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A case report and literature review of primary resistant Hodgkin lymphoma: a response to anti-PD-1 after failure of autologous stem cell transplantation and brentuximab vedotin

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ABSTRACT

Hodgkin lymphoma (HL) is a highly curable hematologic malignancy, and ~70% of cases can be cured with combination chemotherapy with or without radiation. However, patients with primary resistant disease have a cure rate of <30%. For such patients, high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is considered to be the standard treatment. If patients fail to respond to ASCT or relapse soon thereafter, they usually receive another ASCT, allogeneic stem cell transplantation or treatment with novel agents. This case report presents the case of a 54-year-old patient with primary resistant HL who received single-agent treatment, brentuximab vedotin, after ASCT relapse. Despite treatment with brentuximab vedotin, the disease continued to progress. In patients with such highly resistant disease, the treatment options are limited. Depending on the physical condition and the willingness of the patient, pembrolizumab, a programmed cell death protein-1 inhibitor, can be given as salvage therapy. But, out of our expectation, the patient achieved a very good partial response after four cycles of pembrolizumab. No serious adverse events were observed with pembrolizumab treatment. This case provides support for a new and effective strategy for treating primary resistant Hodgkin lymphoma.

No MeSH data available.


Related in: MedlinePlus

Pathology and immunohistochemistry.Notes: (A) The arrow points to Hodgkin lymphoma cells expressing CD30. The image was obtained by staining CD30 when the disease was diagnosed in May 2012. (B) The arrow points to Hodgkin Reed–Sternberg cells surrounded by a large number of inflammatory and immune cells in an involved lymph node. The image was obtained from the initial involved lymph node. (C) The arrow points to the large cells expressing CD30 admixed with lymphocyte cells. These larger cells also expressed CD15, but we could not exclude the possibility of lung involvement. However, the patient exhibited classical B symptoms and experienced recurrence with incomplete remission. According to the PET/CT examination, the disease was classified as stage IV B lymphoma in September 2013. (D) After ASCT failure, the patient received six cycles of brentuximab vedotin treatment. However, the disease progressed after these therapies in April 2014. Then, through fiberoptic bronchoscopy lesion biopsy, the patient's multiple bilateral pulmonary lesions were diagnosed with involved classical Hodgkin lymphoma cells. Magnification (A and B) is 40×10 and (C and D) is 100×10.Abbreviations: ASCT, autologous stem cell transplantation; CT, computed tomography; PET, positron emission tomography.
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f1-ott-9-5781: Pathology and immunohistochemistry.Notes: (A) The arrow points to Hodgkin lymphoma cells expressing CD30. The image was obtained by staining CD30 when the disease was diagnosed in May 2012. (B) The arrow points to Hodgkin Reed–Sternberg cells surrounded by a large number of inflammatory and immune cells in an involved lymph node. The image was obtained from the initial involved lymph node. (C) The arrow points to the large cells expressing CD30 admixed with lymphocyte cells. These larger cells also expressed CD15, but we could not exclude the possibility of lung involvement. However, the patient exhibited classical B symptoms and experienced recurrence with incomplete remission. According to the PET/CT examination, the disease was classified as stage IV B lymphoma in September 2013. (D) After ASCT failure, the patient received six cycles of brentuximab vedotin treatment. However, the disease progressed after these therapies in April 2014. Then, through fiberoptic bronchoscopy lesion biopsy, the patient's multiple bilateral pulmonary lesions were diagnosed with involved classical Hodgkin lymphoma cells. Magnification (A and B) is 40×10 and (C and D) is 100×10.Abbreviations: ASCT, autologous stem cell transplantation; CT, computed tomography; PET, positron emission tomography.

Mentions: A 54-year-old female was diagnosed with classical HL (Figure 1) involving her neck, mediastinal, and left hilus pulmonis lymph nodes corresponding to stage IIB (fever) in May 2012. According to the German Hodgkin Study Group classification system, the patient was considered to have advanced HL as the erythrocyte sedimentation rate was >30 mm/h with B symptoms and more than two regional lymph nodes were invaded, without extranodal involvement as assessed by positron emission tomography (PET)/computed tomography (CT) (Figure 2). On the basis of the National Comprehensive Cancer Network clinical guidelines for the treatment of HL, the patient received four cycles of ABVD (doxorubicin, bleomycin, vincristine, and dacarbazine). Following ABVD treatment, the patient experienced relief of clinical symptoms (fever and cough). In addition, the neck and right hilus pulmonis lymph nodes had decreased in size. Although the mediastinal lymph nodes had also diminished, PET/CT revealed that their metabolic activity had not decreased obviously or detectably (Figure 2). Moreover, PET/CT also identified that the seventh right rib was a new zone of increased metabolism compared with the initial scan.


A case report and literature review of primary resistant Hodgkin lymphoma: a response to anti-PD-1 after failure of autologous stem cell transplantation and brentuximab vedotin
Pathology and immunohistochemistry.Notes: (A) The arrow points to Hodgkin lymphoma cells expressing CD30. The image was obtained by staining CD30 when the disease was diagnosed in May 2012. (B) The arrow points to Hodgkin Reed–Sternberg cells surrounded by a large number of inflammatory and immune cells in an involved lymph node. The image was obtained from the initial involved lymph node. (C) The arrow points to the large cells expressing CD30 admixed with lymphocyte cells. These larger cells also expressed CD15, but we could not exclude the possibility of lung involvement. However, the patient exhibited classical B symptoms and experienced recurrence with incomplete remission. According to the PET/CT examination, the disease was classified as stage IV B lymphoma in September 2013. (D) After ASCT failure, the patient received six cycles of brentuximab vedotin treatment. However, the disease progressed after these therapies in April 2014. Then, through fiberoptic bronchoscopy lesion biopsy, the patient's multiple bilateral pulmonary lesions were diagnosed with involved classical Hodgkin lymphoma cells. Magnification (A and B) is 40×10 and (C and D) is 100×10.Abbreviations: ASCT, autologous stem cell transplantation; CT, computed tomography; PET, positron emission tomography.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5036553&req=5

f1-ott-9-5781: Pathology and immunohistochemistry.Notes: (A) The arrow points to Hodgkin lymphoma cells expressing CD30. The image was obtained by staining CD30 when the disease was diagnosed in May 2012. (B) The arrow points to Hodgkin Reed–Sternberg cells surrounded by a large number of inflammatory and immune cells in an involved lymph node. The image was obtained from the initial involved lymph node. (C) The arrow points to the large cells expressing CD30 admixed with lymphocyte cells. These larger cells also expressed CD15, but we could not exclude the possibility of lung involvement. However, the patient exhibited classical B symptoms and experienced recurrence with incomplete remission. According to the PET/CT examination, the disease was classified as stage IV B lymphoma in September 2013. (D) After ASCT failure, the patient received six cycles of brentuximab vedotin treatment. However, the disease progressed after these therapies in April 2014. Then, through fiberoptic bronchoscopy lesion biopsy, the patient's multiple bilateral pulmonary lesions were diagnosed with involved classical Hodgkin lymphoma cells. Magnification (A and B) is 40×10 and (C and D) is 100×10.Abbreviations: ASCT, autologous stem cell transplantation; CT, computed tomography; PET, positron emission tomography.
Mentions: A 54-year-old female was diagnosed with classical HL (Figure 1) involving her neck, mediastinal, and left hilus pulmonis lymph nodes corresponding to stage IIB (fever) in May 2012. According to the German Hodgkin Study Group classification system, the patient was considered to have advanced HL as the erythrocyte sedimentation rate was >30 mm/h with B symptoms and more than two regional lymph nodes were invaded, without extranodal involvement as assessed by positron emission tomography (PET)/computed tomography (CT) (Figure 2). On the basis of the National Comprehensive Cancer Network clinical guidelines for the treatment of HL, the patient received four cycles of ABVD (doxorubicin, bleomycin, vincristine, and dacarbazine). Following ABVD treatment, the patient experienced relief of clinical symptoms (fever and cough). In addition, the neck and right hilus pulmonis lymph nodes had decreased in size. Although the mediastinal lymph nodes had also diminished, PET/CT revealed that their metabolic activity had not decreased obviously or detectably (Figure 2). Moreover, PET/CT also identified that the seventh right rib was a new zone of increased metabolism compared with the initial scan.

View Article: PubMed Central - PubMed

ABSTRACT

Hodgkin lymphoma (HL) is a highly curable hematologic malignancy, and ~70% of cases can be cured with combination chemotherapy with or without radiation. However, patients with primary resistant disease have a cure rate of <30%. For such patients, high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is considered to be the standard treatment. If patients fail to respond to ASCT or relapse soon thereafter, they usually receive another ASCT, allogeneic stem cell transplantation or treatment with novel agents. This case report presents the case of a 54-year-old patient with primary resistant HL who received single-agent treatment, brentuximab vedotin, after ASCT relapse. Despite treatment with brentuximab vedotin, the disease continued to progress. In patients with such highly resistant disease, the treatment options are limited. Depending on the physical condition and the willingness of the patient, pembrolizumab, a programmed cell death protein-1 inhibitor, can be given as salvage therapy. But, out of our expectation, the patient achieved a very good partial response after four cycles of pembrolizumab. No serious adverse events were observed with pembrolizumab treatment. This case provides support for a new and effective strategy for treating primary resistant Hodgkin lymphoma.

No MeSH data available.


Related in: MedlinePlus