Contributions
Abstract: PB2021
Type: Publication Only
Background
Hemophagocytic lymphohistiocytosis (HLH) is an infrequent but potentially life-threatening hyperinflammatory syndrome that occurs in about 6% of patients affected by Hodgkin Lymphoma. Treatment of secondary HLH includes corticosteroids, cyclosporine A, etoposide and/ or malignancy-directed therapies. Anecdotal cases report successful results with Alemtuzumab, Infliximab, Daclizumab, Blinatumomab and Ruxolitinib.
Aims
We describe a case of HLH complicating refractory classical Hodgkin lymphoma (cHL) that resolved only after treatment with Nivolumab. At our knowledge, this is the first case reported.
Methods
A 21-year-old man was diagnosed with cHL, CS IIIB, in September 2014. He was refractory to five lines of treatment (ABVD, IGEV, Brentuximab Vedotin, Bendamustine and Beacopp). In April 2016 he developed fever, marked splenomegaly and grade 4 pancytopenia. Other laboratory findings showed hypoalbuminemia, hypertransaminasemia and hyperbilirubinemia; antibody tests for HCV, HBV, HIV, HSV, CMV and EBV infections were negative. The bone marrow biopsy showed the presence of numerous macrophages embedding hematopoietic elements, without lymphoma infiltration. Consequently, HLH was diagnosed. Treatment with corticosteroids and etoposide was ineffective. In May 2016 he started treatment with Nivolumab (in the setting of the Italian Extented Access Program) at the dose of 3 mg/kg every 14 days.
Results
Until Nivolumab treatment was started the patient required transfusion support with 14 PRBC Units and 19 Plt Units. After the first administration of Nivolumab he developed an episode of respiratory insufficiency infusion related that resolved with mild corticosteroid therapy. The patient became transfusion independent after the third dose of Nivolumab. After 32 doses of Nivolumab, in November 2017 treatment was stopped because of a severe pancreatitis treatment related. Unfortunately in February 2018 the patient died in complete remission in a road accident.
Conclusion
HLH is a potentially fatal hyperinflammatory disease induced by a pathologic immune activation, with proliferation of well-differentiated macrophages/histiocytes and increased phagocytic activity. The tumor in cHL is mainly composed of inflammatory cells providing a protective niche to the sparse CD30-positive malignant HRS cells. Intriguingly, an increased number of tumor-associated macrophages (TAM) was strongly associated with treatment failure and shortened survival in patients with cHL. TAM can express PD-1 and this suggests that anti-PD-1 therapies may also function through a direct effect on macrophages. Left untreated, the prognosis of HLH is poor and generally fatal. Therefore, prompt recognition and timely treatment are critical. Usually, in patients who present with secondary HLH, treatment of the underlying cause can lead to control and resolution of HLH. At the onset of HLH, our patient had a chemorefractory cHL and conventional treatment of HLH was totally ineffective. The anti-PD1 antibody nivolumab induce a high overall response rate in relapsed/refractory cHL. In our patient nivolumab induced a prompt control of HLH and a subsequent complete remission of cHL. More knowledge is warranted about interactions between macrophages and PD-1/PDL-1 inhibitors.
Session topic: 17. Hodgkin lymphoma – Clinical
Abstract: PB2021
Type: Publication Only
Background
Hemophagocytic lymphohistiocytosis (HLH) is an infrequent but potentially life-threatening hyperinflammatory syndrome that occurs in about 6% of patients affected by Hodgkin Lymphoma. Treatment of secondary HLH includes corticosteroids, cyclosporine A, etoposide and/ or malignancy-directed therapies. Anecdotal cases report successful results with Alemtuzumab, Infliximab, Daclizumab, Blinatumomab and Ruxolitinib.
Aims
We describe a case of HLH complicating refractory classical Hodgkin lymphoma (cHL) that resolved only after treatment with Nivolumab. At our knowledge, this is the first case reported.
Methods
A 21-year-old man was diagnosed with cHL, CS IIIB, in September 2014. He was refractory to five lines of treatment (ABVD, IGEV, Brentuximab Vedotin, Bendamustine and Beacopp). In April 2016 he developed fever, marked splenomegaly and grade 4 pancytopenia. Other laboratory findings showed hypoalbuminemia, hypertransaminasemia and hyperbilirubinemia; antibody tests for HCV, HBV, HIV, HSV, CMV and EBV infections were negative. The bone marrow biopsy showed the presence of numerous macrophages embedding hematopoietic elements, without lymphoma infiltration. Consequently, HLH was diagnosed. Treatment with corticosteroids and etoposide was ineffective. In May 2016 he started treatment with Nivolumab (in the setting of the Italian Extented Access Program) at the dose of 3 mg/kg every 14 days.
Results
Until Nivolumab treatment was started the patient required transfusion support with 14 PRBC Units and 19 Plt Units. After the first administration of Nivolumab he developed an episode of respiratory insufficiency infusion related that resolved with mild corticosteroid therapy. The patient became transfusion independent after the third dose of Nivolumab. After 32 doses of Nivolumab, in November 2017 treatment was stopped because of a severe pancreatitis treatment related. Unfortunately in February 2018 the patient died in complete remission in a road accident.
Conclusion
HLH is a potentially fatal hyperinflammatory disease induced by a pathologic immune activation, with proliferation of well-differentiated macrophages/histiocytes and increased phagocytic activity. The tumor in cHL is mainly composed of inflammatory cells providing a protective niche to the sparse CD30-positive malignant HRS cells. Intriguingly, an increased number of tumor-associated macrophages (TAM) was strongly associated with treatment failure and shortened survival in patients with cHL. TAM can express PD-1 and this suggests that anti-PD-1 therapies may also function through a direct effect on macrophages. Left untreated, the prognosis of HLH is poor and generally fatal. Therefore, prompt recognition and timely treatment are critical. Usually, in patients who present with secondary HLH, treatment of the underlying cause can lead to control and resolution of HLH. At the onset of HLH, our patient had a chemorefractory cHL and conventional treatment of HLH was totally ineffective. The anti-PD1 antibody nivolumab induce a high overall response rate in relapsed/refractory cHL. In our patient nivolumab induced a prompt control of HLH and a subsequent complete remission of cHL. More knowledge is warranted about interactions between macrophages and PD-1/PDL-1 inhibitors.
Session topic: 17. Hodgkin lymphoma – Clinical