CTLA4 blockade with ipilimumab to treat relapse of malignancy after allogeneic hematopoietic cell transplantation

Abstract

Relapse of malignancy after allogeneic hematopoietic cell transplantation (allo-HCT

The emerging role of immune checkpoint inhibition in malignant lymphoma

“…A single dose of ipilimumab in patients who relapsed after allogeneic SCT appeared to be safe with no case of severe GvHD reported among 29 patients. 30 A French study of nivolumab in r/r cHL after allogeneic SCT reported limited toxicity and no cases of significant GvHD, 35 which is in contrast to preliminary results of an ongoing trial of ipilimumab in relapsed malignancies after allogeneic SCT reported at ASH 2015. 83 This trial included 28 patients, five of whom had drugrelated toxicities leading to treatment discontinuation, including three cases of grade 3 chronic liver GvHD and one case of acute intestinal GvHD.…”

“…30 On the other hand, preliminary results of an ongoing phase II trial of pembrolizumab in r/r CLL patients, including those with Richter syndrome, showed an ORR of 21% in 20 evaluable patients. Responses, including one CR, were documented in three patients with Richter syndrome and also in patients in whom prior ibrutinib therapy had failed.…”

“…In contrast, a PR was observed in a single MCL patient treated with ipilimumab for relapse after allogeneic SCT. 30 Four MCL patients treated with nivolumab did not respond. 47 Results of currently ongoing combination trials with nivolumab and ipilimumab or anti-KIR therapy are pending (Table 2).…”

“…The drug was well tolerated, with no cases of relevant graft-versus-host disease (GvHD) and two patients achieved a complete remission (CR). 30 Preliminary results of a NCI-sponsored phase I/II trial testing 3 mg/kg ipilimumab in combination with 1.8 mg/kg BV in r/r cHL showed an overall response rate (ORR) of 72% with a 50% CR rate in 18 evaluable patients. 31 More recently, two early phase trials with anti-PD1 antibodies in r/r HL patients reported encouraging results: the dose-escalation phase I trial of nivolumab included 23 intensively pretreated r/r cHL patients and the ORR was 87%.…”

Ipilimumab Associated Autoimmune Alveolitis Responding to Corticosteroids

“…In Phase II studies less than 1 in 100 treated patients developed Grade 3 or 4 cough, dyspnea or pleural effusion [15]. There is only one previous report of autoimmune pulmonary toxicity related to ipilimumab administration [16]. The adverse pulmonary events, dyspnea and pneumonitis, occurred in patients treated with ipilimumab who had relapsed haematologic malignancies after allogeneic haematopoetic stem cell transplantation.…”