexate (MTX) is the most widely used therapy for central nervous system (CNS) prophylaxis in patients with diffuse large B-cell lymphoma (DLBCL), the optimal regimen remains unclear. We examined the efficacy of different prophylactic regimens in 585 patients with newly diagnosed DLBCL and high-risk for CNS relapse, treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or R-CHOP-like regimens from 2001 to 2017, of whom 295 (50%) received prophylaxis. Intrathecal (IT) MTX was given to 253 (86%) and high-dose MTX (HD-MTX) to 42 (14%). After a median follow-up of 6.8 years, 36 of 585 patients relapsed in the CNS, of whom 14 had received prophylaxis. The CNS relapse risk at 1 year was lower for patients who received prophylaxis than patients who did not: 2% vs. 7.1%. However, the difference became less significant over time (5-year risk 5.6% vs. 7.5%), indicating prophylaxis tended to delay CNS relapse rather than prevent it. Furthermore, the CNS relapse risk was similar in patients who received IT and HD-MTX (5-year risk 5.6% vs. 5.2%). Collectively, our data indicate the benefit of MTX for CNS prophylaxis is transient, highlighting the need for more effective prophylactic regimens. In addition, our results failed to demonstrate a clinical advantage for the HD-MTX regimen.
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- 2021
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6. Outcomes of Patients with Positive Interim Positron Emission Tomography (PET) Continuing ABVD in the Clinical Setting
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Serena Zheng, Kanika Gupta, Piyush Goyal, Reiko Nakajima, Laure Michaud, Connie Lee Batlevi, Paul A. Hamlin, Steven Horwitz, Anita Kumar, Matthew J. Matasar, Alison J. Moskowitz, Craig H. Moskowitz, Ariela Noy, M. Lia Palomba, David J. Straus, Gottfried Von Keudell, Lorenzo Falchi, Joachim Yahalom, Andrew D. Zelenetz, Anas Younes, Gilles Salles, Heiko Schöder, and Erel Joffe
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PET adapted therapy ,ABVD ,Hodgkin’s lymphoma ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Recent prospective clinical trial data suggest that patients with Hodgkin’s lymphoma who continue treatment with ABVD, despite failing to attain a complete metabolic response on interim PET (PET2+), may fare better than previously published. We describe the outcomes of PET2+ patients who continued ABVD and compare the performance of a quantitative measure based on the lesion-to-liver SUV ratio (LLS qPET2+) to that of the subjective Deauville criteria (dvPET2+). We analyzed all patients with newly diagnosed advanced-stage Hodgkin lymphoma treated with frontline ABVD at the Memorial Sloan Kettering Cancer Center between 2008 and 2017. Eligibility was set to correspond with the RATHL inclusion criteria. Images were reviewed by two nuclear medicine physicians and discordant cases were resolved with a third expert in consensus. qPET2+ was defined as LLS ≥ 1.3. We identified 227 patients of whom 25% (57) were qPET2+, but only 14% (31) were dvPET2+. Forty-eight patients (84%) continued ABVD with a 3-year PFS of 70% for qPET2+ and 64% for dvPET2+. In conclusion, interim PET interpretation in clinical practice may be associated with a higher rate of scans deemed positive. Irrespective of the criteria for PET2 positivity, a subset of patients may continue ABVD without a dismal outcome.
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- 2023
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7. Prephase rituximab/prednisone therapy and aging-related, proinflammatory cytokine milieu in older, vulnerable patients with newly diagnosed diffuse large B-cell lymphoma
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Richard J. Lin, Colette N. Owens, Esther Drill, Augustine Iannotta, Mayan Oliveros, Dylan L. Schick, Ariela Noy, John F. Gerecitano, Pamela R. Drullinsky, Philip C. Caron, Anita Kumar, Matthew J. Matasar, Craig Moskowitz, Beatriz Korc-Grodzicki, Andrew D. Zelenetz, Gilles A. Salles, and Paul A. Hamlin
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Diffuse large B-cell lymphoma (DLBCL) predominantly affects older adults with suboptimal therapeutic outcomes due to increased treatment-related mortality and toxicities in vulnerable patients, clinically defined by geriatric impairments such as functional limitation, multimorbidity, or cognitive deficits. In this prospective pilot study, we evaluated a rituximab/prednisone prephase treatment strategy in 33 older, vulnerable patients with newly diagnosed DLBCL, defined by either age ≥70 years or age 60-70 years with Karnofsky performance scale (KPS)
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- 2021
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8. Pilot trial of ibrutinib in patients with relapsed or refractory T-cell lymphoma
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Anita Kumar, Santosha Vardhana, Alison J. Moskowitz, Pierluigi Porcu, Ahmet Dogan, Jason A. Dubovsky, Matthew J. Matasar, Zhigang Zhang, Anas Younes, and Steven M. Horwitz
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Specialties of internal medicine ,RC581-951 - Abstract
Abstract: Ibrutinib has previously been shown to inhibit Bruton's tyrosine kinase (BTK) and interleukin-2–inducible T-cell kinase (ITK), which mediate B-cell and T-cell receptor signaling, respectively. BTK inhibition with ibrutinib has demonstrated impressive clinical responses in a variety of B-cell malignancies. Whether ibrutinib inhibition of ITK can lead to clinical response in T-cell malignancies is unknown. We hypothesized that ibrutinib-mediated ITK inhibition in T-cell lymphoma would result in decreased signaling through the T-cell receptor pathway and promote antitumor immune response by driving selective cytotoxic Th1 CD4 effector T-cell differentiation. This pilot clinical trial evaluated 2 dose levels of ibrutinib: 560 and 840 mg orally daily. Fourteen patients with relapsed, refractory peripheral T-cell lymphoma and cutaneous T-cell lymphoma were enrolled. Both dose levels were safe and well tolerated, and no dose-limiting toxicities were observed. One patient achieved a partial response (overall response rate, 8% [1/13]). ITK occupancy studies demonstrated a mean occupancy of 50% (range, 15%-80%). Higher ITK occupancy of more than 50% correlated with higher serum levels of tumor necrosis factor-α and interferon-γ and favored a Th1 phenotype. Our data suggest that ibrutinib inhibition of ITK has limited clinical activity in T-cell lymphoma. This study is registered at www.clinicaltrials.gov as #NCT02309580.
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- 2018
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9. Pattern and Prognostic Implications of Cardiac Metastases Among Patients With Advanced Systemic Cancer Assessed With Cardiac Magnetic Resonance Imaging
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Shawn C. Pun, Andrew Plodkowski, Matthew J. Matasar, Yulia Lakhman, Darragh F. Halpenny, Dipti Gupta, Chaya Moskowitz, Jiwon Kim, Richard Steingart, and Jonathan W. Weinsaft
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cardiac metastases ,cardiac tumor ,cardio‐oncology ,cardiovascular magnetic resonance ,oncology ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
BackgroundCardiac magnetic resonance (CMR) imaging is well validated for tissue characterization of cardiac masses but has not been applied to study pattern and prognostic implications of cardiac metastases (CMETs) among patients with systemic cancer. Methods and ResultsThe population consisted of 60 patients with stage IV cancer (32 patients with CMETs, 28 diagnosis‐matched controls) undergoing CMR. CMET was defined as a discrete mass with vascular tissue properties on delayed enhancement CMR. CMET‐positive patients and controls had similar clinical characteristics, cardiac geometry, and function (P=NS). Leading cancer types associated with CMET were sarcoma, melanoma, and gastrointestinal. Patients with CMETs had similar distribution of extracardiac metastatic disease compared with controls (organs involved: 3.4±2.0 versus 2.7±1.9, P=0.17). In 94% of patients with CMETs, there were metastases involving ≥1 extracardiac organ (66% lung involvement). CMET location varied (right ventricle 44%, right atrium 19%, left ventricle 28%, left atrium 9%, pericardial 25%); 22% of cases had multichamber involvement. Right‐sided chamber involvement was common in hematologic/lymphatic spread (67%); pericardial involvement was common with direct spread (64%). Regarding tissue properties on delayed enhancement CMR, CMETs commonly (59%) demonstrated heterogeneous enhancement (41% diffuse enhancement). Heterogeneous lesions were larger and had increased border irregularity (P
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- 2016
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10. Polatuzumab Vedotin Plus Bendamustine and Rituximab in Relapsed/Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL): Final Results of a Phase Ib/II Randomized Study and Single-Arm Extension (Ext) Study
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Laurie H. Sehn, Mark Hertzberg, Stephen Opat, Alex F. Herrera, Sarit Assouline, Christopher R. Flowers, Tae Min Kim, Andrew K. McMillan, Muhit Özcan, Violaine Safar, Gilles Salles, Jamie Hirata, Annie Yang, Lisa Musick, and Matthew J. Matasar
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
11. Risk Profiling of Patients with Previously Untreated Diffuse Large B-Cell Lymphoma (DLBCL) By Measuring Circulating Tumor DNA (ctDNA): Results from the POLARIX Study
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Alex F. Herrera, Ronald McCord, Patrick Kimes, Fabrice Jardin, Georg Lenz, Marek Trneny, Christopher R. Flowers, Laurie H. Sehn, Gilles Salles, Jeff P. Sharman, Hervé Tilly, Jonathan W. Friedberg, Charles Herbaux, Matthew J. Matasar, Corinne Haioun, Samuel Tracy, Jamie Hirata, Calvin Lee, Yanwen Jiang, and Franck Morschhauser
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
12. Mosunetuzumab Monotherapy Demonstrates Durable Efficacy with a Manageable Safety Profile in Patients with Relapsed/Refractory Follicular Lymphoma Who Received ≥2 Prior Therapies: Updated Results from a Pivotal Phase II Study
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Nancy L. Bartlett, Laurie H. Sehn, Matthew J. Matasar, Stephen J. Schuster, Sarit Assouline, Pratyush Giri, John Kuruvilla, Miguel Canales, Sascha Dietrich, Keith Fay, Matthew Ku, Loretta J. Nastoupil, Michael C. Wei, Shen Yin, Iris To, Huang Huang, Juliana Min, Elicia Penuel, and L. Elizabeth Budde
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
13. Pooled Safety Analysis from Phase I-III Studies for Patients with Hematological Malignancies Treated with the PI3K Inhibitor Copanlisib
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Pier Luigi Zinzani, Muhit Özcan, Marcelo Capra, Armando Santoro, Panayiotis Panayiotidis, Krimo Bouabdallah, Wojciech Jurczak, Charles Phelps, Florian JR Hiemeyer, Lidia Mongay Soler, Jose Garcia-Vargas, Barrett H. Childs, Georg Lenz, Matthew J. Matasar, and Martin Dreyling
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
14. Cardiovascular risk factors, radiation therapy, and myocardial infarction among lymphoma survivors
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Talya Salz, Emily C. Zabor, Peter De Nully Brown, Susanne Oksbjerg Dalton, Nirupa J. Raghunathan, Matthew J. Matasar, Richard Steingart, Henrik Hjalgrim, Lena Specht, Andrew J. Vickers, Kevin C. Oeffinger, and Christoffer Johansen
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Adult ,Lymphoma ,Lymphoma, Non-Hodgkin ,Myocardial Infarction ,Hematology ,General Medicine ,Middle Aged ,Oncology ,Cardiovascular Diseases ,Risk Factors ,Heart Disease Risk Factors ,Humans ,Radiology, Nuclear Medicine and imaging ,Survivors - Abstract
Mediastinal radiation is associated with increased risk of myocardial infarction (MI) among non-Hodgkin lymphoma (NHL) survivors.To evaluate how preexisting cardiovascular risk factors (CVRFs) modify the association of mediastinal radiation and MI among a national population of NHL survivors with a range of CVRFs.Using Danish registries, we identified adults diagnosed with lymphoma 2000-2010. We assessed MI from one year after diagnosis through 2016. We ascertained CVRFs (hypertension, dyslipidemia, and diabetes), vascular disease, and intrinsic heart disease prevalent at lymphoma diagnosis. We used multivariable Cox regression to test the interaction between preexisting CVRFs and receipt of mediastinal radiation on subsequent MI.Among 3151 NHL survivors (median age 63, median follow-up 6.5 years), 96 were diagnosed with MI. Before lymphoma, 32% of survivors had ≥1 CVRF. 8.5% of survivors received mediastinal radiation. In multivariable analysis, we found that mediastinal radiation (HR = 1.96; 95% CI = 1.09-3.52), and presence of ≥1 CVRF (HR = 2.71; 95% CI = 1.77-4.15) were associated with an increased risk of MI. Although there was no interaction on the relative scale (Patients with CVRFs have an importantly higher risk of subsequent MI if they have mediastinal radiation. Routine evaluation of CVRFs and optimal treatment of preexisting cardiovascular disease should continue after receiving cancer therapy. In patients with CVRFs, mediastinal radiation should only be given if oncologic benefit clearly outweighs cardiovascular harm.
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- 2022
15. TP53 mutations identify high-risk events for peripheral T-cell lymphoma treated with CHOP-based chemotherapy
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William T Johnson, Nivetha Ganesan, Zachary D Epstein-Peterson, Alison J. Moskowitz, Robert N Stuver, Catherine R Maccaro, Natasha Galasso, Tiffany Chang, Niloufer Khan, Umut Aypar, Natasha E Lewis, Andrew D Zelenetz, M. Lia Palomba, Matthew J Matasar, Ariela Noy, Audrey M Hamilton, Paul A. Hamlin, Philip C Caron, David J Straus, Andrew M Intlekofer, Connie Lee Batlevi, Anita Kumar, Colette N Owens, Craig S Sauter, Lorenzo Falchi, Jennifer K Lue, Santosha A Vardhana, Gilles A. Salles, Ahmet Dogan, Nikolaus D Schultz, Maria E Arcila, and Steven M Horwitz
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Hematology - Abstract
Nodal peripheral T-cell lymphomas (PTCL), the most common PTCLs, are generally treated with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)-based curative-intent chemotherapy. Recent molecular data have assisted in prognosticating these PTCLs, but most reports lack detailed baseline clinical characteristics and treatment courses. We retrospectively evaluated cases of PTCL treated with CHOP-based chemotherapy that had tumors sequenced by the Memorial Sloan Kettering Integrated Mutational Profiling of Actionable Cancer Targets (MSK-IMPACT) next-generation sequencing (NGS) panel to identify variables correlating with inferior survival. We identified 132 patients who met these criteria. Clinical factors correlating with increased risk of progression (by multivariate analysis) were advanced-stage disease (HR, 5.1; 95% CI, 1.1-22.5, P=.03) and bone marrow involvement (HR, 3.0; 95% CI, 1.1-8.4; P=.04). The only somatic genetic aberrancies correlating with inferior progression-free survival (PFS) were TP53 mutations (HR, 3.1; 95% CI, 1.4-6.8; P=.005) and TP53/17p deletions (HR, 4.1; 95% CI, 1.1-15.0, P=.03). PFS remained inferior when stratifying by TP53 mutation status, with a median PFS of 4.5 months (95% CI, 3.8-13.9) for PTCL with a TP53 mutation (n=21) vs 10.5 months (95% CI, 7.8-18.1; P
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- 2023
16. Mosunetuzumab monotherapy is active and tolerable in patients with relapsed/refractory diffuse large B-cell lymphoma
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Nancy L. Bartlett, Sarit Assouline, Pratyush Giri, Stephen J. Schuster, Chan Yoon Y Cheah, Matthew J Matasar, Gareth P. Gregory, Dok-Hyun Yoon, Mazyar Shadman, Keith Fay, Sung-Soo Yoon, Carlos Panizo, Ian W. Flinn, Anna Johnston, Francesc Bosch, Laurie H Sehn, Michael C. Wei, Shen Yin, Iris To, Chi-Chung Li, Huang Huang, Antonia Kwan, Elicia Penuel, and elizabeth Elizabeth budde
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Hematology - Abstract
As part of a phase 1/2 study, this single-arm expansion cohort established the efficacy and safety of mosunetuzumab monotherapy in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) (received >=2 prior lines of therapy). Intravenous mosunetuzumab was administered with cycle (C)1 step-up dosing for cytokine release syndrome (CRS) mitigation: C1 day (D) 1: 1 mg; C1D8 2 mg; C1D15 and C2D1: 60 mg; C3 + D1: 30 mg. Hospitalization was not mandatory. Patients with complete response (CR) completed treatment after C8; those with partial response or stable disease continued treatment for a total of 17 cycles. The primary endpoint was CR rate (best response) by Independent Review Facility, assessed against a historical control CR rate (20%). Eighty-eight patients (73.9% de-novo DLBCL; 26.1% transformed follicular lymphoma) were enrolled; all had received prior anthracycline and anti-CD20 therapy. Overall response and CR rates were 42.0% (95% confidence interval [CI], 31.6-53.1) and 23.9% (95% CI, 15.4-34.1, respectively; CR rate did not reach statistical significance versus the historical control [P = 0.36]). Median time to first response was 1.4 months. Median progression-free survival was 3.2 months (95% CI: 2.2, 5.3). The CR rate in 26 patients who received prior CAR-T therapy was 12%. CRS was one of the most common adverse events (26.1% of patients); predominantly grade 1 to 2 and primarily in C1. Four patients (4.5%) discontinued mosunetuzumab due to adverse events. Mosunetuzumab demonstrated notable efficacy and a manageable safety profile in patients with R/R DLBCL, including those previously treated with CAR-Ts.
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- 2023
17. Low incidence of cardiotoxicity in patients with <scp>non‐Hodgkin</scp> lymphoma receiving <scp>EPOCH</scp> after prior anthracycline exposure
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Michael J. Buege, Esther Drill, Steven M. Horwitz, Andréa LeVoir, Terry Pak, Tim J. Peterson, Phuong H. Dao, and Matthew J. Matasar
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Hematology ,General Medicine - Published
- 2023
18. Brentuximab Vedotin Combined with Chemotherapy in Newly Diagnosed, Early-Stage, Unfavorable-Risk Hodgkin Lymphoma: Extended Follow-up with Evaluation of Baseline Metabolic Tumor Volume and PET2
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Robert Stuver, Laure Michaud, Carla Casulo, Ranjana H. Advani, Elizabeth L. Budde, Paul M. Barr, Connie Lee Batlevi, Philip C Caron, Louis S. Constine, Savita Dandapani, Pamela Drullinsky, Jonathan W. Friedberg, Clare Grieve, Audrey Hamilton, Paul A. Hamlin, Richard Hoppe, Steven M. Horwitz, Niloufer Khan, Matthew J. Matasar, Ariela Noy, M.Lia Palomba, Heiko Schoder, David J. Straus, Shreya Vemuri, Joachim Yahalom, Joanna C. Yang, Anas Younes, Andrew D. Zelenetz, Craig H. Moskowitz, Anita Kumar, and Alison J. Moskowitz
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
19. Subcutaneous Mosunetuzumab Is Active with a Manageable Safety Profile in Patients (pts) with Relapsed/Refractory (R/R) B-Cell Non-Hodgkin Lymphomas (B-NHLs): Updated Results from a Phase I/II Study
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Elizabeth L. Budde, Nancy L. Bartlett, Pratyush Giri, Stephen J. Schuster, Sarit Assouline, Sung-Soo Yoon, Keith Fay, Matthew J. Matasar, Norma C. Gutierrez, Paula Marlton, Martin Dreyling, Dok Hyun Yoon, Georg Hess, John Radford, Volker Wiebking, Shen Yin, Eva Cybulski, David C. Turner, Huang Huang, Mingzhu Zhou, Elicia Penuel, Michael C. Wei, and Laurie H. Sehn
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
20. Pharmacodynamics and Biomarker Correlates of Imvotamab (IGM-2323), the First-in-Class CD20xCD3 Bispecific IgM Antibody with Dual Mechanisms of Action, in Patients with Advanced B Cell Malignancies
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Genevive H. Hernandez, John So, Kathryn A. Logronio, Maya F. Kotturi, Won Seog Kim, Philippe Armand, Chan Y. Cheah, Ajay K. Gopal, Ian W. Flinn, Gareth P. Gregory, Matthew J. Matasar, Loretta J. Nastoupil, Catherine S. Diefenbach, Sung-Soo Yoon, Matthew Ku, Ibrahim Qazi, Maya K. Leabman, Iris Sison, Bruce A. Keyt, Chris H. Takimoto, Thomas J. Manley, and Elizabeth L. Budde
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
21. Molecular Profiling across Lymphoma Subtypes Using MSK-Impact Next Generation Sequencing
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Connie Lee Batlevi, Esther Drill, Michelle Okwali, Ryan Ptashkin, Philip C Caron, Zachary D. Epstein-Peterson, Lorenzo Falchi, Audrey Hamilton, Paul A. Hamlin, Steven M. Horwitz, Andrew M. Intlekofer, William T. Johnson, Niloufer Khan, Anita Kumar, Jennifer Kimberly Lue, Matthew J. Matasar, Alison J. Moskowitz, Ariela Noy, Colette Owens, Maria Lia Palomba, David J. Straus, Santosha Vardhana, Andrew D. Zelenetz, Maria E. Arcila, Ahmet Dogan, Venkatraman Seshan, Gilles Salles, Ahmet Zehir, and Anas Younes
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
22. Immune Signature of Pembrolizumab Plus Gemcitabine, Vinorelbine, and Liposomal Doxorubicin As Second-Line Therapy for Relapsed or Refractory Classical Hodgkin Lymphoma
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Beatriz Wills, Nivetha Ganesan, Gunjan L. Shah, Phillip Wong, Kimon V. Argyropoulos, Filiz Sen, Ahmet Dogan, David J. Straus, Ariela Noy, Anita Kumar, Heiko Schoder, Laure Michaud, Maria Lia Palomba, Lorenzo Falchi, Oscar B Lahoud, Paul A. Hamlin, Joachim Yahalom, William T. Johnson, Andrew D. Zelenetz, Andrew M. Intlekofer, Colette Owens, Connie Lee Batlevi, Audrey Hamilton, Philip C Caron, Steven M. Horwitz, Natasha Galasso, Helen Hancock, Theresa Davey, Alayna Santarosa, Leslie Perez, Charisse Capadona, Brittney Munayirji, Matthew J. Matasar, Georgios Pongas, Ellie Casper, Gilles Salles, Craig H. Moskowitz, Santosha Vardhana, and Alison J. Moskowitz
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
23. Population Pharmacokinetics and Exposure-Response Analyses from Phase I-III Studies Support Copanlisib Dose Selection in Relapsed Indolent Non-Hodgkin Lymphoma
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Jonathan Moss, Dirk Garmann, Rupert Austin, Florian Hiemeyer, Matthew J. Matasar, Pier Luigi Zinzani, Vita Beckert, Lidia Mongay Soler, Barrett H. Childs, and Peter N. Morcos
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
24. Polatuzumab Vedotin Combined with R-ICE (PolaR-ICE) As Second-Line Therapy in Relapsed/Refractory Diffuse Large B-Cell Lymphoma
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Alex F. Herrera, Lu Chen, Jennifer L. Crombie, Jonathon B. Cohen, Ranjana H. Advani, Ann S. LaCasce, Leslie L. Popplewell, Sandrine Puverel, Lacolle Peters, Shari Daniels, James Godfrey, Geoffrey Shouse, Matthew Mei, Swetha Kambhampati, L. Elizabeth Budde, Liana Nikolaenko, Steven T. Rosen, Larry W. Kwak, Stephen J Forman, and Matthew J. Matasar
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
25. Characterization of a Large Cohort of Patients with Nodal Marginal Zone Lymphoma Shows Prolonged Survival, Time-to-Treatment, and Time-to-Transformation
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Robert Stuver, Esther Drill, David Qualls, Michelle Okwali, Connie Lee Batlevi, Philip C Caron, Zachary D. Epstein-Peterson, Lorenzo Falchi, Audrey Hamilton, Paul A. Hamlin, Steven M. Horwitz, Andrew M. Intlekofer, William T. Johnson, Niloufer Khan, Oscar B Lahoud, Jennifer Kimberly Lue, Matthew J. Matasar, Alison J. Moskowitz, Ariela Noy, M.Lia Palomba, Santosha Vardhana, Andrew D. Zelenetz, Gilles Salles, and David J. Straus
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
26. Reaching beyond maximum grade: progress and future directions for modernising the assessment and reporting of adverse events in haematological malignancies
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Gita Thanarajasingam, Lori M Minasian, Vishal Bhatnagar, Franco Cavalli, R Angelo De Claro, Amylou C Dueck, Tarec C El-Galaly, Neil Everest, Jan Geissler, Christian Gisselbrecht, Nicole Gormley, John Gribben, Mary Horowitz, S Percy Ivy, Caron A Jacobson, Armand Keating, Paul G Kluetz, Yok Lam Kwong, Richard F Little, Matthew J Matasar, Maria-Victoria Mateos, Kristen McCullough, Robert S Miller, Mohamad Mohty, Philippe Moreau, Lindsay M Morton, Sumimasa Nagai, Abhilasha Nair, Loretta Nastoupil, Kaye Robertson, Surbhi Sidana, Karin E Smedby, Pieter Sonneveld, Kyriaki Tzogani, Flora E van Leeuwen, Galina Velikova, Diego Villa, John R Wingard, John F Seymour, and Thomas M Habermann
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SDG 3 - Good Health and Well-being ,Hematologic Neoplasms ,Neoplasms ,Humans ,Antineoplastic Agents ,Hematology ,Article ,Hematologic Neoplasms/complications - Abstract
Remarkable improvements in outcomes for many haematological malignancies have been driven primarily by a proliferation of novel therapeutics over the past two decades. Targeted agents, immune and cellular therapies, and combination regimens have adverse event profiles distinct from conventional finite cytotoxic chemotherapies. In 2018, a Commission comprising patient advocates, clinicians, clinical investigators, regulators, biostatisticians, and pharmacists representing a broad range of academic and clinical cancer expertise examined issues of adverse event evaluation in the context of both newer and existing therapies for haematological cancers. The Commission proposed immediate actions and long-term solutions in the current processes in adverse event assessment, patient-reported outcomes in haematological malignancies, toxicities in cellular therapies, long-term toxicity and survivorship in haematological malignancies, issues in regulatory approval from an international perspective, and toxicity reporting in haematological malignancies and the real-world setting. In this follow-up report, the Commission describes progress that has been made in these areas since the initial report.
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- 2022
27. Supplemental Figure 4 from Phase I/Ib Study of the Efficacy and Safety of Buparlisib and Ibrutinib Therapy in MCL, FL, and DLBCL with Serial Cell-Free DNA Monitoring
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Connie Lee Batlevi, Dana W.Y. Tsui, Anas Younes, Heiko Schöder, Venkatraman Seshan, Gilles Salles, Jurgen Rademaker, Andrew D. Zelenetz, Alison Moskowitz, Craig H. Moskowitz, Anita Kumar, Steven M. Horwitz, David Straus, Audrey Hamilton, Pamela Drullinsky, John F. Gerecitano, Matthew J. Matasar, Paul A. Hamlin, Stephanie De Frank, Chelsea Nichols, Reiko Nakajima, Karissa Whiting, Laure Michaud, and Caitlin M. Stewart
- Abstract
Supplemental Figure S4. Progression-free survival Kaplan-Meier curves based on PET and ctDNA parameters. A. PFS based on baseline SUV categorized into lower and higher than median. B. PFS based on baseline tumor glycolysis level lower or higher than median. C. PFS based on baseline metabolic tumor volume (MTV) lower or higher than median.
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- 2023
28. Supplemental Figure 3 from Phase I/Ib Study of the Efficacy and Safety of Buparlisib and Ibrutinib Therapy in MCL, FL, and DLBCL with Serial Cell-Free DNA Monitoring
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Connie Lee Batlevi, Dana W.Y. Tsui, Anas Younes, Heiko Schöder, Venkatraman Seshan, Gilles Salles, Jurgen Rademaker, Andrew D. Zelenetz, Alison Moskowitz, Craig H. Moskowitz, Anita Kumar, Steven M. Horwitz, David Straus, Audrey Hamilton, Pamela Drullinsky, John F. Gerecitano, Matthew J. Matasar, Paul A. Hamlin, Stephanie De Frank, Chelsea Nichols, Reiko Nakajima, Karissa Whiting, Laure Michaud, and Caitlin M. Stewart
- Abstract
Supplemental Figure S3. A. Waterfall plot based on RECIL criteria. RECIL introduces the minimal response category which is a 10-30% reduction in the sum of longest diameters of target lesions. B. Event-free survival Kaplan-Meier curve.
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- 2023
29. Supplementary Figure S1 from The PARP Inhibitor Veliparib Can Be Safely Added to Bendamustine and Rituximab and Has Preliminary Evidence of Activity in B-Cell Lymphoma
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John F. Gerecitano, Nishant Mishra, Fallon France, Thu O. Dang, Christine Jarjies, Richard F. Little, Alice Chen, Zhigang Zhang, Brian Kiesel, Jan H. Beumer, Alan L. Ho, Richard D. Carvajal, Devika Gajria, Matthew G. Fury, Martin H. Voss, David M. Hyman, Mrinal M. Gounder, Jason A. Konner, Carol S. Portlock, Steven M. Horwitz, Matthew J. Matasar, Anas Younes, Alison J. Moskowitz, David J. Straus, Ariela Noy, Paul A. Hamlin, M. Lia Palomba, Craig H. Moskowitz, Andrew D. Zelenetz, and Jacob D. Soumerai
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CONSORT Diagram.
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- 2023
30. Supplementary Figure Legends from The PARP Inhibitor Veliparib Can Be Safely Added to Bendamustine and Rituximab and Has Preliminary Evidence of Activity in B-Cell Lymphoma
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John F. Gerecitano, Nishant Mishra, Fallon France, Thu O. Dang, Christine Jarjies, Richard F. Little, Alice Chen, Zhigang Zhang, Brian Kiesel, Jan H. Beumer, Alan L. Ho, Richard D. Carvajal, Devika Gajria, Matthew G. Fury, Martin H. Voss, David M. Hyman, Mrinal M. Gounder, Jason A. Konner, Carol S. Portlock, Steven M. Horwitz, Matthew J. Matasar, Anas Younes, Alison J. Moskowitz, David J. Straus, Ariela Noy, Paul A. Hamlin, M. Lia Palomba, Craig H. Moskowitz, Andrew D. Zelenetz, and Jacob D. Soumerai
- Abstract
Supplementary Figure Legends
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- 2023
31. Supplemental Figure 2 from Phase I/Ib Study of the Efficacy and Safety of Buparlisib and Ibrutinib Therapy in MCL, FL, and DLBCL with Serial Cell-Free DNA Monitoring
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Connie Lee Batlevi, Dana W.Y. Tsui, Anas Younes, Heiko Schöder, Venkatraman Seshan, Gilles Salles, Jurgen Rademaker, Andrew D. Zelenetz, Alison Moskowitz, Craig H. Moskowitz, Anita Kumar, Steven M. Horwitz, David Straus, Audrey Hamilton, Pamela Drullinsky, John F. Gerecitano, Matthew J. Matasar, Paul A. Hamlin, Stephanie De Frank, Chelsea Nichols, Reiko Nakajima, Karissa Whiting, Laure Michaud, and Caitlin M. Stewart
- Abstract
Supplemental Figure S2. A. Comparison of treatment-related and -unrelated adverse events occurring in >10% of evaluable patients.
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- 2023
32. Data from The PARP Inhibitor Veliparib Can Be Safely Added to Bendamustine and Rituximab and Has Preliminary Evidence of Activity in B-Cell Lymphoma
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John F. Gerecitano, Nishant Mishra, Fallon France, Thu O. Dang, Christine Jarjies, Richard F. Little, Alice Chen, Zhigang Zhang, Brian Kiesel, Jan H. Beumer, Alan L. Ho, Richard D. Carvajal, Devika Gajria, Matthew G. Fury, Martin H. Voss, David M. Hyman, Mrinal M. Gounder, Jason A. Konner, Carol S. Portlock, Steven M. Horwitz, Matthew J. Matasar, Anas Younes, Alison J. Moskowitz, David J. Straus, Ariela Noy, Paul A. Hamlin, M. Lia Palomba, Craig H. Moskowitz, Andrew D. Zelenetz, and Jacob D. Soumerai
- Abstract
Purpose: The PARP inhibitor veliparib enhances the cytotoxicity of alkylating agents. This phase I study evaluated veliparib with the bifunctional alkylator bendamustine (VB) in patients with relapsed/refractory lymphoma, multiple myeloma, and solid malignancies, with a cohort expansion of VB with rituximab (VBR) in patients with B-cell lymphomas.Experimental Design: This dose-escalation study evaluated safety, pharmacokinetics, and preliminary efficacy of veliparib (20–400 mg twice a day, days 1–7 of 28-day cycle) and bendamustine (70 and 90 mg/m2 intravenously, days 1 and 2). A cohort expansion was conducted, which combined veliparib and bendamustine at the maximum tolerated dose (MTD) with rituximab (375 mg/m2, day 1) in patients with B-cell lymphomas. Thirty-four patients were treated in seven dose-escalation cohorts and seven patients in the dose-expansion cohort.Results: The MTD was veliparib 300 mg twice daily plus bendamustine 90 mg/m2. Dose-limiting toxicities (DLT) were anemia, nausea, hypertension, and hyperhidrosis. Grade ≥3 toxicities included lymphopenia (87.8%), anemia (19.5%), neutropenia (12.2%), thrombocytopenia (9.8%), leukopenia (9.8%), nausea (7.3%), and hypophosphatemia (7.3%). Apparent veliparib clearance was slightly lower than previously reported. Of 14 patients with lymphoma evaluable for response, five of seven (71%) on VB and six of seven (86%) on VBR achieved objective response. One patient with multiple myeloma achieved partial response.Conclusions: VB and VBR were generally well-tolerated. VBR had preliminary clinical activity in patients with B-cell lymphoma, which warrants further investigation in a phase II trial. This trial was registered at www.clinicaltrials.gov as NCT01326702. Clin Cancer Res; 23(15); 4119–26. ©2017 AACR.
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- 2023
33. Supplemental Figure 1 from Phase I/Ib Study of the Efficacy and Safety of Buparlisib and Ibrutinib Therapy in MCL, FL, and DLBCL with Serial Cell-Free DNA Monitoring
- Author
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Connie Lee Batlevi, Dana W.Y. Tsui, Anas Younes, Heiko Schöder, Venkatraman Seshan, Gilles Salles, Jurgen Rademaker, Andrew D. Zelenetz, Alison Moskowitz, Craig H. Moskowitz, Anita Kumar, Steven M. Horwitz, David Straus, Audrey Hamilton, Pamela Drullinsky, John F. Gerecitano, Matthew J. Matasar, Paul A. Hamlin, Stephanie De Frank, Chelsea Nichols, Reiko Nakajima, Karissa Whiting, Laure Michaud, and Caitlin M. Stewart
- Abstract
Supplemental Figure S1. Dosing of patients on study. A. MCL cohort. B. FL cohort. C. DLBCL cohort.
- Published
- 2023
34. Single-Agent Mosunetuzumab Shows Durable Complete Responses in Patients With Relapsed or Refractory B-Cell Lymphomas: Phase I Dose-Escalation Study
- Author
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Lihua E. Budde, Sarit Assouline, Laurie H. Sehn, Stephen J. Schuster, Sung-Soo Yoon, Dok Hyun Yoon, Matthew J. Matasar, Francesc Bosch, Won Seog Kim, Loretta J. Nastoupil, Ian W. Flinn, Mazyar Shadman, Catherine Diefenbach, Carol O'Hear, Huang Huang, Antonia Kwan, Chi-Chung Li, Emily C. Piccione, Michael C. Wei, Shen Yin, Nancy L. Bartlett, Institut Català de la Salut, [Budde LE] City of Hope National Medical Center, Duarte, CA. [Assouline S] Jewish General Hospital and McGill University, Montreal, Quebec, Canada. [Sehn LH] BC Cancer Centre for Lymphoid Cancer and The University of British Columbia, Vancouver, British Columbia, Canada. [Schuster SJ] Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA. [Yoon SS] Seoul National University Hospital, Seoul, South Korea. [Yoon DH] Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. [Bosch F] Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
- Subjects
Adult ,Male ,Canada ,Cancer Research ,Lymphoma, B-Cell ,Time Factors ,Cèl·lules B - Tumors - Immunoteràpia ,Neoplasms::Neoplasms by Histologic Type::Lymphoma::Lymphoma, Non-Hodgkin::Lymphoma, B-Cell [DISEASES] ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,neoplasias::neoplasias por tipo histológico::linfoma::linfoma no Hodgkin::linfoma de células B [ENFERMEDADES] ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] ,Drug Administration Schedule ,Young Adult ,Antineoplastic Agents, Immunological ,Antibodies, Bispecific ,Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents::Antineoplastic Agents, Immunological [CHEMICALS AND DRUGS] ,Humans ,Aged ,Aged, 80 and over ,Otros calificadores::Otros calificadores::/administración & dosificación [Otros calificadores] ,Remission Induction ,diagnóstico::pronóstico::resultado del tratamiento [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Middle Aged ,Diagnosis::Prognosis::Treatment Outcome [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,Posologia ,United States ,Treatment Outcome ,Oncology ,Avaluació de resultats (Assistència sanitària) ,Other subheadings::Other subheadings::/administration & dosage [Other subheadings] ,Administration, Intravenous ,Female ,acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos::inmunoterapia antineoplásica [COMPUESTOS QUÍMICOS Y DROGAS] - Abstract
PURPOSE Mosunetuzumab is a bispecific antibody targeting CD20 and CD3 that redirects T cells to engage and eliminate malignant B cells and is being developed for relapsed or refractory (R/R) B-cell non-Hodgkin lymphomas (B-NHLs). METHODS This first-in-human trial (ClinicalTrials.gov identifier: NCT02500407 ) evaluated the safety and tolerability and efficacy of mosunetuzumab in patients with R/R B-NHL and established the recommended phase II dose. Data from dose escalation are presented. Single-agent mosunetuzumab was administered intravenously in 3-week cycles, at full dose in cycle 1 day 1 (group A) or with ascending (step-up) doses during cycle 1 on days 1, 8, and 15 (group B), for eight or 17 cycles on the basis of tumor response. RESULTS Two hundred thirty patients were enrolled. Doses up to 2.8 mg and 60 mg were assessed in groups A and B, respectively; maximum tolerated dose was not exceeded. In group B (n = 197), common adverse events (≥ 20% of patients) were neutropenia (28.4%), cytokine release syndrome (27.4%), hypophosphatemia (23.4%), fatigue (22.8%), and diarrhea (21.8%). Cytokine release syndrome was mostly low-grade (grade ≥ 3: 1.0%) and mainly confined to cycle 1. Across the doses investigated (group B), best overall response rates were 34.9% and 66.2% in patients with aggressive and indolent B-NHL, respectively, and complete response rates were 19.4% and 48.5%. Among patients with a complete response, the median duration of response was 22.8 months (95% CI, 7.6 to not estimable) and 20.4 (95% CI, 16 to not estimable) in patients with aggressive and indolent B-NHL, respectively. CONCLUSION Mosunetuzumab, administered with step-up dosing, has a manageable safety profile and induces durable complete responses in R/R B-NHL. The expansion stage of the study is ongoing at the dose level of 1/2/60/60/30 mg selected for further study.
- Published
- 2022
35. Phase I/Ib Study of the Efficacy and Safety of Buparlisib and Ibrutinib Therapy in MCL, FL, and DLBCL with Serial Cell-Free DNA Monitoring
- Author
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Audrey Hamilton, Heiko Schöder, Karissa Whiting, Reiko Nakajima, Dana W.Y. Tsui, Steven M. Horwitz, Alison J. Moskowitz, Stephanie De Frank, Caitlin Stewart, Craig H. Moskowitz, John F. Gerecitano, Laure Michaud, Andrew D. Zelenetz, Venkatraman E. Seshan, Paul A. Hamlin, Connie Lee Batlevi, Pamela Drullinsky, David J. Straus, Jürgen Rademaker, Gilles Salles, Chelsea Nichols, Anita Kumar, Matthew J. Matasar, and Anas Younes
- Subjects
Adult ,Oncology ,Cancer Research ,medicine.medical_specialty ,Morpholines ,Buparlisib ,Follicular lymphoma ,Aminopyridines ,Lymphoma, Mantle-Cell ,Article ,Phosphatidylinositol 3-Kinases ,chemistry.chemical_compound ,Piperidines ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Bruton's tyrosine kinase ,Adverse effect ,biology ,business.industry ,Adenine ,medicine.disease ,Rash ,Lymphoma ,Pyrimidines ,chemistry ,Ibrutinib ,biology.protein ,Pyrazoles ,Mantle cell lymphoma ,Lymphoma, Large B-Cell, Diffuse ,medicine.symptom ,business ,Cell-Free Nucleic Acids - Abstract
Purpose: Activation of Bruton tyrosine kinase (BTK) and phosphatidylinositol-3-kinase (PI3K) represent parallel, synergistic pathways in lymphoma pathogenesis. As predominant PI3Kδ inhibition is a possible mechanism of tumor escape, we proposed a clinical trial of dual BTK and pan-PI3K inhibition. Patients and Methods: We conducted a single-center phase I/Ib trial combining a BTK inhibitor (ibrutinib) and a pan-PI3K inhibitor (buparlisib) in 37 patients with relapsed/refractory (R/R) B-cell lymphoma. Buparlisib and ibrutinib were administered orally, once daily in 28-day cycles until progression or unacceptable toxicity. The clinical trial is registered with clinicaltrials.gov, NCT02756247. Results: Patients with mantle cell lymphoma (MCL) receiving the combination had a 94% overall response rate (ORR) and 33-month median progression-free survival; ORR of 31% and 20% were observed in patients with diffuse large B-cell lymphoma and follicular lymphoma, respectively. The maximum tolerated dose was ibrutinib 560 mg plus buparlisib 100 mg and the recommended phase II dose was ibrutinib 560 mg plus buparlisib 80 mg. The most common grade 3 adverse events were rash/pruritis/dermatitis (19%), diarrhea (11%), hyperglycemia (11%), and hypertension (11%). All grade mood disturbances ranging from anxiety, depression, to agitation were observed in 22% of patients. Results from serial monitoring of cell-free DNA samples corresponded to radiographic resolution of disease and tracked the emergence of mutations known to promote BTK inhibitor resistance. Conclusions: BTK and pan-PI3K inhibition in mantle cell lymphoma demonstrates a promising efficacy signal. Addition of BCL2 inhibitors to a BTK and pan-PI3K combination remain suitable for further development in mantle cell lymphoma.
- Published
- 2022
36. Polatuzumab vedotin plus bendamustine and rituximab in relapsed/refractory DLBCL: survival update and new extension cohort data
- Author
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Mark P. Hertzberg, Jamie Hirata, Gilles Salles, Laurie H. Sehn, Muhit Ozcan, Grace Ku, Christopher R. Flowers, Alex F. Herrera, Andrew McMillan, Tae Min Kim, Stephen Opat, Lisa Musick, Yi Meng Chang, Violaine Safar, Matthew J. Matasar, and Sarit Assouline
- Subjects
Bendamustine ,medicine.medical_specialty ,Immunoconjugates ,Clinical Trials and Observations ,Gastroenterology ,Refractory ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Clinical endpoint ,Medicine ,Bendamustine Hydrochloride ,Humans ,business.industry ,Hazard ratio ,Antibodies, Monoclonal ,Hematology ,Confidence interval ,Polatuzumab vedotin ,Cohort ,bacteria ,Rituximab ,business ,medicine.drug - Abstract
Key Points Consistent with previous results, pola + BR has a tolerable safety profile.The survival benefit of pola + BR vs BR persists with longer follow-up; efficacy in the pola + BR extension and randomized arms was similar., Visual Abstract, Polatuzumab vedotin plus bendamustine and rituximab (pola + BR) received regulatory approvals for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) based on primary results from the randomized arms of the GO29365 study. After the randomized phase, 106 additional patients received pola + BR in a single-arm extension cohort. We report updated results from the randomized arms and results of the extension cohort. In this phase 1b/2 study, patients with R/R DLBCL who were transplant ineligible received up to six 21-day cycles of pola + BR or BR. The primary end point of the randomized arms was the complete response (CR) rate at end of treatment. Primary objectives of the extension cohort were safety, pharmacokinetic profile, and efficacy of pola + BR. As of 7 July 2020, a total of 192 patients with R/R DLBCL were enrolled in the pola + BR cohort (n = 152 [safety run-in, n = 6; randomized, n = 40; extension cohort, n = 106]) or the BR cohort (n = 40). Significant survival benefit with pola + BR vs BR persisted in the randomized arms (median progression-free survival, 9.2 vs 3.7 months [hazard ratio, 0.39; 95% confidence interval, 0.23-0.66]; median overall survival, 12.4 vs 4.7 months [hazard ratio, 0.42; 95% confidence interval, 0.24-0.72]). In the extension cohort, the independent review committee–assessed objective response rate was 41.5%, and the CR rate was 38.7%; median independent review committee–assessed progression-free survival and overall survival were 6.6 months and 12.5 months, respectively. No new safety signals with pola + BR were identified. Pola + BR is an effective treatment option for patients with R/R DLBCL, with a well-characterized and manageable safety profile. This trial was registered at www.clinicaltrials.gov as #NCT02257567.
- Published
- 2022
37. Translating the Biology of Diffuse Large B-cell Lymphoma Into Treatment
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Alexey V Danilov, Massimo Magagnoli, and Matthew J Matasar
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Cancer Research ,Oncology ,Humans ,Lymphoma, Large B-Cell, Diffuse ,Precision Medicine ,Biology - Abstract
Diffuse large B-cell lymphoma (DLBCL) is characterized by clinical and molecular heterogeneity; however, this heterogeneity is rarely taken into account by standard-of-care treatment approaches. While the disease was traditionally classified based on transcriptome signatures purporting the tumor cell of origin, recent classification systems have further differentiated these subtypes into clusters based on molecular and genetic features. Alongside a better understanding of the biology of the disease and the signaling pathways involved, emerging therapeutic agents may be better aimed at attacking distinct disease subsets. It is hoped that molecular subtyping at diagnosis will allow patients to be allocated to the appropriate treatment that targets their specific disease subtype, thus advancing the promise of precision medicine in lymphoma, an approach that is most needed. For high-risk disease subsets, this is particularly important, and much research is still needed to develop agents effective in this population. Here, we review recent advances in DLBCL biology and how they can be translated into clinical care.
- Published
- 2022
38. Zanubrutinib, obinutuzumab, and venetoclax with minimal residual disease-driven discontinuation in previously untreated patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: a multicentre, single-arm, phase 2 trial
- Author
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Colette Owens, Allison P. Jacob, Jade Ruiters, Sidney Sechio, Audrey Hamilton, Clare Grieve, Puja Chadha, Mikhail Roshal, Tak Takvorian, Daneal Portman, Anthony R. Mato, Krista J Scorsune, Jason Carter, Ahmet Dogan, Lauren Ramos, Ai Ni, Natascha Nolet, Juliana M.L. Biondo, Jane Huang, Ephraim P. Hochberg, Anita Kumar, Stephanie Hughes, Morgan Choma, M. Lia Palomba, Rosalba Martignetti, Ariela Noy, Jeffrey A. Barnes, Meghan C. Thompson, P. Connor Johnson, Jeremy S. Abramson, Connie Lee Batlevi, Julia M Lynch, Qun Wu, Chaya Friedman, Erel Joffe, Joanna Mi, Brianne McGree, Elizabeth Simkins, Venkatraman E. Seshan, Matthew J. Matasar, Kelsey Flaherty, Omar Abdel-Wahab, Lindsey E. Roeker, Andrew D. Zelenetz, Jacob D. Soumerai, and Neena Mahajan
- Subjects
Male ,medicine.medical_specialty ,Neoplasm, Residual ,Population ,Neutropenia ,Antibodies, Monoclonal, Humanized ,Gastroenterology ,chemistry.chemical_compound ,Piperidines ,Obinutuzumab ,hemic and lymphatic diseases ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,education ,Aged ,Sulfonamides ,education.field_of_study ,Venetoclax ,business.industry ,Hematology ,Middle Aged ,Bridged Bicyclo Compounds, Heterocyclic ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,Minimal residual disease ,Lymphoma ,Regimen ,Pyrimidines ,chemistry ,Pyrazoles ,Female ,Mantle cell lymphoma ,business - Abstract
Summary Background We hypothesised that combining zanubrutinib with obinutuzumab and venetoclax (BOVen) as an initial therapy for chronic lymphocytic leukaemia and small lymphocytic lymphoma would lead to high rates of undetectable minimal residual disease (MRD), and we explored MRD as a biomarker for directing treatment duration. Methods This multicenter, investigator-initiated, single-arm, phase 2 trial took place at two two academic medical centres in the USA. Patients were eligible for the primary cohort if they had treatment-naive chronic lymphocytic leukaemia or small lymphocytic lymphoma, required therapy, and were at least 18 years of age with an Eastern Cooperative Oncology Group performance status up to 2. BOVen was administered in 28 day cycles (oral zanubrutinib at 160 mg twice per day starting in cycle 1 on day 1; intravenous obinutuzumab at 1000 mg on day 1 [split over day 1 with 100 mg and day 2 with 900 mg for an absolute lymphocyte count >25 000 cells per μL or lymph nodes >5 cm in diameter], day 8, and day 15 of cycle 1, and day 1 of cycles 2–8; and oral venetoclax ramp up to 400 mg per day starting in cycle 3 on day 1) and discontinued after 8–24 cycles when prespecified undetectable MRD criteria were met in the peripheral blood and bone marrow. The primary endpoint was the proportion of patients that reached undetectable MRD in both the peripheral blood and bone marrow (flow cytometry cutoff less than one chronic lymphocytic leukaemia cell per 10 000 leukocytes [ clinicaltrials.gov ( NCT03824483 ). The primary cohort is closed to recruitment, and recruitment continues in the TP53-mutated mantle cell lymphoma cohort. Findings Between March 14, 2019, and Oct 10, 2019, 47 patients were screened for eligibility, and 39 patients were enrolled and treated. Median age was 62 years (IQR 52–70) with 30 (77%) of 39 male participants and nine (23%) of 39 female participants. 28 (72%) of 39 patients had unmutated immunoglobulin heavy-chain variable-region and five (13%) of 39 had 17p deletion or TP53 mutation. After a median follow-up of 25·8 months (IQR 24·0–27·3), 33 (89%) of 37 patients (95% CI 75–97) had undetectable MRD in both blood and bone marrow, meeting the prespecified undetectable MRD criteria to stop therapy after a median of ten cycles (IQR 8–12), which includes two cycles of zanubrutinib and obinutuzumab before starting venetoclax. After median surveillance after treatment of 15·8 months (IQR 13·0–18·6), 31 (94%) of 33 patients had undetectable MRD. The most common adverse events were thrombocytopenia (23 [59%] of 39), fatigue (21 [54%]), neutropenia (20 [51%]), and bruising (20 [51%]), and the most common adverse event at grade 3 or worse was neutropenia (seven [18%]) in the intention-to-treat population. One death occurred in a patient with intracranial haemorrhage on day 1 of cycle 1 after initiating intravenous heparin for pulmonary emboli. Interpretation BOVen was well tolerated and met its primary endpoint, with 33 (89%) of 37 previously untreated patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma reaching undetectable MRD in both peripheral blood and bone marrow despite a median treatment duration of only 10 months, owing to our undetectable MRD-driven treatment discontinuation design. These data support further evaluation of the BOVen regimen in chronic lymphocytic leukaemia and small lymphocytic lymphoma with treatment duration guided by early MRD response kinetics. Funding Beigene, Genentech (Roche), Grais-Cutler Fund, Lymphoma Research Fund, Lymphoma Research Foundation, American Cancer Society, Farmer Family Foundation, and the National Instititutes of Health and National Cancer Institute.
- Published
- 2021
39. Successful implementation of outpatient R ± DHAX (rituximab, dexamethasone, oxaliplatin, cytarabine) for select patients with lymphoma: a single-center experience
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Anas Younes, Joy C. Jarrett, Anita Kumar, Tara A. Duggan, Alison J. Moskowitz, Megan H. Leary, Ariela Noy, Colette Owens, Lorenzo Falchi, Gottfried von Keudell, Michael J Buege, Brianne N. Dixon, Paul A. Hamlin, Phuong H. Dao, Matthew J. Matasar, Andrew D. Zelenetz, Terry K. Pak, Philip Caron, and Audrey Hamilton
- Subjects
Cancer Research ,medicine.medical_specialty ,Lymphoma ,Hospital bed ,medicine.medical_treatment ,Single Center ,Dexamethasone ,Patient satisfaction ,Antineoplastic Combined Chemotherapy Protocols ,Outpatients ,medicine ,Humans ,Adverse effect ,Chemotherapy ,business.industry ,Cytarabine ,Hematology ,Oxaliplatin ,Oncology ,Emergency medicine ,Rituximab ,business ,medicine.drug - Abstract
R ± DHAX has been traditionally administered to inpatient due to the timing of chemotherapy administration and the perceived need for close monitoring of adverse effects. To administer R ± DHAX outpatient, a multidisciplinary task force created clinical and educational guidelines which were implemented through two phases: pilot and expansion. The pilot program determined the feasibility of transitioning R ± DHAX outpatient at a single infusion site. The expansion phase led to a service-wide implementation across all outpatient sites. A total of 40 patients were included, of which 23 patients completed all cycles, outpatient, 12 transitioned inpatient to outpatient administration, and 5 transitioned outpatient to inpatient administration. The success rate of outpatient R ± DHAX administration was 90% (36 patients successfully completed outpatient administration/40 total patients). No cytarabine-related cerebellar or ophthalmic toxicity was reported. Outpatient R ± DHAX saved 192 hospital days. R ± DHAX could be successfully administered outpatient with minimal safety concerns and reduced hospital bed utilization.
- Published
- 2021
40. Long-term outcomes of patients with limited-stage ocular adnexal DLBCL treated with combined modality therapy in the rituximab era
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David Qualls, Brandon S. Imber, Michelle Okwali, Paul A. Hamlin, Anita Kumar, Oscar B. Lahoud, Matthew J. Matasar, Ariela Noy, Colette Owens, Andrew D. Zelenetz, Victoria S. North, Heiko Schöder, Ahmet Dogan, Gilles Salles, Joachim Yahalom, and Lorenzo Falchi
- Subjects
Hematology - Published
- 2022
41. Brentuximab Vedotin Combined With Chemotherapy in Patients With Newly Diagnosed Early-Stage, Unfavorable-Risk Hodgkin Lymphoma
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Steven M. Horwitz, Philip Caron, Pamela Drullinsky, Joachim Yahalom, Matthew J. Matasar, Connie Lee Batlevi, Anita Kumar, Esther Drill, A. Joseph, Audrey Hamilton, Ranjana H. Advani, Richard T. Hoppe, Heiko Schöder, Jonathan W. Friedberg, Joanna C. Yang, Elizabeth Budde, Paul A. Hamlin, Louis S. Constine, Maria Lia Palomba, Craig H. Moskowitz, Anas Younes, Shreya Vemuri, Andrew D. Zelenetz, Niloufer Khan, Clare Grieve, David J. Straus, Carla Casulo, Leana Laraque, Alison J. Moskowitz, Paul M. Barr, Ariela Noy, and S.V. Dandapani
- Subjects
Adult ,Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Time Factors ,Adolescent ,medicine.medical_treatment ,Pilot Projects ,Newly diagnosed ,Vinblastine ,Risk Assessment ,Young Adult ,Antineoplastic Agents, Immunological ,Risk Factors ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,In patient ,Stage (cooking) ,Brentuximab vedotin ,Adverse effect ,Neoplasm Staging ,Brentuximab Vedotin ,Chemotherapy ,business.industry ,Chemoradiotherapy ,Middle Aged ,Hodgkin Disease ,Progression-Free Survival ,United States ,Dacarbazine ,Doxorubicin ,Positron-Emission Tomography ,Cohort ,Disease Progression ,Hodgkin lymphoma ,Female ,business ,medicine.drug - Abstract
PURPOSE To improve curability and limit long-term adverse effects for newly diagnosed early-stage (ES), unfavorable-risk Hodgkin lymphoma. METHODS In this multicenter study with four sequential cohorts, patients received four cycles of brentuximab vedotin (BV) and doxorubicin, vinblastine, and dacarbazine (AVD). If positron emission tomography (PET)-4–negative, patients received 30-Gy involved-site radiotherapy in cohort 1, 20-Gy involved-site radiotherapy in cohort 2, 30-Gy consolidation-volume radiotherapy in cohort 3, and no radiotherapy in cohort 4. Eligible patients had ES, unfavorable-risk disease. Bulk disease defined by Memorial Sloan Kettering criteria (> 7 cm in maximal transverse or coronal diameter on computed tomography) was not required for cohorts 1 and 2 but was for cohorts 3 and 4. The primary end point was to evaluate safety for cohort 1 and to evaluate complete response rate by PET for cohorts 2-4. RESULTS Of the 117 patients enrolled, 116 completed chemotherapy, with the median age of 32 years: 50% men, 98% stage II, 86% Memorial Sloan Kettering–defined disease bulk, 27% traditional bulk (> 10 cm), 52% elevated erythrocyte sedimentation rate, 21% extranodal involvement, and 56% > 2 involved lymph node sites. The complete response rate in cohorts 1-4 was 93%, 100%, 93%, and 97%, respectively. With median follow-up of 3.8 years (5.9, 4.5, 2.5, and 2.2 years for cohorts 1-4), the overall 2-year progression-free and overall survival were 94% and 99%, respectively. In cohorts 1-4, the 2-year progression-free survival was 93%, 97%, 90%, and 97%, respectively. Adverse events included neutropenia (44%), febrile neutropenia (8%), and peripheral neuropathy (54%), which was largely reversible. CONCLUSION BV + AVD × four cycles is a highly active and well-tolerated treatment program for ES, unfavorable-risk Hodgkin lymphoma, including bulky disease. The efficacy of BV + AVD supports the safe reduction or elimination of consolidative radiation among PET-4–negative patients.
- Published
- 2021
42. Toxicities of high-dose chemotherapy and autologous hematopoietic cell transplantation in older patients with lymphoma
- Author
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Miguel-Angel Perales, Molly Maloy, Sean M. Devlin, Erica Petrlik, Matthew J. Matasar, Craig H. Moskowitz, Esperanza B. Papadopoulos, Gunjan L. Shah, Josel D. Ruiz, Michael Scordo, Parastoo B. Dahi, Craig S. Sauter, Carlos Rondon-Clavo, Jasme Lee, Roni Tamari, Ann A. Jakubowski, Paul A. Hamlin, and Sergio Giralt
- Subjects
Melphalan ,Transplantation ,medicine.medical_specialty ,Chemotherapy ,Carmustine ,business.industry ,medicine.medical_treatment ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,Hematology ,Hematopoietic stem cell transplantation ,medicine.disease ,Transplantation, Autologous ,Chemotherapy regimen ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,business ,Febrile neutropenia ,Aged ,medicine.drug - Abstract
High-dose chemotherapy and autologous hematopoietic cell transplantation is an effective consolidation therapy in lymphoma; however, its use in elderly patients has been limited because of concerns for greater toxicity in this group. We investigated the toxicities of carmustine, etoposide, cytarabine, and melphalan (BEAM) and autologous hematopoietic cell transplantation (AHCT) in 346 patients in 2 age groups: 279 patients aged 60 to 69 years and 67 patients aged ≥70 years. The majority developed severe toxicities; the most common were febrile neutropenia, gastrointestinal, infections, and cardiovascular. Older patients were at higher risk for grade ≥3 cardiovascular toxicities (hazard ratio [HR], 3.36; 95% confidence interval [CI], 2.25-5.00; P < .001) and skin toxicities (HR, 2.45; 95% CI, 1.08-5.54, P = .032). In the older group, nonrelapse mortality at 100 days and at 2 years was 2.99% (95% CI, 0.55-9.32) and 6.2% (95% CI, 1.97-13.95), respectively, vs 1.79% (95% CI, 0.68-3.92) and 2.91% (95% CI, 1.37-5.42), respectively, in the younger group. When adjusting for the number of grade ≥3 toxicities within the first 100 days, older patients had a 1.71-fold (95% CI, 1.08-2.71) increased risk for progression or death relative to younger patients. Although BEAM followed by AHCT is effective, it is associated with significant organ toxicities, especially in patients aged ≥70 years. Interventions to mitigate toxicities while maintaining efficacy are much needed.
- Published
- 2021
43. LymphGen Classification of Diffuse Large B-Cell Lymphoma in a Cohort of Adolescent and Young Adult (AYA) Patients
- Author
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Angelo Cabal, Menglei Zhu, Manik Uppal, Erel Joffe, Connie Lee Batlevi, Matthew J. Matasar, Michelle Okwali, Ahmet Dogan, Andrew D. Zelenetz, Gilles Salles, and Niloufer Khan
- Subjects
Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
44. Closing the Gap: Implementation of a Novel Interactive Virtual Tumor Board to Improve Expert Knowledge Sharing in Malignant Hematology
- Author
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Jordan Ciuro, Elizabeth Henry, Nadine Housri, Rahul Banerjee, Elizabeth A Brem, Taylor Brooks, Ben A. Derman, Brian T. Hill, Craig C Hofmeister, Matthew A. Lunning, Matthew J. Matasar, Tycel J. Phillips, Sarah C. Rutherford, Saurabh Zanwar, and Lauren E Lee
- Subjects
Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
45. Vitalize Trial: A Phase 2b, Open-Label, Multicenter, Randomized Parallel-Group, Two-Stage, Study of the Novel Immunotherapeutic, Maveropepimut-S, and Pembrolizumab with and without Intermittent Low-Dose Cyclophosphamide, in Subjects with Relapsed/Refractory Diffuse Large B-Cell Lymphoma
- Author
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Matthew J. Matasar, Eric Lee, Sophie Leitch, Melhem Solh, Jennifer Teti, Kabir Mody, Stephan Fiset, and Jeremy Graff
- Subjects
Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
46. Active surveillance of primary extranodal marginal zone lymphoma of bronchus-associated lymphoid tissue
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Esther Drill, Steven M. Horwitz, Carol S. Portlock, Sridevi Rajeeve, Matthew J. Matasar, Anas Younes, Ariela Noy, John F. Gerecitano, Erel Joffe, Yan Leyfman, Craig H. Moskowitz, David J. Straus, Connie Lee Batlevi, Anita Kumar, M. Lia Palomba, Andrew D. Zelenetz, Alison J. Moskowitz, and Paul A. Hamlin
- Subjects
medicine.medical_specialty ,Lymphoid Neoplasia ,Lung ,business.industry ,medicine.medical_treatment ,Cancer ,Bronchi ,Retrospective cohort study ,Lymphoma, B-Cell, Marginal Zone ,Hematology ,Disease ,Immunotherapy ,medicine.disease ,Gastroenterology ,Progression-Free Survival ,Lymphoma ,Lymphatic system ,medicine.anatomical_structure ,Internal medicine ,medicine ,Humans ,Lymph ,Watchful Waiting ,business ,Retrospective Studies - Abstract
Although patients with bronchus-associated lymphoid tissue (BALT) lymphoma show an indolent clinical course, appropriate disease management at diagnosis is not well defined. This study aimed to compare 3 treatment strategies for patients with BALT lymphoma: active surveillance, systemic chemotherapy or immunotherapy at diagnosis, or complete surgical resection at diagnosis. We conducted a retrospective study of all patients with new diagnoses of marginal zone lymphoma (MZL) involving the lung who were treated at the Memorial Sloan Kettering Cancer Center between 1995 and 2017. Primary BALT lymphoma was defined as disease confined to the lungs and adjacent lymph nodes. Active surveillance was defined as a documented observation plan and ≥3 months of follow-up before initiating treatment. Overall survival (OS) and event-free survival (EFS) were compared between treatment groups. We reviewed 200 consecutive patients with MZL involving the lung; 123 met the inclusion criteria and were managed by active surveillance (47%), complete surgical resection (41%), or systemic chemotherapy or immunotherapy (11%). With a median follow-up of >60 months, surgical resection was associated with a superior EFS compared with active surveillance and systemic treatment (6-year EFS: 74% vs 65% vs 62%, respectively; P = .013). Larger lesions and thrombocytopenia were associated with shorter EFS. All groups had excellent OS at 6 years (93%), albeit with a slight superiority for surgical resection (100%) over active surveillance (91%) and systemic treatment (76%) (P = .024). BALT lymphoma is an indolent disease that can often be managed expectantly and not require therapy for many years.
- Published
- 2021
47. Outcomes in patients with DLBCL treated with commercial CAR T cells compared with alternate therapies
- Author
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Michael Scordo, Gunjan L. Shah, Ariela Noy, Andrew D. Zelenetz, Lorenzo Falchi, Sean M. Devlin, Erel Joffe, Gottfried von Keudell, David Sermer, Miguel-Angel Perales, Craig S. Sauter, Alison J. Moskowitz, Paul A. Hamlin, Anas Younes, Caleb Ho, Mari Lynne Silverberg, Aishat Afuye, Jessica Flynn, Audrey Hamilton, Richard J. Lin, Martina Pennisi, Philip Caron, Ildefonso Rodriguez-Rivera, Parastoo B. Dahi, Anita Kumar, M. Lia Palomba, Joachim Yahalom, Matthew J. Matasar, Colette Owens, Connie L Batlevi, Steven M. Horwitz, and David J. Straus
- Subjects
Oncology ,medicine.medical_specialty ,education.field_of_study ,Clinical Trials and Observations ,business.industry ,T-Lymphocytes ,Antigens, CD19 ,Population ,Retrospective cohort study ,Hematology ,medicine.disease ,Single Center ,Lymphoma ,Prior Therapy ,Refractory ,Internal medicine ,Cohort ,medicine ,Humans ,Lymphoma, Large B-Cell, Diffuse ,Prospective Studies ,Prospective cohort study ,education ,business ,Retrospective Studies - Abstract
The prognosis of patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) is poor. Chimeric antigen receptor (CAR) T-cell therapy has been approved for R/R DLBCL after 2 prior lines of therapy based on data from single-arm phase 2 trials, with complete responses (CRs) in 40% to 60% of patients. However, a direct comparison with other treatments is not available and, moreover, its true efficacy in real-world patients is unknown. In this single center, retrospective, observational study of 215 patients, we compared outcomes in patients treated with CAR T-cell therapy (n = 69) with a historical population treated with alternate therapies (n = 146). Patients treated with CAR T cell vs alternate therapies demonstrated a CR rate of 52% vs 22% (P < .001), median progression-free survival (PFS) of 5.2 vs 2.3 months (P = .01), and median overall survival (OS) of 19.3 vs 6.5 months (P = .006), and this advantage appeared to persist irrespective of the number of lines of prior therapy. After adjusting for unfavorable pretreatment disease characteristics, superior overall response rate in the CAR T cohort remained significant; however, differences in PFS and OS between cohorts did not. In addition, patients who responded to alternate therapies demonstrated prolonged remissions comparable to those who responded to CAR T therapy. We contend that in select clinical scenarios alternate therapies may be as efficacious as CAR T therapy; thus, additional study is warranted, ideally with randomized prospective trials.
- Published
- 2020
48. Patient preferences for first-line treatment of classical Hodgkin lymphoma: a US survey and discrete choice experiment
- Author
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Niloufer Khan, Ellen E. Korol, Mary He, Mayvis Rebeira, Mehul Dalal, Joseph Feliciano, Matthew J. Matasar, Kerstin Müller, and Rei Tao
- Subjects
Adult ,Cancer Research ,Pediatrics ,medicine.medical_specialty ,Discrete choice experiment ,Choice Behavior ,Article ,03 medical and health sciences ,0302 clinical medicine ,immune system diseases ,Surveys and Questionnaires ,hemic and lymphatic diseases ,Classical Hodgkin lymphoma ,Humans ,Medicine ,In patient ,skin and connective tissue diseases ,business.industry ,Patient Preference ,Hematology ,Hodgkin Disease ,Patient preference ,First line treatment ,Cross-Sectional Studies ,Oncology ,030220 oncology & carcinogenesis ,business ,030215 immunology - Abstract
A cross-sectional online survey, including a discrete choice experiment (DCE), was used to investigate first-line treatment preferences in patients with classical Hodgkin lymphoma (cHL) in the United States; 141 patients (median age 35.0 years) participated. In the DCE, risk of progression at 2 years (progression free survival) had the highest relative importance to patients (31.3%) when considering first-line treatments, followed by 2-year overall survival (OS; 26.9%), on-treatment pulmonary toxicity (23.3%), and on-treatment peripheral neuropathy (18.5%). Marginal rate of substitution analyses demonstrated that a 0.44% and 0.09% increase in 2-year OS was required for patients to accept a 1% increase in the risk of disease progression at 2 years and peripheral neuropathy, respectively. A 2.6% increase in 2-year OS was needed to accept a 7% rather than a 2% risk of pulmonary toxicity. In summary, patients with cHL rated survival attributes as more important than drug-related toxicity when considering first-line treatments.
- Published
- 2020
49. Cancer worry and empathy moderate the effect of a survivorship‐focused intervention on quality of life
- Author
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David W. Kissane, Alan B. Astrow, Matthew J. Matasar, Patricia A. Parker, Carma L. Bylund, Paul B. Jacobsen, Smita C. Banerjee, Steven M. Horwitz, Elizabeth Schofield, Howard Leventhal, and Yuelin Li
- Subjects
Adult ,Male ,medicine.medical_treatment ,media_common.quotation_subject ,Experimental and Cognitive Psychology ,Empathy ,Survivorship ,Anxiety ,Article ,Random Allocation ,03 medical and health sciences ,0302 clinical medicine ,Patient Education as Topic ,Quality of life ,Neoplasms ,Intervention (counseling) ,Survivorship curve ,business.product_line ,Humans ,Medicine ,030212 general & internal medicine ,media_common ,Physician-Patient Relations ,Rehabilitation ,business.industry ,Social Support ,Middle Aged ,Moderation ,Communication skills training ,humanities ,Psychiatry and Mental health ,Oncology ,030220 oncology & carcinogenesis ,Quality of Life ,Female ,Worry ,business ,Clinical psychology - Abstract
OBJECTIVE: This study examined the impact of a survivorship planning consultation (SPC) for patients with Hodgkin’s lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL) on quality of life (QOL). We specifically assessed two potential moderators, cancer worry and perceived empathy, of the intervention effects on QOL. METHODS: This cluster randomized, four-site trial examined the efficacy of a SPC; physicians received communication skills training and applied these skills in a survivorship-focused office visit using a care plan versus a control arm in which physicians were trained to and subsequently provided a time-controlled, manualized Wellness Rehabilitation Consultation (WRC) focused only on discussion of healthy nutrition and exercise. We examined the effect of the intervention on patients’ QOL and examined potential moderators--cancer worry and perceived physician empathy. RESULTS: Forty-two physicians and 198 patients participated. There was no main effect of the intervention on any of the QOL dimensions (ps > 0.10). However, cancer worry was a significant moderator of the effects of the intervention on three QOL domains (physical p=0.04; social p=0.04; spiritual p=.01) and perceived empathy was a significant moderator of QOL (physical p=0.004; psychological p=0.04; social p=0.01). Specifically, the beneficial effects of the intervention were more pronounced among patients who initially reported higher levels of cancer worry and lower levels of physician empathy. CONCLUSIONS: This study identified two factors, perceived empathy and cancer worry, that were found to impact the QOL of patients who participated in this communication-based survivorship intervention.
- Published
- 2020
50. Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma
- Author
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Alex F. Herrera, Grace Ku, Ji Cheng, Laurie H. Sehn, Matthew J. Matasar, Manali Kamdar, Sarit Assouline, Won Seog Kim, Joseph N. Paulson, Jamie Hirata, Muhit Ozcan, Christopher R. Flowers, Andrew McMillan, Mark Hertzberg, Tae Min Kim, and Elicia Penuel
- Subjects
Adult ,Male ,Cancer Research ,Immunoconjugates ,Antibodies, Monoclonal, Humanized ,Refractory ,Antineoplastic Combined Chemotherapy Protocols ,Biomarkers, Tumor ,Hematologic Malignancy ,Bendamustine Hydrochloride ,Humans ,Medicine ,Refractory Diffuse Large B-Cell Lymphoma ,Progression-free survival ,Survival rate ,Aged ,Aged, 80 and over ,Salvage Therapy ,business.industry ,Antibodies, Monoclonal ,Treatment options ,ORIGINAL REPORTS ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Progression-Free Survival ,Lymphoma ,Polatuzumab vedotin ,Survival Rate ,Oncology ,Monoclonal ,Cancer research ,Female ,Lymphoma, Large B-Cell, Diffuse ,business - Abstract
PURPOSE Patients with transplantation-ineligible relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) fare poorly, with limited treatment options. The antibody-drug conjugate polatuzumab vedotin targets CD79b, a B-cell receptor component. METHODS Safety and efficacy of polatuzumab vedotin with bendamustine and obinutuzumab (pola-BG) was evaluated in a single-arm cohort. Polatuzumab vedotin combined with bendamustine and rituximab (pola-BR) was compared with bendamustine and rituximab (BR) in a randomly assigned cohort of patients with transplantation-ineligible R/R DLBCL (primary end point: independent review committee [IRC] assessed complete response [CR] rate at the end of treatment). Duration of response, progression-free survival (PFS), and overall survival (OS) were analyzed using Kaplan–Meier and Cox regression methods. RESULTS Pola-BG and pola-BR had a tolerable safety profile. The phase Ib/II pola-BG cohort (n = 27) had a CR rate of 29.6% and a median OS of 10.8 months (median follow-up, 27.0 months). In the randomly assigned cohort (n = 80; 40 per arm), pola-BR patients had a significantly higher IRC-assessed CR rate (40.0% v 17.5%; P = .026) and longer IRC-assessed PFS (median, 9.5 v 3.7 months; hazard ratio [HR], 0.36, 95% CI, 0.21 to 0.63; P < .001) and OS (median, 12.4 v 4.7 months; HR, 0.42; 95% CI, 0.24 to 0.75; P = .002; median follow-up, 22.3 months). Pola-BR patients had higher rates of grade 3-4 neutropenia (46.2% v 33.3%), anemia (28.2% v 17.9%), and thrombocytopenia (41% v 23.1%), but similar grade 3-4 infections (23.1% v 20.5%), versus the BR group. Peripheral neuropathy associated with polatuzumab vedotin (43.6% of patients) was grade 1-2 and resolved in most patients. CONCLUSION Polatuzumab vedotin combined with BR resulted in a significantly higher CR rate and reduced the risk of death by 58% compared with BR in patients with transplantation-ineligible R/R DLBCL.
- Published
- 2020
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