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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

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

The percentage of CD8+ T cells in lymphocyte subgroups at peripheral blood before and during treatment with pembrolizumab.Notes: During treatment with pembrolizumab, CD8+ T cell levels rapidly increased and reached an initial peak after two cycles (2 mg/kg every 3 weeks). At that time, the patient’s clinical symptoms were relieved. As the patient was diagnosed with serious pneumonitis, the dose of subsequent treatments was reduced to 1 mg/kg every 3 weeks. Unexpectedly, after two cycles at 2 mg/kg and two cycles at 1 mg/kg, the patient’s high level of CD8+ T cells was maintained. During that time, there was a dramatic reduction in total tumor burden. After she received six cycles of pembrolizumab, the patient achieved VGPR. During this period, the patient’s cytotoxic T cell levels reached another peak, which was higher than the previous one.Abbreviation: VGPR, very good partial response.
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f4-ott-9-5781: The percentage of CD8+ T cells in lymphocyte subgroups at peripheral blood before and during treatment with pembrolizumab.Notes: During treatment with pembrolizumab, CD8+ T cell levels rapidly increased and reached an initial peak after two cycles (2 mg/kg every 3 weeks). At that time, the patient’s clinical symptoms were relieved. As the patient was diagnosed with serious pneumonitis, the dose of subsequent treatments was reduced to 1 mg/kg every 3 weeks. Unexpectedly, after two cycles at 2 mg/kg and two cycles at 1 mg/kg, the patient’s high level of CD8+ T cells was maintained. During that time, there was a dramatic reduction in total tumor burden. After she received six cycles of pembrolizumab, the patient achieved VGPR. During this period, the patient’s cytotoxic T cell levels reached another peak, which was higher than the previous one.Abbreviation: VGPR, very good partial response.

Mentions: In previously reported clinical trials, increased lactate dehydrogenase (LDH) levels during the treatment with pembrolizumab were reported iñ30% of patients.16,17 In HL, LDH testing is a mandatory laboratory test as it is a factor associated with disease staging, prognosis, and response. However, the patient’s LDH level in this report was mainly in the normal range (Figure 3). As pembrolizumab promotes cytotoxic T-cell activity and suppresses the function of regulatory T cells, the lymphocyte subgroups of the patient’s peripheral blood were dynamically monitored. During treatment with pembrolizumab, the levels of CD8+ T cells rapidly increased and a peak in levels was observed after the initial two cycles (2 mg/kg every 3 weeks) (Figure 4). During that time, the patient experienced relief of clinical symptoms. Due to a case of severe pneumonitis, the dose was reduced to 1 mg/kg every 3 weeks for subsequent treatments. Unexpectedly, after two cycles at 2 mg/kg and two cycles at 1 mg/kg, the CD8+ T-cell level did not decrease (Figure 4). In addition, the total tumor burden was dramatically reduced (Figure 5). Following six cycles of pembrolizumab, the patient achieved VGPR. During this period, cytotoxic T cells reached another peak that was higher than the previous one (Figure 4). In this case, the increased level of CD8+ T cells correlated with therapeutic efficacy.


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
The percentage of CD8+ T cells in lymphocyte subgroups at peripheral blood before and during treatment with pembrolizumab.Notes: During treatment with pembrolizumab, CD8+ T cell levels rapidly increased and reached an initial peak after two cycles (2 mg/kg every 3 weeks). At that time, the patient’s clinical symptoms were relieved. As the patient was diagnosed with serious pneumonitis, the dose of subsequent treatments was reduced to 1 mg/kg every 3 weeks. Unexpectedly, after two cycles at 2 mg/kg and two cycles at 1 mg/kg, the patient’s high level of CD8+ T cells was maintained. During that time, there was a dramatic reduction in total tumor burden. After she received six cycles of pembrolizumab, the patient achieved VGPR. During this period, the patient’s cytotoxic T cell levels reached another peak, which was higher than the previous one.Abbreviation: VGPR, very good partial response.
© Copyright Policy
Related In: Results  -  Collection

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

f4-ott-9-5781: The percentage of CD8+ T cells in lymphocyte subgroups at peripheral blood before and during treatment with pembrolizumab.Notes: During treatment with pembrolizumab, CD8+ T cell levels rapidly increased and reached an initial peak after two cycles (2 mg/kg every 3 weeks). At that time, the patient’s clinical symptoms were relieved. As the patient was diagnosed with serious pneumonitis, the dose of subsequent treatments was reduced to 1 mg/kg every 3 weeks. Unexpectedly, after two cycles at 2 mg/kg and two cycles at 1 mg/kg, the patient’s high level of CD8+ T cells was maintained. During that time, there was a dramatic reduction in total tumor burden. After she received six cycles of pembrolizumab, the patient achieved VGPR. During this period, the patient’s cytotoxic T cell levels reached another peak, which was higher than the previous one.Abbreviation: VGPR, very good partial response.
Mentions: In previously reported clinical trials, increased lactate dehydrogenase (LDH) levels during the treatment with pembrolizumab were reported iñ30% of patients.16,17 In HL, LDH testing is a mandatory laboratory test as it is a factor associated with disease staging, prognosis, and response. However, the patient’s LDH level in this report was mainly in the normal range (Figure 3). As pembrolizumab promotes cytotoxic T-cell activity and suppresses the function of regulatory T cells, the lymphocyte subgroups of the patient’s peripheral blood were dynamically monitored. During treatment with pembrolizumab, the levels of CD8+ T cells rapidly increased and a peak in levels was observed after the initial two cycles (2 mg/kg every 3 weeks) (Figure 4). During that time, the patient experienced relief of clinical symptoms. Due to a case of severe pneumonitis, the dose was reduced to 1 mg/kg every 3 weeks for subsequent treatments. Unexpectedly, after two cycles at 2 mg/kg and two cycles at 1 mg/kg, the CD8+ T-cell level did not decrease (Figure 4). In addition, the total tumor burden was dramatically reduced (Figure 5). Following six cycles of pembrolizumab, the patient achieved VGPR. During this period, cytotoxic T cells reached another peak that was higher than the previous one (Figure 4). In this case, the increased level of CD8+ T cells correlated with therapeutic efficacy.

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