Sintilimab Plus Gemcitabine, Cisplatin, and Dexamethasone As Second-Line Therapy for Relapsed or Refractory Classical Hodgkin Lymphoma：a Multicenter Retrospective Study

Background: Classical Hodgkin lymphoma (cHL) is highly curable by frontline therapy. However, the search for an effective standard second-line therapy for patients with refractory or relapsed (R/R) cHL continues. Sintilimab, a fully human IgG4 monoclonal antibody targeting the PD-1 receptor, has demonstrated significant efficacy in R/R cHL. This study evaluates the efficacy of sintilimab combined with gemcitabine, cisplatin, and dexamethasone (S-GDP), an economical regimen cost only 600 dollars per cycle, as second-line therapy for R/R cHL.

Methods: We conducted a retrospective study including 24 patients with R/R cHL who received S-GDP (gemcitabine, 800 mg/m², d1,8; cisplatin, 25 mg/m², d1-3; dexamethasone, 20mg bid, d1-4; sintilimab, 200mg, d8; 21 days/cycle) as second-line therapy from March 2020 to January 2024. After the combination treatment, patients could receive ASCT or RT as consolidation therapy, followed by sintilimab maintenance. The primary endpoint was the best overall response rate (ORR) during the second-line therapy according to the 2014 version of Lugano efficacy evaluation criteria, and the secondary endpoints included complete response (CR), partial response (PR), progression-free survival (PFS), and adverse events (AEs).

Results: Twenty-four patients (15 males; median age 34 years, range, 17-55) from 4 institutions with histologically confirmed cHL were included in this retrospective study, of whom 18 patients were Ⅲ-Ⅳ stage, 13 patients were refractory. Fourteen advanced-stage patients (77.8%) had International Prognostic Score (IPS) scores≥3. Six early-stage patients (100%) had unfavorable factors. The median number of treatment cycles was 6 (range 1-8). The ORR and CRR were 83.3% and 62.5%, respectively. In refractory patients, the ORR and CRR were 76.9% and 61.5%, respectively, while in relapsed patients, the ORR and CRR were 90.9% and 63.6%, respectively. With a median follow-up of 45.2 months, the median PFS was 42.5 months for all patients, 45.2 months for refractory patients, 34.2 months for relapsed patients. Among the 24 patients, 11 patients received ASCT with subsequent sintilimab maintenance, 3 patients rejected ASCT as consolidation therapy with only sintilimab maintenance, 1 patient received only RT as consolidation therapy. The most common AEs were leukopenia (91.6%) and anemia (83.3%), with grade 3-4 AEs including leukopenia (20.8%), thrombocytopenia (8.3%), and pneumonia (8.3%). No treatment-related severe AEs or mortality occurred.

Conclusion: The S-GDP regimen is an effective, economical, and well-tolerated second-line therapy for R/R cHL, efficiently bridging patients to ASCT and offering a promising alternative for this patient population.

No relevant conflicts of interest to declare.

Sintilimab was approved in China for the treatment of classical Hodgkin's lymphoma in patients who have relapsed or are refractory after ≥ 2 lines of systemic chemotherapy. However, sintilimab was recommended for the treatment of relapsed or refractory classical hodgkin lymphoma by CSCO Guidelines. Besides, pembrolizumab (drug of the same class) was used as second-line therapy for relapsed or refractory classical hodgkin lymphoma recommended by NCCN Guidelines.