Real-world retrospective analysis of immune checkpoint inhibitor therapy for relapsed or refractory Hodgkin's lymphoma

Abstract

Immune checkpoint inhibitors (ICI) are promising therapeutic agents for relapsed or refractory classical Hodgkin's lymphoma (RRcHL). This retrospective study evaluated patients with RRcHL registered in the clinical research program Tohoku-Hematology-Forum-26, between 2016 and 2020, and treated with ICI in 14 centers in Northeast Japan. We analyzed the usage, efficacy, and safety of ICI therapy (ICIT). Among a total of 27 patients with RRcHL, 21 and nine were treated with nivolumab and/or pembrolizumab, respectively. The best response was complete response (CR), partial response (PR), stable disease (SD), and progressive disease in 11 (40.8%), seven (25.9%), eight (29.6%), and one (3.7%) patient, respectively. In all patients undergoing ICIT, the 2-year progression-free survival and 2-year overall survival (OS) were 48.6% and 87.4%, respectively. The 2-year OS for patients with CR, PR, and SD were 100%, 68.6%, and 87.5%, respectively. A total of 36 events of immune-related adverse events (irAEs) or immune-related like adverse events (irlAEs) were observed in 19 of the 27 patients (70.4%). Two thirds of these irAEs or irlAEs were grade 1-2 and controllable. During the observation period, ICIT was discontinued in 22 of 27 (81.4%) patients due to CR, inadequate response, irAE and patient circumstances in five (22.7%), seven (31.8%), eight (36.4%) and two patients (9.1%), respectively. Therapy-related mortality-associated irAE were observed in only one patient during ICIT. These results suggest that ICIT for RRcHL is effective and safe in real-world settings. The optimal timing of induction and duration of ICIT remains to be established.

Keywords: classical Hodgkin’s lymphoma; immune checkpoint inhibitors; real-world setting; relapsing and refractory cHL.

Fig. 1

Treatment exposure and duration of response among 27 patients with initial or second immune checkpoint inhibitor therapy (ICIT). CBSCT, cord blood stem cell transplantation; DeVIC, dexamethasone etoposide ifomide carboplatin; BV, brentuximab vedotin; related-PBSCT, related peripheral blood stem cell transplantation; c-MOPP, cyclophosphamide mechlorethamine vincristine procarbazine prednisolone; MEAM, ranimustine etoposide cytarabine melphalan; Auto-PBSCT, auto-peripheral blood stem cell transplantation; DHAP, dexamethasone high-dose cytarabine cisplatin; MCVC, ranimustine carboplatin etoposide cyclophosphamide; BEACOPP, bleomycin etoposide doxorubicin cyclophosphamide vincristine procarbazine prednisolone; PEPC, prednisolone, etoposide, procarbazine, cyclophosphamide; CHASE, cyclophosphamide cytarabine etoposide dexamethasone; chronic GVHD, chronic graft versus host disease; PD, progression disease; ICIT, immune checkpoint inhibitor therapy; irAE, immune-related adverse event.

Fig. 2

Kaplan–Meier plots of progression-free survival (PFS) over a median follow-up duration of 439 (57–1477) days.

Fig. 3

Kaplan–Meier plots of overall survival (OS) over a median follow-up duration of 635 (57–1722) days.

Fig. 4

Kaplan–Meier plots of progression-free survival (PFS) according to the best overall response (BOR) over a median follow-up duration of 439 (57–1477) days.

Fig. 5

Kaplan–Meier plots of overall survival (OS) according to the best overall response (BOR) over a median follow-up duration of 635 (57–1722) days.