Publications by authors named "Steven M Horwitz"

125 Publications

Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19.

JAMA 2021 Feb 24. Epub 2021 Feb 24.

Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts.

Importance: Refinement of criteria for multisystem inflammatory syndrome in children (MIS-C) may inform efforts to improve health outcomes.

Objective: To compare clinical characteristics and outcomes of children and adolescents with MIS-C vs those with severe coronavirus disease 2019 (COVID-19).

Setting, Design, And Participants: Case series of 1116 patients aged younger than 21 years hospitalized between March 15 and October 31, 2020, at 66 US hospitals in 31 states. Final date of follow-up was January 5, 2021. Patients with MIS-C had fever, inflammation, multisystem involvement, and positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase-polymerase chain reaction (RT-PCR) or antibody test results or recent exposure with no alternate diagnosis. Patients with COVID-19 had positive RT-PCR test results and severe organ system involvement.

Exposure: SARS-CoV-2.

Main Outcomes And Measures: Presenting symptoms, organ system complications, laboratory biomarkers, interventions, and clinical outcomes. Multivariable regression was used to compute adjusted risk ratios (aRRs) of factors associated with MIS-C vs COVID-19.

Results: Of 1116 patients (median age, 9.7 years; 45% female), 539 (48%) were diagnosed with MIS-C and 577 (52%) with COVID-19. Compared with patients with COVID-19, patients with MIS-C were more likely to be 6 to 12 years old (40.8% vs 19.4%; absolute risk difference [RD], 21.4% [95% CI, 16.1%-26.7%]; aRR, 1.51 [95% CI, 1.33-1.72] vs 0-5 years) and non-Hispanic Black (32.3% vs 21.5%; RD, 10.8% [95% CI, 5.6%-16.0%]; aRR, 1.43 [95% CI, 1.17-1.76] vs White). Compared with patients with COVID-19, patients with MIS-C were more likely to have cardiorespiratory involvement (56.0% vs 8.8%; RD, 47.2% [95% CI, 42.4%-52.0%]; aRR, 2.99 [95% CI, 2.55-3.50] vs respiratory involvement), cardiovascular without respiratory involvement (10.6% vs 2.9%; RD, 7.7% [95% CI, 4.7%-10.6%]; aRR, 2.49 [95% CI, 2.05-3.02] vs respiratory involvement), and mucocutaneous without cardiorespiratory involvement (7.1% vs 2.3%; RD, 4.8% [95% CI, 2.3%-7.3%]; aRR, 2.29 [95% CI, 1.84-2.85] vs respiratory involvement). Patients with MIS-C had higher neutrophil to lymphocyte ratio (median, 6.4 vs 2.7, P < .001), higher C-reactive protein level (median, 152 mg/L vs 33 mg/L; P < .001), and lower platelet count (<150 ×103 cells/μL [212/523 {41%} vs 84/486 {17%}, P < .001]). A total of 398 patients (73.8%) with MIS-C and 253 (43.8%) with COVID-19 were admitted to the intensive care unit, and 10 (1.9%) with MIS-C and 8 (1.4%) with COVID-19 died during hospitalization. Among patients with MIS-C with reduced left ventricular systolic function (172/503, 34.2%) and coronary artery aneurysm (57/424, 13.4%), an estimated 91.0% (95% CI, 86.0%-94.7%) and 79.1% (95% CI, 67.1%-89.1%), respectively, normalized within 30 days.

Conclusions And Relevance: This case series of patients with MIS-C and with COVID-19 identified patterns of clinical presentation and organ system involvement. These patterns may help differentiate between MIS-C and COVID-19.
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http://dx.doi.org/10.1001/jama.2021.2091DOI Listing
February 2021

ALK-negative anaplastic large cell lymphoma: features and outcomes of 235 patients from the International T-Cell Project.

Blood Adv 2021 Feb;5(3):640-648

CHIMOMO Department and.

Anaplastic lymphoma kinase-negative anaplastic large cell lymphoma (ALK- ALCL) is an aggressive neoplasm of T-cell/null-cell lineage. The T-Cell Project is a global prospective cohort study that consecutively enrolled patients newly diagnosed with peripheral T-cell lymphoma, registered through a centralized computer database between September 2006 and February 2018. Of 1553 validated cases from 74 sites in 13 countries worldwide, 235 were reported as ALK- ALCL. The median age at diagnosis was 54 years (range, 18-89 years), with a male predominance (62%). Stage III to IV disease was identified in 71% of patients, bulky disease and bone marrow involvement were uncommon, and 66% of patients presented with a low (0-1) International Prognostic Index score. Of all treated patients, 85% received multiagent initial chemotherapy, and 8% were consolidated with autologous hematopoietic cell transplantation. The initial overall and complete response rates were 77% and 63%, respectively. After a median follow-up of 52 months (95% confidence interval [CI], 41-63), the median progression-free survival (PFS) and overall survival (OS) were 41 months (95% CI, 17-62) and 55 months (95% CI, 36-75), respectively. The 3- and 5-year PFS rates were 52% and 43%, and the 3- and 5-year OS rates were 60% and 49%. Treatments containing both anthracycline and etoposide were associated with superior OS (P = .05) but not PFS (P = .18). In this large prospective cohort study, outcomes comparable to those previously reported in the retrospective International Peripheral T-Cell Lymphoma Project were observed. The study underscores the need for introducing novel platforms for ALK- ALCL and establishes a benchmark for future clinical trials. This trial was registered at www.clinicaltrials.gov as #NCT01142674.
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http://dx.doi.org/10.1182/bloodadvances.2020001581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876884PMC
February 2021

Active surveillance of primary extranodal marginal zone lymphoma of bronchus-associated lymphoid tissue.

Blood Adv 2021 Jan;5(2):345-351

Memorial Sloan Kettering Cancer Center, New York, NY.

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.
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http://dx.doi.org/10.1182/bloodadvances.2020003213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839366PMC
January 2021

Phase I Study of the CD47 Blocker TTI-621 in Patients with Relapsed or Refractory Hematologic Malignancies.

Clin Cancer Res 2021 Jan 15. Epub 2021 Jan 15.

University of Virginia Cancer Center, Charlottesville, Virginia.

Purpose: TTI-621 (SIRPα-IgG1 Fc) is a novel checkpoint inhibitor that activates antitumor activity by blocking the CD47 "don't eat me" signal. This first-in-human phase I study (NCT02663518) evaluated the safety and activity of TTI-621 in relapsed/refractory (R/R) hematologic malignancies.

Patients And Methods: Patients with R/R lymphoma received escalating weekly intravenous TTI-621 to determine the maximum tolerated dose (MTD). During expansion, patients with various malignancies received weekly single-agent TTI-621 at the MTD; TTI-621 was combined with rituximab in patients with B-cell non-Hodgkin lymphoma (B-NHL) or with nivolumab in patients with Hodgkin lymphoma. The primary endpoint was the incidence/severity of adverse events (AEs). Secondary endpoint included overall response rate (ORR).

Results: Overall, 164 patients received TTI-621: 18 in escalation and 146 in expansion (rituximab combination, = 35 and nivolumab combination, = 4). On the basis of transient grade 4 thrombocytopenia, the MTD was determined as 0.2 mg/kg; 0.1 mg/kg was evaluated in combination cohorts. AEs included infusion-related reactions, thrombocytopenia, chills, and fatigue. Thrombocytopenia (20%, grade ≥3) was reversible between doses and not associated with bleeding. Transient thrombocytopenia that determined the initial MTD may not have been dose limiting. The ORR for all patients was 13%. The ORR was 29% (2/7) for diffuse large B-cell lymphoma (DLBCL) and 25% (8/32) for T-cell NHL (T-NHL) with TTI-621 monotherapy and was 21% (5/24) for DLBCL with TTI-621 plus rituximab. Further dose optimization is ongoing.

Conclusions: TTI-621 was well-tolerated and demonstrated activity as monotherapy in patients with R/R B-NHL and T-NHL and combined with rituximab in patients with R/R B-NHL.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-3706DOI Listing
January 2021

NCCN Guidelines Insights: T-Cell Lymphomas, Version 1.2021.

J Natl Compr Canc Netw 2020 11 2;18(11):1460-1467. Epub 2020 Nov 2.

28National Comprehensive Cancer Network.

Hepatosplenic T-cell lymphoma (HSTCL) is a rare subtype of T-cell lymphoma associated with an aggressive clinical course and a worse prognosis. HSTCL develops in the setting of chronic immune suppression or immune dysregulation in up to 20% of cases and is most often characterized by spleen, liver, and bone marrow involvement. Diagnosis and management of HSTCL pose significant challenges given the rarity of the disease along with the absence of lymphadenopathy and poor outcome with conventional chemotherapy regimens. These Guidelines Insights focus on the diagnosis and treatment of HSTCL as outlined in the NCCN Guidelines for T-Cell Lymphomas.
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http://dx.doi.org/10.6004/jnccn.2020.0053DOI Listing
November 2020

Clinical characteristics and outcomes of extranodal stage I diffuse large B-cell lymphoma in the rituximab era.

Blood 2021 Jan;137(1):39-48

Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.

This retrospective study aimed to better define the characteristics and outcomes of extranodal stage I diffuse large B-cell lymphoma (DLBCL) in the rituximab era. Patients diagnosed with stage I DLBCL from 2001 to 2015 treated with rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) or R-CHOP-like regimens with or without radiation (RT) were included. We identified 1955 patients with newly diagnosed DLBCL, of whom 341 had stage I and were eligible for this analysis. Extranodal presentation was observed in 224 (66%) patients, whereas 117 (34%) had nodal involvement. The most common extranodal sites were as follows: bone, 21%; stomach, 19%; testis, 9%; intestine, 8%; breast, 8%. Overall, 69% extranodal patients and 68% nodal patients received RT. Median follow-up was 5.5 years (interquartile range, 4.3-8.2). Ten-year overall survival (OS) and disease-free survival were 77% (95% confidence interval [CI], 67%-83%) and 77% (95% CI, 68%-85%). In the multivariable analyses, extranodal involvement was associated with worse OS (hazard ratio [HR], 3.44; 95% CI, 1.05-11.30) and progression-free survival (PFS; HR, 3.25; 95% CI, 1.08-9.72) compared with nodal involvement. Consolidation RT was associated with better OS (HR, 0.26; 95% CI, 0.12-0.49) and PFS (HR, 0.35; 95% CI, 0.18-0.69) in the extranodal population; however, the benefit was no longer observed in patients that were positron emission tomography (PET) negative at the end of immunochemotherapy. Relapses occurred usually late (median, 37 months), and the most common sites were the lymph nodes (31%) and the central nervous system (27%). Extranodal stage I DLBCL had a worse outcome than nodal stage 1 DLBCL. End of immunochemotherapy PET results may help select extranodal patients for consolidation RT.
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http://dx.doi.org/10.1182/blood.2020005112DOI Listing
January 2021

Follicular lymphoma in the modern era: survival, treatment outcomes, and identification of high-risk subgroups.

Blood Cancer J 2020 07 17;10(7):74. Epub 2020 Jul 17.

Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Patients with follicular lymphoma (FL) frequently require multiple treatments during their disease course; however, survival based on lines of treatment remains poorly described in the post-rituximab era. Also, the Follicular Lymphoma International Prognostic Index (FLIPI) score was developed to predict survival at diagnosis, yet it remains unknown whether increase in FLIPI score following an initial observation period is associated with less-favorable outcomes. To address these knowledge gaps, we retrospectively studied 1088 patients with FL grade 1-3A managed between 1998 and 2009 at our institution. Median overall survival (OS) and progression-free survival (PFS) after first-line treatment were not reached and 4.73 years, respectively. Following successive lines of treatment, years of median OS and PFS were, respectively: after second-line, 11.7 and 1.5; third-line, 8.8 and 1.1; fourth-line, 5.3 and 0.9; fifth-line, 3.1 and 0.6; sixth-line, 1.9 and 0.5. In initially observed, subsequently treated patients, FLIPI score increase after observation was associated with inferior survival following first-line treatment. The reduced survival we observed after second-line and later therapy supports the development of new treatments for relapsed patients and benchmarks historical targets for clinical endpoints. This study also highlights the utility of changes in FLIPI score at diagnosis and after observation in identifying patients likely to have worse outcomes.
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http://dx.doi.org/10.1038/s41408-020-00340-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366724PMC
July 2020

Multisystem Inflammatory Syndrome in U.S. Children and Adolescents.

N Engl J Med 2020 07 29;383(4):334-346. Epub 2020 Jun 29.

From the COVID-19 Response, Centers for Disease Control and Prevention (L.R.F., E.B.R., J.P.C., M.W.T., M.M.P.), and the Division of Critical Care Medicine, Department of Pediatrics (K.M.T.), the Department of Pediatrics, Division of Infectious Diseases (P.J.), and the Department of Pediatrics, Division of Cardiology (M.E.O.), Emory University School of Medicine, Atlanta; Public Health Service Commissioned Corps, Rockville (L.R.F., E.B.R., M.M.P.), and the Department of Anesthesiology and Critical Care Medicine, Division of Pediatric Anesthesiology and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore (B.J.R.) - both in Maryland; the Department of Pediatrics, Division of Pediatric Critical Care, Bristol-Myers Squibb Children's Hospital, Robert Wood Johnson Medical School, Rutgers University (S.M. Horwitz), the Department of Pediatrics, Division of Population Health, Quality, and Implementation Sciences (PopQuIS), Rutgers Robert Wood Johnson Medical School (L.C.K.), New Brunswick, the Department of Pediatrics, Division of Pediatric Cardiology, Children's Hospital of New Jersey, Newark Beth Israel, Newark (R.F.W.), the Division of Hospital Medicine, Department of Pediatrics, Hackensack University Medical Center, Hackensack (K.N.C.), and the Division of Pediatric Critical Care, Department of Pediatrics, Saint Barnabas Medical Center, Livingston (S.J.G.) - all in New Jersey; the Department of Anesthesiology, Critical Care and Pain Medicine (M.M.N., A.G.R.), the Division of Immunology (M.B.F.S.), and the Department of Cardiology (J.W.N.), Boston Children's Hospital, and the Departments of Pediatrics (M.B.F.S., J.W.N., A.G.R.) and Anaesthesia (A.G.R.), Harvard Medical School, Boston, and the Department of Pediatrics, Pediatric Critical Care, Baystate Medical Center, Springfield (K.L.M.) - both in Massachusetts; the Department of Pediatrics, Division of Pediatric Critical Care Medicine, Central Michigan University, Detroit (S.M. Heidemann, A.A.M.); the Pediatric Critical Care Division, Maria Fareri Children's Hospital at Westchester Medical Center and New York Medical College, Valhalla (A.R.S., S.L.), Pediatric Critical Care Medicine, Department of Pediatrics, Icahn School of Medicine at the Mount Sinai Kravis Children's Hospital (S.P.Z., J.G.), the Division of Pediatric Infectious Diseases, Departments of Pediatrics and Microbiology, New York University Grossman School of Medicine (A.J.R.), Pediatric Critical Care, New York City Health and Hospitals, Kings County Hospital (M.A.K., H.A.), the Division of Pediatric Critical Care, Department of Pediatrics, SUNY Downstate Health Sciences University (S.D.), and the Department of Pediatrics, Division of Pediatric Critical Care, Maimonides Children's Hospital (A.D.), New York - all in New York; the Division of Critical Care, Department of Anesthesiology and Critical Care, University of Pennsylvania Perelman School of Medicine, Philadelphia (J.C.F.); the Department of Pediatrics, Division of Critical Care, Yale University School of Medicine, New Haven (J.S.G., A.G.), and the Division of Critical Care, Connecticut Children's, Hartford (R.M.P., C.L.C.) - both in Connecticut; the Department of Pediatrics, Section of Critical Care Medicine, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora (A.B.M.); the Division of Pediatric Critical Care Medicine, Department of Pediatrics, Advocate Children's Hospital, Chicago (V.H., S.R.); the Department of Pediatrics, Division of Pediatric Rheumatology, MetroHealth Medical Center, Case Western Reserve University (H.B.), and the Division of Pediatric Hospital Medicine, Rainbow Babies and Children's Hospital (A.L.), Cleveland; the Department of Pediatrics, Division of Cardiology, Louisiana State University Health Sciences Center and Children's Hospital of New Orleans, New Orleans (T.T.B.); the Department of Pediatrics, Division of Pediatric Critical Care Medicine, University of Washington, Seattle (L.S.S.); the Pediatric Critical Care Division, Department of Pediatrics, University of Texas Health Science Center at Houston, Houston (A.C.M.); the Department of Pediatrics, Department of Microbiology, Division of Infectious Diseases, University of Mississippi Medical Center, Jackson (C.V.H.); and the Division of Pediatric Infectious Diseases, Department of Pediatrics, Vanderbilt University Medical Center, Nashville (N.B.H.).

Background: Understanding the epidemiology and clinical course of multisystem inflammatory syndrome in children (MIS-C) and its temporal association with coronavirus disease 2019 (Covid-19) is important, given the clinical and public health implications of the syndrome.

Methods: We conducted targeted surveillance for MIS-C from March 15 to May 20, 2020, in pediatric health centers across the United States. The case definition included six criteria: serious illness leading to hospitalization, an age of less than 21 years, fever that lasted for at least 24 hours, laboratory evidence of inflammation, multisystem organ involvement, and evidence of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on reverse-transcriptase polymerase chain reaction (RT-PCR), antibody testing, or exposure to persons with Covid-19 in the past month. Clinicians abstracted the data onto standardized forms.

Results: We report on 186 patients with MIS-C in 26 states. The median age was 8.3 years, 115 patients (62%) were male, 135 (73%) had previously been healthy, 131 (70%) were positive for SARS-CoV-2 by RT-PCR or antibody testing, and 164 (88%) were hospitalized after April 16, 2020. Organ-system involvement included the gastrointestinal system in 171 patients (92%), cardiovascular in 149 (80%), hematologic in 142 (76%), mucocutaneous in 137 (74%), and respiratory in 131 (70%). The median duration of hospitalization was 7 days (interquartile range, 4 to 10); 148 patients (80%) received intensive care, 37 (20%) received mechanical ventilation, 90 (48%) received vasoactive support, and 4 (2%) died. Coronary-artery aneurysms (z scores ≥2.5) were documented in 15 patients (8%), and Kawasaki's disease-like features were documented in 74 (40%). Most patients (171 [92%]) had elevations in at least four biomarkers indicating inflammation. The use of immunomodulating therapies was common: intravenous immune globulin was used in 144 (77%), glucocorticoids in 91 (49%), and interleukin-6 or 1RA inhibitors in 38 (20%).

Conclusions: Multisystem inflammatory syndrome in children associated with SARS-CoV-2 led to serious and life-threatening illness in previously healthy children and adolescents. (Funded by the Centers for Disease Control and Prevention.).
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http://dx.doi.org/10.1056/NEJMoa2021680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346765PMC
July 2020

Outcomes of Patients with Transformed Mycosis Fungoides: Analysis from a Prospective Multicenter US Cohort Study.

Clin Lymphoma Myeloma Leuk 2020 Nov 11;20(11):744-748. Epub 2020 May 11.

Yale University, New Haven, CT. Electronic address:

Introduction: We examined patient characteristics, treatments, and outcomes of patients with transformed mycosis fungoides (tMF) from COMPLETE: a large, multicenter, prospective cohort study of peripheral T-cell lymphoma patients in the United States.

Methods: Patients with tMF were enrolled in COMPLETE at the time of transformation. For this analysis, we identified patients with tMF with completed baseline, treatment, and follow-up records. Median survival was assessed using Kaplan-Meier methodology.

Results: Of the 499 patients enrolled in COMPLETE, 17 had tMF. Median age was 61; 53% were male, 9 had elevated lactate dehydrogenase, and 9 had lymph node involvement. Approximately one-quarter of the patients were African American and 47% had CD30+ disease. Median time to transformation was 53 months. All patients received systemic therapy, with 19% receiving concomitant radiotherapy. Most patients (87%) received single agents, including liposomal doxorubicin, pralatrexate, and gemcitabine. Eight patients (50%) had reported responses to therapy. Median survival was 18 months. One- and 2-year survival rates were 56% and 44%, respectively.

Conclusions: tMF often expresses CD30 and presents with lymph node involvement. Responses have been seen with single agents, but survival remains poor. Novel treatment approaches are urgently needed to improve outcomes.
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http://dx.doi.org/10.1016/j.clml.2020.05.001DOI Listing
November 2020

Patient-reported quality of life in patients with relapsed/refractory cutaneous T-cell lymphoma: Results from the randomised phase III ALCANZA study.

Eur J Cancer 2020 07 2;133:120-130. Epub 2020 Jun 2.

University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Box 1452, Houston, TX, USA. Electronic address:

Background: Brentuximab vedotin was approved for adult patients with CD30-expressing cutaneous T-cell lymphoma treated with prior systemic therapy based on improved response rates and progression-free survival with brentuximab vedotin (1.8 mg/kg once every 3 weeks; ≤16 cycles) versus physician's choice (methotrexate/bexarotene; ≤48 weeks) in the phase III ALCANZA study. Quality of life (QoL) in ALCANZA patients was also examined.

Methods: QoL measures in ALCANZA were based on the Skindex-29, Functional Assessment of Cancer Therapy-General (FACT-G) and European QoL 5-dimension (EQ-5D) questionnaires.

Results: Mean maximum reduction from the baseline Skindex-29 symptom domain score (key secondary end-point) was greater with brentuximab vedotin than physician's choice (-27.96 versus -8.62); the difference, -18.9 (95% confidence interval -26.6, -11.2; adjusted p < 0.001), exceeded the study-defined minimally important difference (9.0-12.3). Mean changes from baseline to end-of-treatment visit total FACT-G scores were similar with brentuximab vedotin and physician's choice (0.15 versus -2.29). EQ-5D changes were also comparable between arms. Among brentuximab vedotin-treated patients with peripheral neuropathy (PN), mean maximum reduction in Skindex-29 symptom domain was -35.54 versus -11.11 in patients without PN. PN had no meaningful effect on FACT-G and EQ-5D QoL scores.

Conclusions: In summary, brentuximab vedotin produced superior reductions in symptom burden compared with physician's choice, without adversely impacting QoL. QoL was unaffected by the presence of PN in brentuximab vedotin-treated patients.

Clinical Trial Registration: NCT01578499.
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http://dx.doi.org/10.1016/j.ejca.2020.04.010DOI Listing
July 2020

Clonal hematopoiesis in angioimmunoblastic T-cell lymphoma with divergent evolution to myeloid neoplasms.

Blood Adv 2020 05;4(10):2261-2271

Hematopathology Service, Department of Pathology.

TET2 and DNMT3A mutations are frequently identified in T-cell lymphomas of T follicular helper cell origin (TCL-TFH), clonal hematopoiesis (CH), and myeloid neoplasms (MNs). The relationships among these 3 entities, however, are not well understood. We performed comprehensive genomic studies on paired bone marrow and tissue samples as well as on flow cytometry-sorted bone marrow and peripheral blood subpopulations from a cohort of 22 patients with TCL-TFH to identify shared CH-type mutations in various hematopoietic cell compartments. Identical mutations were detected in the neoplastic T-cell and myeloid compartments of 15 out of 22 patients (68%), including TET2 (14/15) and DNMT3A (10/15). Four patients developed MNs, all of which shared CH-type mutations with their TCL-TFH; additional unique genetic alterations were also detected in each patient's TCL-TFH and MN. These data demonstrate that CH is prevalent in patients with TCL-TFH and that divergent evolution of a CH clone may give rise to both TCL-TFH and MNs.
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http://dx.doi.org/10.1182/bloodadvances.2020001636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7252546PMC
May 2020

NCCN Guidelines Insights: Primary Cutaneous Lymphomas, Version 2.2020.

J Natl Compr Canc Netw 2020 05;18(5):522-536

Stanford Cancer Institute.

Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma (CTCL), and Sézary syndrome (SS) is a rare erythrodermic and leukemic subtype of CTCL characterized by significant blood involvement. Although early-stage disease can be effectively treated predominantly with skin-directed therapies, systemic therapy is often necessary for the treatment of advanced-stage disease. Systemic therapy options have evolved in recent years with the approval of novel agents such as romidepsin, brentuximab vedotin, and mogamulizumab. These NCCN Guidelines Insights discuss the diagnosis and management of MF and SS (with a focus on systemic therapy).
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http://dx.doi.org/10.6004/jnccn.2020.0022DOI Listing
May 2020

Bright PD-1 expression by flow cytometry is a powerful tool for diagnosis and monitoring of angioimmunoblastic T-cell lymphoma.

Blood Cancer J 2020 03 6;10(3):32. Epub 2020 Mar 6.

Hematopathology Service, Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

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http://dx.doi.org/10.1038/s41408-020-0301-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060322PMC
March 2020

Survival outcomes of patients with extranodal natural-killer T-cell lymphoma: a prospective cohort study from the international T-cell Project.

Lancet Haematol 2020 Apr 24;7(4):e284-e294. Epub 2020 Feb 24.

Division of Hematology-Oncology, Samsung Medical Center, Seoul, South Korea. Electronic address:

Background: Extranodal natural killer (NK) T-cell lymphoma (ENKTL) is a unique clinicopathological entity, typically associated with poor survival outcomes. Most published data have come from east Asian study groups, with little information available from international cohorts. The effects of treatment advances on routine clinical practice across continental territories has not been clear. We aimed to improve understanding of the clinical characteristics and outcomes of patients with ENKTL.

Methods: We did a substudy of patients with ENKTL from the T-cell Project, a global prospective cohort study. The T-cell Project registered consecutively diagnosed adults (>18 years) with newly diagnosed, untreated mature T-cell or NK lymphomas (WHO 2001 or 2008 classifications) from 74 centres in 13 countries (in Asia, Europe, North America, and South America). In total, 1695 patients with mature T-cell or NK lymphomas were enrolled between Oct 12, 2006 and Feb 28, 2018 in the T-cell Project. The first patient with ENKTL was enrolled on Feb 15, 2007, and the last on May 26, 2017. Data on baseline characteristics, first-line treatment, treatment response, and survival outcomes were recorded in a central database (locked March 30, 2019). The primary outcome was 5-year overall survival. The T-cell Project is registered on ClinicalTrials.gov, NCT01142674.

Findings: 166 patients were diagnosed with ENKTL, comprising 11% of 1553 eligible registered cases and distributed across 40 participating centres in four continents. At a median follow-up of 44 months (IQR 20-61), overall survival at 5 years was 54% (95% CI 44-63) in patients with nasal disease (n=98) and 34% (27-46) in patients with extranasal disease (n=68).

Interpretation: To our knowledge, this study presents the largest international cohort of patients with ENKTL. We describe a clinically significant improvement in the survival of patients with ENKTL treated in routine clinical practice over the past decade, likely to be attributable to the increasing use of treatment protocols specific for ENKTL.

Funding: The Fondazione Cassa di Risparmio di Modena, the Associazione Angela Serra per la Ricerca sul Cancro, the Fondazione Italiana Linfomi, Allos Therapeutics, Spectrum Pharmaceuticals, Associazione Italiana per la Ricerca sul Cancro, and the National Cancer Institute at the National Institutes of Health.
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http://dx.doi.org/10.1016/S2352-3026(19)30283-2DOI Listing
April 2020

Risk of breast implant associated anaplastic large cell lymphoma (BIA-ALCL) in a cohort of 3546 women prospectively followed long term after reconstruction with textured breast implants.

J Plast Reconstr Aesthet Surg 2020 05 20;73(5):841-846. Epub 2020 Jan 20.

Lymphoma Service, Division of Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065, United States.

Background: The risk of BIA-ALCL for patients with textured breast implants has been estimated between 1/2832 and 1/30,000 women. Existing studies estimating the numbers exposed and at risk, may have under reported cases, and/or lacked comprehensive follow-up. Our objective is to determine the risk of BIA-ALCL in a defined cohort of patients reconstructed with macro-textured breast implants and consistently followed long-term.

Methods: A prospective cohort study was conducted in patients who underwent breast reconstruction by a single surgeon at Memorial Sloan Kettering Cancer Center (MSKCC) from December 1992 to December 2017. Major events related to implants were prospectively recorded. We identified cases of BIA-ALCL by cross-checking clinical, pathology and external records data. Patients were followed until lymphoma occurrence or last follow-up. The primary outcomes were incidence rate per person-years and cumulative incidence.

Results: From 1992 to 2017, 3546 patients underwent 6023 breast reconstructions, mainly after breast cancer removal, or contralateral prophylactic mastectomy, using macro-textured surface expanders and implants. All reconstructions were performed by a single surgeon (PGC). Median follow-up was 8.1 years (range, 3 months - 30.9 years). Ten women, 1/354, developed ALCL after a median exposure of 11.5 years (range, 7.4-15.8 years). Overall risk of BIA-ALCL in our cohort is 1/355 women or 0.311 cases per 1000 person-years (95% CI 0.118 to 0.503).

Discussion: This study, the first to evaluate the risk of macro-textured breast implants from a prospective database with long term follow-up, demonstrates that the incidence rate of BIA-ALCL may be higher than previously reported. These results can help inform implant choice for women undergoing breast reconstruction.
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http://dx.doi.org/10.1016/j.bjps.2019.11.064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247945PMC
May 2020

Incidence and outcomes of rare T cell lymphomas from the T Cell Project: hepatosplenic, enteropathy associated and peripheral gamma delta T cell lymphomas.

Am J Hematol 2020 02 25;95(2):151-155. Epub 2019 Nov 25.

CHIMOMO Department University of Modena and Reggio Emilia, Modena, Italy.

The T Cell Project was the largest prospective trial to explore the incidence, treatment patterns, and outcomes for T cell lymphomas. The rare subtypes of T cell lymphomas, including hepatosplenic T cell lymphoma (HSTCL), enteropathy associated T cell lymphoma (EATL), and peripheral gamma delta T cell lymphomas (PGDTCLs) are poorly represented in most studies and there is little data regarding treatment patterns. We report results from 115 patients with hepatosplenic (n = 31), enteropathy associated (n = 65), and PGDTCLs (n = 19). While anthracycline regimens were most commonly used as first line therapy, response rates ranged from 20%-40% and were suboptimal for all groups. Autologous stem cell transplantation was performed as a consolidation in first remission in a small number of patients (33% of HSTCL, 7% of EATL, and 12% of PGDTCL), and four patients with HSTCL underwent allogeneic stem cell transplantation in first remission. The progression free survival at 3 years ranged from 28%-40% for these rare subtypes, and the overall survival at 3 years was most favorable for PGDTCL (70%). These data highlight the need for novel treatment approaches for rare subtypes of T cell lymphomas and for their inclusion in clinical trials.
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http://dx.doi.org/10.1002/ajh.25674DOI Listing
February 2020

TFH lymphomas: the times they aza-changin'?

Blood 2019 10;134(17):1364-1365

Memorial Sloan Kettering Cancer Center.

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http://dx.doi.org/10.1182/blood.2019002806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6839955PMC
October 2019

Incidence of benign and malignant peri-implant fluid collections and masses on magnetic resonance imaging in women with silicone implants.

Cancer Med 2020 05 30;9(10):3261-3267. Epub 2019 Sep 30.

Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.

Background: To assess the incidence of benign and malignant peri-implant fluid collections and/or masses on magnetic resonance imaging (MRI) in women with silicone implants who are being screened for silent implant rupture.

Methods: The institutional review board approved this HIPAA-compliant retrospective study and waived informed consent. Women who underwent silicone implant oncoplastic and/or cosmetic surgery and postoperative implant-protocol MRI from 2000 to 2014 were included. Peri-implant fluid collections and/or masses were measured volumetrically. A benign peri-implant fluid collection and/or mass was pathologically proven or defined as showing 2 years of imaging and/or clinical stability. A malignant peri-implant fluid collection was pathologically proven. Incidence of peri-implant fluid collections and/or masses and positive predictive value (PPV) were calculated on a per-patient level using proportions and exact 95% confidence intervals (CIs). Fisher's exact test was used in the analysis to test statistical significance pre-defined as P-value < 0.05.

Results: A total of 1070 women with silicone implants were included (mean age, 50.7 years; range, 40.4-53.8). Median time between reconstructive surgery and first MRI was 88.9 months (range, 0.8-1363.3). Eighteen women (1.7%) had a peri-implant fluid collection and/or mass: 15/18 (83.3%) had adequate follow-up; and only 1/15 was malignant implant associated anaplastic large cell lymphoma, with a PPV of 6.7% (95% CI: 0.003-0.0005). The median peri-implant fluid collection size was 89 mL (range, 18-450 mL).

Conclusion: Peri-implant fluid collections and/or masses identified at silicone implant protocol breast MR imaging are rarely seen 24 months after reconstructive surgery. Image-guided fine-needle aspiration with flow cytometry may be warranted to evaluate for implant-associated lymphoma.
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http://dx.doi.org/10.1002/cam4.2189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221432PMC
May 2020

Pembrolizumab in Relapsed and Refractory Mycosis Fungoides and Sézary Syndrome: A Multicenter Phase II Study.

J Clin Oncol 2020 01 18;38(1):20-28. Epub 2019 Sep 18.

Stanford University, Stanford, CA.

Purpose: To assess the efficacy of pembrolizumab in patients with advanced relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS).

Patients And Methods: CITN-10 is a single-arm, multicenter phase II trial of 24 patients with advanced MF or SS. Patients were treated with pembrolizumab 2 mg/kg every 3 weeks for up to 24 months. The primary end point was overall response rate by consensus global response criteria.

Results: Patients had advanced-stage disease (23 of 24 with stage IIB to IV MF/SS) and were heavily pretreated with a median of four prior systemic therapies. The overall response rate was 38% with two complete responses and seven partial responses. Of the nine responding patients, six had 90% or more improvement in skin disease by modified Severity Weighted Assessment Tool, and eight had ongoing responses at last follow-up. The median duration of response was not reached, with a median response follow-up time of 58 weeks. Immune-related adverse events led to treatment discontinuation in four patients. A transient worsening of erythroderma and pruritus occurred in 53% of patients with SS. This cutaneous flare reaction did not result in treatment discontinuation for any patient. The flare reaction correlated with high PD-1 expression on Sézary cells but did not associate with subsequent clinical responses or lack of response. Treatment responses did not correlate with expression of PD-L1, total mutation burden, or an interferon-γ gene expression signature.

Conclusion: Pembrolizumab demonstrated significant antitumor activity with durable responses and a favorable safety profile in patients with advanced MF/SS.
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http://dx.doi.org/10.1200/JCO.19.01056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943974PMC
January 2020

Outcomes and prognostic factors in African American and black patients with mycosis fungoides/Sézary syndrome: Retrospective analysis of 157 patients from a referral cancer center.

J Am Acad Dermatol 2020 Aug 6;83(2):430-439. Epub 2019 Sep 6.

Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York.

Background: The prevalence of mycosis fungoides/Sézary syndrome (MF/SS) is higher in the black population than in the white population in the United States and worse outcomes have been observed in black patients.

Objective: To describe the outcomes and to identify prognostic factors in African American and black patients with MF/SS.

Methods: Clinical features and follow-up data were analyzed in 157 self-identified African American or black patients seen during 1994-2018.

Results: We included 122 patients with early stage MF and 35 patients with advanced-stage disease (median follow-up of 25 months). Overall, >80% of the patients who died from disease or progressed had erythema or hyperpigmentation without hypopigmentation. Patients with hypopigmentation, either as the sole manifestation or in combination with other lesions, had better overall survival (P = .002) and progression-free survival (P = .014). Clinical stage, TNMB classification, plaque disease, and elevated serum lactate dehydrogenase were also significantly associated with outcomes. Demographic and socioeconomic parameters were not associated with prognosis.

Limitations: A retrospective study at a single cancer center.

Conclusion: MF/SS manifestations and outcomes in African American and black patients are heterogeneous. Demographic and socioeconomic factors do not seem to have a prognostic role, while clinical characteristics might help in the stratification of risk of progression and shorter survival, allowing for individually tailored therapeutic interventions.
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http://dx.doi.org/10.1016/j.jaad.2019.08.073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058509PMC
August 2020

C-C chemokine receptor 4 expression in CD8+ cutaneous T-cell lymphomas and lymphoproliferative disorders, and its implications for diagnosis and treatment.

Histopathology 2020 Jan 13;76(2):222-232. Epub 2019 Nov 13.

Department of Pathology, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA.

Aims: Patients with aggressive CD8+ cutaneous T-cell lymphomas (CTCLs) progress rapidly and respond poorly to therapy. Confounding treatment planning, there is clinicopathological overlap between aggressive CD8+ CTCLs and other lymphoproliferative disorders (LPDs). Hence, improved diagnostic methods and therapeutic options are needed. The aim of this study was to examine C-C chemokine receptor 4 (CCR4) expression as a diagnostic and therapeutic biomarker in CD8+ CTCLs/LPDs.

Methods And Results: Forty-nine cases (41 patients) with CD8+ CTCLs/LPDs were examined, including CD8+ mycosis fungoides (MF) (n = 14), aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma (AETCL) (n = 8), subcutaneous panniculitis-like T-cell lymphoma (SPTCL) (n = 7), CD30+ LPDs (n = 6), primary cutaneous γδ T-cell lymphoma (GDTCL) (n = 6), and others (n = 8). Immunohistochemical tissue staining was performed with a CCR4 monoclonal antibody on formalin-fixed paraffin-embedded tissue sections. CCR4 immunostaining was graded as percentage infiltrate, i.e. high (>25%) and low (≤25%), and the results were correlated with clinicopathological diagnoses. CCR4 expression was seen in 69% of the studied cases. Any CCR4 positivity was seen in all CD8+ MF cases, in 83% of CD30+ LPD cases, in 75% of AETCL cases, in 33% of GDTCL cases, and in none of the SPTCL cases. High CCR4 expression was seen in 79% of CD8+ MF cases versus 33% of CD30+ LPD cases, in 17% of GDTCL cases, and in 12.5% of AETCL cases. Patients with more advanced MF stage had higher CCR4 expression.

Conclusions: CCR4 immunohistochemistry may be an adjunct in distinguishing advanced CD8+ MF from other CD8+ CTCLs/LPDs. Although CCR4 expression may justify therapeutic targeting of this receptor in CD8+ MF, the role of such therapies in other CD8+ CTCLs/LPDs is not yet clear.
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http://dx.doi.org/10.1111/his.13960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577561PMC
January 2020

Outcomes for Relapsed and Refractory Peripheral T-Cell Lymphoma Patients after Front-Line Therapy from the COMPLETE Registry.

Acta Haematol 2020 17;143(1):40-50. Epub 2019 Jul 17.

Yale University, New Haven, Connecticut, USA,

Background: Outcomes for patients with peripheral T-cell lymphoma (PTCL) who fail to achieve complete response (CR) or relapse after front-line therapy are poor with lack of prospective outcomes data.

Objectives: COMPLETE is a prospective registry of 499 patients enrolled at academic and community sites in the United States detailing patient demographics, treatment and outcomes for patients with aggressive T cell lymphomas. We report results for patients with primary refractory and relapsed disease.

Methods: Primary refractory disease was defined as an evaluable best response to initial treatment (induction ± maintenance or consolidation/transplant) other than CR, and included a partial response, progressive disease, or no response/stable disease. Relapsed disease was defined as an evaluable best response to initial treatment of CR, followed by disease progression at a later date, irrespective of time to progression. Patients were included in the analysis if initial treatment began within 30 days of enrollment and treatment duration was ≥4 days.

Results: Of 420 evaluable patients, 97 met the definition for primary refractory and 58 with relapsed disease. In the second-line setting, relapsed patients received single-agent therapies more often than refractory patients (52 vs. 28%; p = 0.01) and were more likely to receive single-agent regimens (74 vs. 53%; p = 0.03). The objective response rate to second-line therapy was higher in relapsed patients (61 vs. 40%; p = 0.04) as was the proportion achieving a CR (41 vs. 14%; p = 0.002). Further, relapsed patients had longer overall survival (OS) compared to refractory patients, with a median OS of 29.1 versus 12.3 months.

Conclusions: Despite the availability of newer active single agents, refractory patients were less likely to receive these therapies and continue to have inferior outcomes compared to those with relapsed disease. PTCL in the real world remains an unmet medical need, and improvements in front-line therapies are needed.
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http://dx.doi.org/10.1159/000500666DOI Listing
April 2020

Multicenter analysis of outcomes in blastic plasmacytoid dendritic cell neoplasm offers a pretargeted therapy benchmark.

Blood 2019 08 26;134(8):678-687. Epub 2019 Jun 26.

Dana-Farber Cancer Institute, and.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an uncommon hematologic malignancy with poor outcomes. Existing data on the clinical behavior of BPDCN are limited because reported outcomes are from small retrospective series, and standardized treatment guidelines are lacking. The interleukin-3 cytotoxin conjugate tagraxofusp was recently tested in phase 1/2 trials that led to US Food and Drug Administration approval, the first ever for BPDCN. However, because there was no matched internal comparator in this or any clinical study to date, results of BPDCN trials testing new drugs are difficult to compare with alternative therapies. We therefore sought to define the clinical characteristics and outcomes of a group of patients with BPDCN treated at 3 US cancer centers in the modern era but before tagraxofusp was available. In 59 studied patients with BPDCN, the median overall survival from diagnosis was 24 months, and outcomes were similar in patients with "skin only" or with systemic disease at presentation. Intensive first-line therapy and "lymphoid-type" chemotherapy regimens were associated with better outcomes. Only 55% of patients received intensive chemotherapy, and 42% of patients underwent stem cell transplantation. Clinical characteristics at diagnosis associated with poorer outcomes included age >60 years, abnormal karyotype, and terminal deoxynucleotidyltransferase (TdT) negativity in the BPDCN cells. We also identified disease responses to pralatrexate and enasidenib in some patients. This study highlights poor outcomes for patients with BPDCN in the modern era and the need for new treatments. Outcomes from ongoing clinical trials for BPDCN can be evaluated relative to this contemporary cohort.
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http://dx.doi.org/10.1182/blood.2019001144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6706810PMC
August 2019

Patterns of survival in patients with recurrent mantle cell lymphoma in the modern era: progressive shortening in response duration and survival after each relapse.

Blood Cancer J 2019 05 20;9(6):50. Epub 2019 May 20.

Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

As the survival of patients with mantle cell lymphoma (MCL) continues to improve, patients are increasingly being treated with multiple regimens. However, outcome after each line remains poorly characterized in the modern era. To address this knowledge gap, we retrospectively studied 404 consecutive MCL patients who were managed between 2000 and 2014 at Memorial Sloan Kettering Cancer Center. Histologic diagnosis was centrally confirmed, and patients were followed longitudinally from diagnosis throughout their disease course. Progression-free survival (PFS) and overall survival (OS) were determined by Kaplan-Meier method. The median OS and PFS after first-line treatment were 9.7 and 4.0 years, respectively. After second-line therapy, the median OS and PFS were 41.1 and 14.0 months, third line were 25.2 and 6.5 months, and fourth line were 14.4 and 5.0 months. In patients less than 65 years, stem cell transplant (SCT)-based frontline regimens were associated with improved PFS compared with non-SCT regimens (median PFS: 86.2 versus 40.0 months; P < 0.01), with a trend toward longer OS (median OS: 165.0 versus 120.0 months; P = 0.06). Early treatment failure after first-line regimens was associated with worse OS (5.9 versus 2.5 years; P < 0.01). Our study should facilitate establishing proper endpoints for future clinical trials using novel treatment approaches.
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http://dx.doi.org/10.1038/s41408-019-0209-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6527702PMC
May 2019

Targeting CD47 in Sézary syndrome with SIRPαFc.

Blood Adv 2019 04;3(7):1145-1153

Department of Dermatology, University of Pittsburgh, Pittsburgh, PA.

Sézary syndrome (SS), the leukemic variant of cutaneous T-cell lymphoma, has limited treatment options and rare occurrences of long-term remission, thus warranting research into new treatment approaches. CD47 has emerged as a promising target for multiple tumor types, but its role in SS remains unknown. Here, we show that CD47 is highly expressed on Sézary cells in the peripheral blood and skin, and the high level of CD47 expression correlates with worse overall survival (OS) in patients with SS. We also demonstrate that CD47 expression on Sézary cells is under the influence of interleukin 4 (IL-4), IL-7, and IL-13. Signal regulatory protein αFc (SIRPαFc; TTI-621), a novel CD47 decoy receptor, triggers macrophage-mediated phagocytosis of Sézary cells and, when administered in clinical trial settings, results in significant tumor load reduction. We conclude that inhibition of the CD47-SIRPα signaling pathway has therapeutic benefit for patients with SS. This trial was registered at www.clinicaltrials.gov as #NCT02663518.
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http://dx.doi.org/10.1182/bloodadvances.2018030577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457236PMC
April 2019

Single agents vs combination chemotherapy in relapsed and refractory peripheral T-cell lymphoma: Results from the comprehensive oncology measures for peripheral T-cell lymphoma treatment (COMPLETE) registry.

Am J Hematol 2019 06 9;94(6):641-649. Epub 2019 Apr 9.

Division of Hematologic Malignancies and and Bone Marrow Transplantation, Beth Israel Deaconess Medical Center, Boston, Massachusetts.

Single agents have demonstrated activity in relapsed and refractory (R/R) peripheral T-cell lymphoma (PTCL). Their benefit relative to combination chemotherapy remains undefined. Patients with histologically confirmed PTCL were enrolled in the Comprehensive Oncology Measures for Peripheral T-cell Lymphoma Treatment (COMPLETE) registry. Eligibility criteria included those with R/R disease who had received one prior systemic therapy and were given either a single agent or combination chemotherapy as first retreatment. Treatment results for those with R/R disease who received single agents were compared to those who received combination chemotherapy. The primary endpoint was best response to retreatment. Fifty-seven patients met eligibility criteria. At first retreatment, 46% (26/57) received combination therapy and 54.5% (31/57) received single agents. At median follow up of 2 years, a trend was seen towards increased complete response rate for single agents versus combination therapy (41% vs 19%; P = .02). There was also increased median overall survival (38.9 vs 17.1 months; P = .02) and progression-free survival (11.2 vs 6.7 months; P = .02). More patients receiving single agents received hematopoietic stem-cell transplantation (25.8% vs 7.7%, P = .07). Adverse events of grade 3 or 4 occurred more frequently in those receiving combination therapy, although this was not statistically significant. The data confirm the unmet need for better treatment in R/R PTCL. Despite a small sample, the analysis shows greater response and survival in those treated with single agents as first retreatment in R/R setting, while maintaining the ability to achieve transplantation. Large, randomized trials are needed to identify the best strategy.
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http://dx.doi.org/10.1002/ajh.25463DOI Listing
June 2019

A new target in CTCL: treating the skin, blood, and lymph nodes.

Authors:
Steven M Horwitz

Clin Adv Hematol Oncol 2019 Jan;17(1):40-43

Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, New York.

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January 2019

Active surveillance for nodular lymphocyte-predominant Hodgkin lymphoma.

Blood 2019 05 15;133(20):2121-2129. Epub 2019 Feb 15.

Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare subtype of lymphoma that, like other Hodgkin lymphomas, has historically been treated aggressively. However, in most cases, NLPHL has an indolent course, which raises the question of to what extent these patients require aggressive upfront treatment. We describe the management and outcomes of consecutive NLPHL patients diagnosed at Memorial Sloan Kettering Cancer Center (MSK), with a focus on evaluating active surveillance. All patients aged 16 years or older diagnosed and followed at MSK between 1974 and 2016 were included. Treatment outcomes were compared between management with active surveillance and other strategies. We identified 163 consecutive patients who were treated with radiotherapy alone (46%), active surveillance (23%), chemotherapy (16%), combined modality (12%), or rituximab monotherapy (4%). Median follow-up was 69 months. Five-year progression-free survival (PFS), second PFS (PFS2), and overall survival (OS) estimates were 85% (95% confidence interval [CI], 78-90), 97% (95% CI, 92-99), and 99% (95% CI, 95-100), respectively. Only 1 of 7 deaths was lymphoma related. Patients managed with active surveillance had slightly shorter PFS than those receiving any active treatment, with 5-year PFS of 77% (95% CI, 56-89) vs 87% (95% CI, 79-92; = .017). This difference did not translate into better PFS2 or OS. Only 10 patients managed with active surveillance (27%) eventually required treatment, after a median of 61 months, and none died. NLPHL has an excellent prognosis. Within the limitations of a retrospective analysis, active surveillance is a viable initial management strategy for selected NLPHL patients.
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http://dx.doi.org/10.1182/blood-2018-10-877761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7022227PMC
May 2019

Mycosis fungoides, Psoriasis und PD-1-Inhibitoren - neuer Aspekt einer bekannten Assoziation.

J Dtsch Dermatol Ges 2019 02;17(2):186-188

Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, and Weill Cornell Medicine, New York, NY, USA.

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http://dx.doi.org/10.1111/ddg.13715_gDOI Listing
February 2019