Phase II trial of dose-adjusted EPOCH in untreated systemic anaplastic large cell lymphoma

Dunleavy, Kieron; Pittaluga, Stefania; Shovlin, Margaret; Roschewski, Mark; Lai, Catherine; Steinberg, Seth M.; Jaffe, Elaine S.; Wilson, Wyndham H.

doi:10.3324/haematol.2015.131151

Cited by 25 publications

(23 citation statements)

References 15 publications

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“…An anthracycline based combination chemotherapy regimen like CHOP results in ORR of 80% to 85%. In younger patients the addition of etoposide to CHOP and similar infusional regimens have produced excellent responses in ALCL and a 12‐year OS of over 70% regardless of ALK status. First line therapy cures 3/4 of the patients with ALK+ ALCL and consolidative transplants are not recommended for this group of patients if they have a low IPI of 0 to 2 .…”

Section: Molecular Pathogenesis Of Ptcl Subtypesmentioning

confidence: 99%

Aggressive T‐cell lymphomas: 2019 updates on diagnosis, risk stratification, and management

Zain

2019

American J Hematol

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Introduction Aggressive T‐cell lymphomas continue to have a poor prognosis. There are over 27 different subtypes of peripheral T‐cell lymphoma (PTCL) and we are now beginning to understand the differences between the various subtypes beyond histologic variations. Molecular pathogenesis of various subtypes of PTCL Gene expression profiling can help in diagnosis and prognostication of various subtypes including PTCL‐nos and anaplastic large cell lymphoma. In addition, mutational analysis is now being incorporated in clinical trials of novel agents to evaluate various biomarkers of response to allow better therapeutic choices for patients. Targeted therapies There are many targeted agents currently in various stages of clinical trials for PTCL that take advantage of the differential expression of specific proteins or receptors in PTCL tumors. The most promising is the CD30 directed antibody drug conjugate brentuximab vedotin. This has recently been approved by the Food and Drug Administration for the upfront treatment of CD30 expressing PTCLs in combination with cyclophosphamide, doxorubicin, and prednisone chemotherapy. Other notable targets are CD25, CCR4 tag, PI3kinase inhibitors, and JAK/STAT inhibitors. Anaplastic lymphoma kinase (ALK) inhibitors are promising for ALK expressing tumors. Immunotherapies The use of checkpoint inhibitors in the treatment of PTCL is still controversial. The most promising results have been seen in cases of extranodal natural killer cell/T‐cell lymphomas and cutaneous T‐cell lymphomas. For all other subtypes, immune checkpoint inhibitors should be used with extreme caution and only in the context of a clinical trial. Allogeneic stem cell transplant continues to be the curative therapy for most aggressive subtypes of PTCL.

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Section: Molecular Pathogenesis Of Ptcl Subtypesmentioning

confidence: 99%

Aggressive T‐cell lymphomas: 2019 updates on diagnosis, risk stratification, and management

Zain

2019

American J Hematol

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“…In general, ALK-positive ALCL is associated with better clinical outcomes than ALKnegative ALCL, PTCL-NOS, or AITL, although the favorable prognosis of ALK-1 positivity decreases with older age and higher prognostic risk scores. [18][19][20][21] First-line consolidation with high-dose therapy followed by autologous stem cell rescue (HDT/ASCR) is associated with improved outcomes in patients who experience a good response to induction therapy. However, except for those with ALK-positive ALCL, outcomes are disappointing for patients with the most common forms of PTCLs, namely PTCL-NOS and AITL, compared with the favorable results achieved with DLBCL.…”

Section: Overviewmentioning

confidence: 99%

NCCN Guidelines Insights: Non-Hodgkin's Lymphomas, Version 3.2016

Horwitz

Zelenetz

Gordon³

et al. 2016

J Natl Compr Canc Netw

115

120

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Peripheral T-cell lymphomas (PTCLs) represent a relatively uncommon heterogeneous group of non-Hodgkin's lymphomas (NHLs) with an aggressive clinical course and poor prognosis. Anthracycline-based multiagent chemotherapy with or without radiation therapy followed by first-line consolidation with high-dose therapy followed by autologous stem cell rescue (HDT/ASCR) is the standard approach to most of the patients with newly diagnosed PTCL. Relapsed or refractory disease is managed with second-line systemic therapy followed by HDT/ASCR or allogeneic stem cell transplant, based on the patient's eligibility for transplant. In recent years, several newer agents have shown significant activity in patients with relapsed or refractory disease across all 4 subtypes of PTCL. These NCCN Guideline Insights highlight the important updates to the NCCN Guidelines for NHL, specific to the management of patients with relapsed or refractory PTCL.

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“…reported the encouraging results of a phase II trial of dose-adjusted EPOCH in 24 patients with untreated ALK-positive (n=15) and ALK-negative (n=9) ALCL. 15 The event-free survival (EFS) in ALK-positive and ALK-negative ALCL was 72.0% and 62.5%, respectively, and the OS was 78.0% and 87.5% at a median potential follow up of 14.4 years. Based on the hypothesis that dose-adjusted EPOCH may improve treatment outcome, we undertook a phase II prospective study of dose-adjusted EPOCH in patients with nodal PTCL.…”

Section: Introductionmentioning

confidence: 98%

Dose-adjusted EPOCH chemotherapy for untreated peripheral T-cell lymphomas: a multicenter phase II trial of West-JHOG PTCL0707

et al. 2017

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The standard CHOP therapy for peripheral T-cell lymphoma has resulted in unsatisfactory outcomes and it is still not clear what is the optimal front-line therapy. We conducted a multicenter phase II study of dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine and prednisone (EPOCH) for untreated peripheral T-cell lymphoma patients. In this prospective study, 41 patients were treated with dose-adjusted-EPOCH as initial therapy: peripheral T-cell lymphoma-not otherwise specified, n=21; angioimmunoblastic T-cell lymphoma, n=17; anaplastic lymphoma kinase-positive anaplastic large cell lymphoma, n=2; and anaplastic lymphoma kinase-negative anaplastic large cell lymphoma, n=1. Median patient age was 64 years (range: 32–79 years). According to the International Prognostic Index criteria, 51.2% were at high-intermediate or high risk. The overall response and complete response rates were 78.0% [95% confidence interval (CI): 62.4–89.4%] and 61.0% (95%CI: 44.5–75.8%), respectively. At the median follow up of 24.0 months, the 2-year progression-free survival and overall survival were 53.3% (95%CI: 36.4–67.5%) and 73.2% (95%CI: 56.8–84.1%), respectively. The younger patients (≤ 60 years old) had a high response rate (overall response 94.1% and complete response 70.6%) and survival rate (progression-free survival 62.5% and overall survival 82.4%). The most common grade ≥ 3 adverse events were neutropenia (74.5%), anemia (40.8%), thrombocytopenia (22.0%), and febrile neutropenia (9.0%). Dose-adjusted-EPOCH had a high response rate with a tolerable toxicity profile. Our results indicate that dose-adjusted-EPOCH is a reasonable first-line approach for peripheral T-cell lymphoma patients and may improve outcomes.

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Phase II trial of dose-adjusted EPOCH in untreated systemic anaplastic large cell lymphoma

Cited by 25 publications

References 15 publications

Aggressive T‐cell lymphomas: 2019 updates on diagnosis, risk stratification, and management

Aggressive T‐cell lymphomas: 2019 updates on diagnosis, risk stratification, and management

NCCN Guidelines Insights: Non-Hodgkin's Lymphomas, Version 3.2016

Dose-adjusted EPOCH chemotherapy for untreated peripheral T-cell lymphomas: a multicenter phase II trial of West-JHOG PTCL0707

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