Tolerance and effectiveness of nivolumab after pediatric T‐cell replete, haploidentical, bone marrow transplantation: A case report

Abstract

To date, there has been a lack of pediatric experience regarding the efficacy and tolerability of immune checkpoint inhibitors after haploidentical hematopoietic stem cell transplant (HSCT). We present the case of a 22-year-old female with multiple-relapsed Hodgkin lymphoma (HL) who presented with a new relapse after haploidentical (post-haplo) HSCT. Anti-PD-1 therapy with nivolumab resulted in significant objective disease response and clinical improvement without notable side effects, including the absence of a graft-versus-host disease (GVHD). This case report suggests that immune checkpoint inhibition may be safely tolerated even in the setting of haploidentical HSCT, without triggering overt GVHD.

Significant Risk of Graft-versus-Host Disease with Exposure to Checkpoint Inhibitors before and after Allogeneic Transplantation

“…The other fourteen patients (54%) were treated with nivolumab (PD-1 blockade), two with a single infusion at 3 mg/kg (27), two patients with six and four cycles (dose not mentioned) respectively (26). Two patients received a single dose of 100 mg (25) and 200 mg (24), two were treated with a single 3 mg/kg dose, one with two doses of 100 mg (25) two weeks apart, two cases with thirteen (23) and sixteen (20) cycles of 3 mg/kg every two weeks, one case with seven cycles of 2 mg/kg every two weeks (16), two cases with seven (19) and sixteen cycles (16) of 2 mg/kg every three weeks respectively. One case treated with five weekly doses of 0.3–1.0 mg/kg (25) and two patients with an escalating dosage of 0.5 to 3 mg/kg (15) and 0.5 to 2.0 mg/kg(18) for up to six doses.…”

Limitations and opportunities for immune checkpoint inhibitors in pediatric malignancies

“…Blumenthal et al reported their experience of pembrolizumab in patients with recurrent brain tumors including 5 pediatric patients, but they failed to show a benefit on overall survival [39]. The obvious exceptions are pediatric patients with refractory Hodgkin lymphoma (HL) which have shown durable responses to pembrolizumab [40,41]. Recently, pembrolizumab was approved by FDA for HL in adult and pediatric patients, and this is a first approval of PD-1 inhibitor for pediatric use.…”

“…Although clinical trials have shown tumor responses in some patients, few are major responses and most have not been durable [12,39–41]. There is a need to better understand the mechanisms of action of PD-1/PD-L1 in these pediatric tumors, to determine if there is an underlying genetic resistance to ICIs [13,96].…”

Immune checkpoint inhibitors in challenging populations

“…Anti‐PD1/PD‐L1 has also been used safely in several patients after hematopoietic stem cell transplantation . However, several cases of renal and cardiac allograft rejection and serious GVHD have also been reported soon after the initiation of anti‐PD1 in patients with various advanced malignancies .…”

“…[16][17][18][19][20][21] Anti-PD1/PD-L1 has also been used safely in several patients after hematopoietic stem cell transplantation. 16,[22][23][24][25][26] However, several cases of renal and cardiac allograft rejection and serious GVHD have also been reported soon after the initiation of anti-PD1 in patients with various advanced malignancies. 17,[27][28][29][30][31][32][33] In particular, on the basis of these published case reports, renal transplant patients seem to be at high risk for rejection.…”