Durable Response to Brentuximab Vedotin-Based Chemotherapy in Refractory Hodgkin Lymphoma with Central Nervous System (CNS) Involvement

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Abstract

Patient: Female, 29-year-old

Final Diagnosis: Refractory Hodgkin lymphoma with CNS involvement

Symptoms: Blurred vision

Medication: —

Clinical Procedure: —

Specialty: Hematology

Objective:

Rare disease

Background:

CNS involvement in Hodgkin lymphoma is rare. Despite various treatment options, median overall survival is only 13 months after diagnosis of CNS involvement in relapsed/refractory HL.

Case Report:

A 29-year-old woman with classical HL (mixed cellularity) in clinical stage IIB was treated with multilineage chemotherapy and radiotherapy without achieving a sustained complete remission. Systemic and CNS progression of HL occurred at the age of 32 years and the patient received 2 cycles of brentuximab vedotin with bendamustine alternating with 2 cycles of high-dose methotrexate-based treatment and achieved partial remission. She then underwent autologous stem cell transplantation followed by brentuximab vedotin consolidation. The disease progressed and the patient died 6 months after the last dose of brentuximab vedotin.

Conclusions:

We demonstrated a durable response to brentuximab vedotin-based chemotherapy in a patient with refractory Hodgkin lymphoma with CNS involvement. Prognosis of these patients is poor and new treatment options are needed.

Related collections

Most cited references 6

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Combined immunochemotherapy with reduced whole-brain radiotherapy for newly diagnosed primary CNS lymphoma.

Jignesh Shah, Barbara Grant, David Schiff … (2007)

Our goals were to evaluate the safety of adding rituximab to methotrexate (MTX)-based chemotherapy for primary CNS lymphoma, determine whether additional cycles of induction chemotherapy improve the complete response (CR) rate, and examine effectiveness and toxicity of reduced-dose whole-brain radiotherapy (WBRT) after CR. Thirty patients (17 women; median age, 57 years; median Karnofsky performance score, 70) were treated with five to seven cycles of induction chemotherapy (rituximab, MTX, procarbazine, and vincristine [R-MPV]) as follows: day 1, rituximab 500 mg/m2; day 2, MTX 3.5 gm/m2 and vincristine 1.4 mg/m2. Procarbazine 100 mg/m2/d was administered for 7 days with odd-numbered cycles. Patients achieving CR received dose-reduced WBRT (23.4 Gy), and all others received standard WBRT (45 Gy). Two cycles of high-dose cytarabine were administered after WBRT. CSF levels of rituximab were assessed in selected patients, and prospective neurocognitive evaluations were performed. With a median follow-up of 37 months, 2-year overall and progression-free survival was 67% and 57%, respectively. Forty-four percent of patients achieved a CR after five or fewer cycles, and 78% after seven cycles. The overall response rate was 93%. Nineteen of 21 CR patients received the planned 23.4 Gy WBRT. The most commonly observed grade 3 to 4 toxicities included neutropenia (43%), thrombocytopenia (36%), and leukopenia (23%). No treatment-related neurotoxicity has been observed. The addition of rituximab to MPV increased the risk of significant neutropenia requiring routine growth factor support. Additional cycles of R-MPV nearly doubled the CR rate. Reduced-dose WBRT was not associated with neurocognitive decline, and disease control to date is excellent.

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Salvage therapy with bendamustine for methotrexate refractory recurrent primary CNS lymphoma: a retrospective case series.

Marc C. Chamberlain (2014)

There is comparatively limited therapy for recurrent primary central nervous system lymphoma (PCNSL). Salvage therapies include re-challenge with high-dose methotrexate (HD-MTX), whole brain radiotherapy, temozolomide, topotecan and premetrexed. Bendamustine is a novel bifunctional alkylator with established activity in B cell systemic lymphomas but never previously evaluated in PCNSL. The objective of the current study was to assess response and toxicity of bendamustine in recurrent PCNSL following prior salvage therapy in a retrospective case series. Twelve adults [six males; six females: median age 59 years (range 43-74)] with HD-MTX refractory recurrent PCNSL were treated with bendamustine. All patients were treated at second recurrence following failure of prior salvage therapy. A cycle of bendamustine was defined as two consecutive days of treatment (100 mg/m(2)/day) administered once every 4 weeks (maximum number of cycles 6). Toxicities seen were Grade 2 (24 episodes in 10 patients) and 3 (10 episodes in 5 patients) only and included lymphopenia (8 patients), hyperglycemia (7 patients), fatigue (7 patients) and nausea (4 patients). The median number of cycles of therapy was 3.5 (range 1-6). Radiographic response was progressive disease in 5 (42%), stable disease in 1 (8%), partial response in 3 (25%) and complete response in 3 (25%). Median progression free survival (PFS) was 3.5 months (range 1-14 months) and 6-month PFS was 33 %. In this small retrospective series of select patients with recurrent PCNSL refractory to HD-MTX, bendamustine appears to have modest single agent activity with manageable toxicity. Confirmation in a larger series of similar patients is required.

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Clinical characteristics and outcomes of patients with Hodgkin lymphoma with central nervous system involvement: An international multicenter collaboration.

Chan Y Cheah, Paul Bröckelmann, Dai Chihara … (2016)

Central nervous system (CNS) involvement is rare in patients with Hodgkin lymphoma (HL). Thus, the clinical features and outcomes are not well described. Cases of histologically confirmed CNS HL diagnosed between 1995 and 2015 were retrospectively identified in institutional (n = 7), national (n = 2), and cooperative group (n = 1) databases. We screened 30,781 patients with HL in our combined databases and identified 21 patients meeting eligibility criteria, an estimated frequency of 0.07%. CNS involvement was present at initial diagnosis in 10 patients (48%) and a feature of relapsed/refractory disease in 11 (52%). Among these 11 patients, the median time from initial diagnosis of HL to development of CNS involvement was 1.9 years (range 0.4-6.6) and the median number of prior lines of therapy was 2 (range 1-7). Altogether, treatments included radiation, multiagent systemic chemotherapy, combined modality therapy, and subtotal resection. The overall response rate was 65%. After a median follow-up of 3.6 years (range 0.8-13.2) from diagnosis of CNS HL, the median PFS and OS were 7.6 and 29 months, respectively. CNS involvement as a feature of relapsed/refractory disease was adversely prognostic for both PFS and OS; however, four patients remain alive and free of relapse at 7-78 months follow-up. CNS involvement in HL is exceedingly rare and has a distinct clinical presentation with predilection for parenchymal lesions with dural extension. Around one-quarter of patients, mostly with CNS involvement at initial HL diagnosis, experience prolonged disease-free survival. Am. J. Hematol. 91:894-899, 2016. © 2016 Wiley Periodicals, Inc.

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Author and article information

Journal

Journal ID (nlm-ta): Am J Case Rep

Journal ID (iso-abbrev): Am J Case Rep

Journal ID (publisher-id): amjcaserep

Title: The American Journal of Case Reports

Publisher: International Scientific Literature, Inc.

ISSN (Electronic): 1941-5923

Publication date Collection: 2020

Publication date (Electronic): 14 March 2020

Volume: 21

Pages: e921657-1-e921657-4

Affiliations

[1 ]Department of Internal Medicine and Hematology, Faculty Hospital KralovskeVinohrady and Third Faculty of Medicine, Charles University in Prague, Prague, Czech Republic

[2 ]Department of Radiology, Faculty Hospital Kralovske Vinohrady and Third Faculty of Medicine, Charles University in Prague, Prague, Czech Republic

[3 ]Department of Medical Oncology and Hematology, Misurata Cancer Center, Misurata, Lybia

[4 ]Institute of Pathology and Molecular Medicine, University Hospital Motol, Prague, Czech Republic

Author notes

Corresponding Author: Heidi Mociková, e-mail: heidi.mocikova@ 123456seznam.cz

Authors’ Contribution:

[A]

Study Design

[B]

Data Collection

[C]

Statistical Analysis

[D]

Data Interpretation

[E]

Manuscript Preparation

[F]

Literature Search

[G]

Funds Collection

Conflict of interest: None declared

Source of supprt:

This work was supported by the Ministry of Health of the Czech Republic under grant AZV 16-29857A and by Research project Q 28 awarded by Charles University in Prague, Third Faculty of Medicine (Prague)

Article

Publisher ID: 921657

DOI: 10.12659/AJCR.921657

PMC ID: 7083218

PubMed ID: 32170052

SO-VID: 2bccd7e7-439e-495d-bedd-2b056e2d9bc1

License:

This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International ( CC BY-NC-ND 4.0)

History

Date received : 24 November 2019

Date accepted : 11 January 2020

Date revision received : 29 January 2020

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Durable Response to Brentuximab Vedotin-Based Chemotherapy in Refractory Hodgkin Lymphoma with Central Nervous System (CNS) Involvement

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Abstract

Objective:

Background:

Case Report:

Conclusions:

Related collections

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Most cited references 6

Combined immunochemotherapy with reduced whole-brain radiotherapy for newly diagnosed primary CNS lymphoma.

Salvage therapy with bendamustine for methotrexate refractory recurrent primary CNS lymphoma: a retrospective case series.

Clinical characteristics and outcomes of patients with Hodgkin lymphoma with central nervous system involvement: An international multicenter collaboration.

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