**Table 1.**

*Overview of clinical efficiency and toxicity results of PD-1 inhibitors, nivolumab and pembrolizumab, in Hodgkin's lymphoma.*

#### *Immune Checkpoint Inhibitors - New Insights and Recent Progress*

*Immune Checkpoint Inhibitors in Hodgkin Lymphoma and Non-Hodgkin Lymphoma DOI: http://dx.doi.org/10.5772/intechopen.107435*

#### *2.1.1.2 Other combined therapy*

The regimen AVD regimen (doxorubicin, vinblastine, and dacarbazine) is the backbone of the well-established chemotherapy regimen ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) for HL [65]. Therefore, the efficacy of nivolumab and AVD combination in early-stage cHL was assessed [66]. In total, 109 patients were given two different treatment strategies (of dosing and sequencing), and both groups displayed promising outcomes, with over 90% CR and nearly 100% 12-month PFS. Another multicenter, single-arm, phase II trial proved that pembrolizumab followed by AVD was both effective and safe in patients with untreated early unfavorable and advanced-stage cHL, with all patients (*n* = 30) achieving complete metabolic response (CMR) [67]. At the median follow-up of 22.5 months, the PFS and OS are 100%, indicating the superior efficacy of the strategy.

Brentuximab vedotin (BV) is a CD30-based antibody-drug conjugate. When used alone, it can lead to an ORR of 72% and CR rate of 33% in r/r HL patients [68]. Advani et al. [69] reported that BV combined with nivolumab can be the first salvage therapy in patients with r/r cHL, with an ORR of 85% and CR rate of 67%. In a median follow-up of 34.3 months, the estimated 3-year PFS and OS were 77% and 93%, respectively. Such combination treatment can be applied as a first-line option for older or chemotherapy-ineligible cHL patients, as demonstrated by Cheson et al. [70]. With a total of 46 patients and a median follow-up of 21.2 months, 48% of patients achieved CR and 13% achieved PR, with an ORR of 61%. Due to the high efficacy of this combination, it was considered as a salvage option after PD-1 blockade failure. In 21 r/r cHL patients who failed nivolumab monotherapy previously, BV combined with nivolumab resulted in an ORR of 57% [71]. Twenty-four-month PFS and OS were 31% and 80%, respectively. In total, 63% of patients suffered from adverse effects (AEs), but AEs of grade 3 or 4 were only observed in 10% of patients.

The potential synergistic effect of radiotherapy and ICIs has been proposed as well. In a cohort of 12 patients with r/r cHL, patients were given a combined treatment of radiotherapy and nivolumab/pembrolizumab, with an ORR of 100% and a CR rate of 58% [72]. With a median follow-up of 18 months, 92% of patients remained in CR (9 of 12 patients underwent HSCT consolidation). Forceville et al. [73] presented two case reports supporting that radiotherapy combined with nivolumab can lead to excellent outcomes.

Gemcitabine, vinorelbine, and liposomal doxorubicin (GVD) are traditional second-line treatment options for r/r cHL, with a CR rate of around 50% [74]. In comparison, the combination of GVD and pembrolizumab resulted in an ORR of 100% and a CR rate of 95%, with a total of 39 enrolled r/r cHL patients [75]. In total, 36 of these 39 patients underwent subsequent auto-HSCT, and they all remained in CR at a median post-transplant follow-up of 13.5 months. In a similar trial consisting of 103 patients (27 for GVD + PD-1 blockade, 76 for GVD), the combination group had a higher CR rate of 85.2% (65.8% for the GVD group) and an extended PFS (1-year PFS of 82.2% vs. 67.9% for GVD group) [76].

#### *2.1.2 Camrelizumab*

Camrelizumab (SHR-1210), which was developed in China, is a humanized high-affinity anti-PD-1 IgG4 monoclonal antibody. It has shown promising efficacy against numerous advanced solid tumors including nasopharyngeal carcinoma, esophageal carcinoma, gastric and gastroesophageal junction cancer [77–81]. In a

single-arm, multicenter, phase II study (NCT03155425), a total of 75 patients with r/r cHL were given Camrelizumab 200 mg every 2 weeks intravenously. In a median follow-up of 12.9 months, 21 (28.0%) and 36 (48.0%) patients achieved complete or partial remission, respectively (i.e., objective response rate is 76.0%). Treatmentrelated adverse events (AE) were observed in all patients enrolled, with 20 (26.7%) of them exhibiting grade 3 or 4 treatment-related AEs [82]. The group further extended the follow-up of this clinical trial till 2020, with a median follow-up duration of 36.2 months. The objective response rate remained almost unchanged. The median PFS was 22.5 months and 3-year OS was 82.7%.
