Use of ifosfamide, carboplatin and etoposide in combination with brentuximab vedotin or romidepsin based on CD30 positivity in relapsed/refractory peripheral T‐cell lymphoma

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Abstract

Background

Relapsed/refractory peripheral T‐cell lymphoma (R/R PTCL) has a poor prognosis. Romidepsin (Ro) and brentuximab vedotin (Bv), combined with ifosfamide, carboplatin, and etoposide (ICE) has not been significantly studied in PTCL.

Aim

We report outcomes of Bv‐ICE in CD30 (+) and Ro‐ICE in CD30 (−) R/R PTCL treated in “Blinded for peer review” Cancer Center.

Methods and Results

We retrospectively identified R/R PTCL patients treated with BV‐ICE or romidepsin‐ICE from May 2016 to September 2019. Out of 13 R/R PTCL patients, 6 were treated with Bv‐ICE and 7 with Ro‐ICE. Bv‐ICE had an overall response rate (ORR) of 66.7%, with all the patients achieving a complete response. ORR was 71.4% for Ro‐ICE with 57.1% of patients achieving a complete response. Two patients treated with Bv‐ICE and three treated with Ro‐ICE received transplantation.

Conclusion

In our experience, treatment with Bv‐ICE and Ro‐ICE based on CD30 positivity is feasible and effective to treat patients with R/R PTCL.

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Most cited references 21

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Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large-cell lymphoma: results of a phase II study.

Maurice L. Sievers, Michelle Fanale, Jeffrey Matous … (2012)

Systemic anaplastic large-cell lymphoma (ALCL) is an aggressive subtype of T-cell lymphoma characterized by the uniform expression of CD30. The antibody-drug conjugate brentuximab vedotin delivers the potent antimicrotubule agent monomethylauristatin E to CD30-positive malignant cells. A phase II multicenter trial was conducted to evaluate the efficacy and safety of brentuximab vedotin in patients with relapsed or refractory systemic ALCL. Patients with systemic ALCL and recurrent disease after at least one prior therapy received brentuximab vedotin 1.8 mg/kg intravenously every 3 weeks over 30 minutes as an outpatient infusion. The primary end point of the study was overall objective response rate as assessed by independent central review. Of 58 patients treated in the study, 50 patients (86%) achieved an objective response, 33 patients (57%) achieved a complete remission (CR), and 17 patients (29%) achieved a partial remission. The median durations of overall response and CR were 12.6 and 13.2 months, respectively. Grade 3 or 4 adverse events in ≥ 10% of patients were neutropenia (21%), thrombocytopenia (14%), and peripheral sensory neuropathy (12%). Brentuximab vedotin induced objective responses in the majority of patients and CRs in more than half of patients with recurrent systemic ALCL. Targeted therapy with this CD30-directed antibody-drug conjugate may be an effective treatment for relapsed or refractory systemic ALCL and warrants further studies in front-line therapy.

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Results from a pivotal, open-label, phase II study of romidepsin in relapsed or refractory peripheral T-cell lymphoma after prior systemic therapy.

Bertrand Coiffier, Barbara Pro, H Miles Prince … (2012)

Romidepsin is a structurally unique, potent class 1 selective histone deacetylase inhibitor. The primary objective of this international, pivotal, single-arm, phase II trial was to confirm the efficacy of romidepsin in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). Patients who were refractory to at least one prior systemic therapy or for whom at least one prior systemic therapy failed received romidepsin at 14 mg/m(2) as a 4-hour intravenous infusion on days 1, 8, and 15 every 28 days. The primary end point was the rate of complete response/unconfirmed complete response (CR/CRu) as assessed by an independent review committee. Of the 131 patients enrolled, 130 had histologically confirmed PTCL by central review. The median number of prior systemic therapies was two (range, one to eight). The objective response rate was 25% (33 of 130), including 15% (19 of 130) with CR/CRu. Patient characteristics, prior stem-cell transplantation, number or type of prior therapies, or response to last prior therapy did not have an impact on response rate. The median duration of response was 17 months, with the longest response ongoing at 34+ months. Of the 19 patients who achieved CR/CRu, 17 (89%) had not experienced disease progression at a median follow-up of 13.4 months. The most common grade ≥ 3 adverse events were thrombocytopenia (24%), neutropenia (20%), and infections (all types, 19%). Single-agent romidepsin induced complete and durable responses with manageable toxicity in patients with relapsed or refractory PTCL across all major PTCL subtypes, regardless of the number or type of prior therapies. Results led to US Food and Drug Administration approval of romidepsin in this indication.

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Survival of patients with peripheral T-cell lymphoma after first relapse or progression: spectrum of disease and rare long-term survivors.

Diego Villa, T Shenkier, L Sehn … (2013)

A number of novel therapies are under investigation in relapsed or refractory peripheral T-cell lymphoma (PTCL); however, their relative impact on outcome is unknown. We examined the survival of patients with PTCL after relapse or progression in the absence of hematopoietic stem-cell transplantation and explored factors influencing survival. The three most common subtypes encountered in North America were evaluated: PTCL not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), and anaplastic large-cell lymphoma (ALCL; anaplastic lymphoma kinase [ALK] positive and ALK negative. After exclusions, 153 patients were analyzed (PTCL-NOS, n = 79 [52%]; AITL, n = 38 [25%]; ALK-positive ALCL, n = 11 [7%]; ALK-negative ALCL, n = 27 [16%; including ALK status unknown, n = 1]). Median time from initial diagnosis to relapse or progression after primary therapy was 6.7 months, and median age at relapse was 66 years (ALK-positive ALCL, 39 years). Median overall survival (OS) and median progression-free survival (PFS) after relapse or progression (second PFS) were 5.5 and 3.1 months, respectively, and were only marginally better in patients who received chemotherapy at relapse (n = 89 [58%]; 6.5 and 3.7 months, respectively). Patients with good performance status (PS) of 0 or 1 (n = 47) at relapse who received chemotherapy had a more favorable OS (P < .001; median OS, 13.7 months) and PFS (P = .006; median second PFS, 5.0 months), which remained significant in multivariate analysis (OS: hazard ratio [HR], 2.09; P = .002; second PFS: HR, 1.66; P = .030). Most patients with relapsed or refractory PTCL have poor outcomes with short survival. Select patients with good PS have more favorable outcomes with standard chemotherapy.

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Author and article information

Contributors

Cesar Gentille:

ORCID: https://orcid.org/0000-0001-7643-8154

cggentille@gmail.com

Journal

Journal ID (nlm-ta): Cancer Rep (Hoboken)

Journal ID (iso-abbrev): Cancer Rep (Hoboken)

Journal ID (doi): 10.1002/(ISSN)2573-8348

Journal ID (publisher-id): CNR2

Title: Cancer Reports

Publisher: John Wiley and Sons Inc. (Hoboken )

ISSN (Electronic): 2573-8348

Publication date (Electronic): 08 March 2022

Publication date Collection: July 2022

Volume: 5

Issue: 7 ( doiID: 10.1002/cnr2.v5.7 )

Electronic Location Identifier: e1581

Affiliations

[ ¹ ] Houston Methodist Cancer Center Houston Texas USA

[ ² ] Houston Methodist Hospital Houston Texas USA

Author notes

[*] [* ] Correspondence

Cesar Gentille, Houston Methodist Cancer Center, Houston, TX 77030, USA.

Email: cggentille@ 123456gmail.com

Author information

Cesar Gentille https://orcid.org/0000-0001-7643-8154

Article

Publisher ID: CNR21581

DOI: 10.1002/cnr2.1581

PMC ID: 9327648

PubMed ID: 35263030

SO-VID: 6332f054-90d1-4c1d-bcd3-eba4eda78897

License:

This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

History

Date revision received : 31 August 2021

Date received : 16 April 2021

Date accepted : 12 October 2021

Page count

Figures: 0, Tables: 2, Pages: 5, Words: 3331

Custom metadata

source-schema-version-number 2.0

cover-date July 2022

details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:6.1.7 mode:remove_FC converted:27.07.2022

Keywords: brentuximab vedotin,ice,relapsed/refractory ptcl,romidepsin,salvage chemotherapy

Data availability:

Keywords: brentuximab vedotin, ice, relapsed/refractory ptcl, romidepsin, salvage chemotherapy

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Use of ifosfamide, carboplatin and etoposide in combination with brentuximab vedotin or romidepsin based on CD30 positivity in relapsed/refractory peripheral T‐cell lymphoma

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Abstract

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Methods and Results

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Gamma Delta T cells

Most cited references 21

Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large-cell lymphoma: results of a phase II study.

Results from a pivotal, open-label, phase II study of romidepsin in relapsed or refractory peripheral T-cell lymphoma after prior systemic therapy.

Survival of patients with peripheral T-cell lymphoma after first relapse or progression: spectrum of disease and rare long-term survivors.

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