Hematopoietic stem cell mobilization following PD‐1 blockade: Cytokine release syndrome after transplantation managed with ascorbic acid

Abstract

Patients with recurrent/refractory (R/R) classical Hodgkin's Lymphoma (cHL) have poor survival with conventional therapy.In these patients, autologous hematopoietic stem cell transplant (SCT) is the most commonly employed salvage therapy. 1 Immune checkpoint inhibitors also have significant activity in recurrent HL. 2 Program death-1 (PD-1) is a crucial pathway in immune tolerance. Nivolumab is a PD-1 antagonist that was the first approved checkpoint inhibitor in hematological malignancies including HL.PD-1 blockade leads to the activation of T cells breaking immune tolerance. Nivolumab has an emerging role in the management of patients who have relapsed after autologous transplant. 2 However, the safety of novel PD-1 inhibitors administered before autologous transplantation is unknown. We report here a patient who received nivolumab prior to autologous stem cell mobilization and transplantation who subsequently developed cytokine storm. This was successfully managed using parenteral ascorbic acid. | C A S E REP ORTA 28-year-old female patient was diagnosed with cHL stage IV, mixed cellularity subtype. She underwent four cycles of frontline chemotherapy with adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD). On follow-up imaging, she showed disease progression. She then received three cycles of ifosfamide, carboplatin, and etoposide, followed by a single cycle of brentuximab, and complicated by pancreatitis. A single 240 mg dose of nivolumab was administered 26 days prior to stem cell mobilization and collection. Stem cells were mobilized using filgrastim 10 μg/kg/d for 4 days. Conditioning regimen for stem cell transplant (SCT) was carmustine, etoposide, cytarabine, and melphalan (BEAM), followed by an infusion of 4.1 × 10 6 CD34 + cells/kg on day 0. On day +1 post-SCT, she became febrile. Cefepime and vancomycin were initiated for febrile neutropenia. Chest imaging revealed mild basilar volume loss. On day +3, she developed diarrhea and was diagnosed with Clostridium difficile infection. Oral vancomycin was initiated. Day Abstract Checkpoint inhibitor therapy is effective in the treatment of relapsed classical Hodgkin's Lymphoma. Here, we report a patient with relapsed Hodgkin's Lymphoma who received nivolumab prior to autologous stem cell mobilization. She went on to develop cytokine storm shortly following transplantation, with marked T-cell proliferation coincident with myeloid engraftment. Non-cardiogenic pulmonary edema and alveolar hemorrhage developed despite corticosteroid therapy. There was rapid and complete resolution of these complications with parenteral ascorbic acid infusion. Our case illustrates the risk of cytokine release syndrome following infusion of stem cells mobilized after checkpoint inhibitor therapy and the role of ascorbic acid in its management. K E Y W O R D S bone marrow transplantation, Hodgkin's lymphoma, transplantation

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