The combination of camrelizumab plus gemcitabine, vinorelbine, and pegylated liposomal doxorubicin demonstrated promising efficacy in patients with relapsed/refractory primary mediastinal B-cell lymphoma. The combination also had a manageable safety profile, according to findings from a phase 2 clinical trial.
The combination of camrelizumab (AiRuiKa, SHR-1210) plus gemcitabine, vinorelbine, and pegylated liposomal doxorubicin (GVD) demonstrated promising efficacy in patients with relapsed/refractory (R/R) primary mediastinal B-cell lymphoma (PMBCL). The combination also had a manageable safety profile, according to findings from a phase 2 clinical trial.
This open-label, single-arm, study was conducted due to the limited treatment options for R/R PMBCL, which is a disease associated with poor prognosis. The treatment options that are available for the disease include salvage therapies, high-dose chemotherapy, and autologous stem cell transplant (ASCT),but none of these are considered optimal as response rates observed with these treatments are low. However, there are prior data showing the potential efficacy and tolerability of GVD in patients with PMBCL, in addition to those with diffuse large B-cell lymphoma and classical Hodgkin lymphoma (cHL). Additionally, camrelizumab as a monoclonal antibody demonstrated favorable results were evaluated in patients with R/R cHL. This prior finding hinted that camrelizumab may also be beneficial for patients with R/R PMBCL. Investigators led by Weidong Han, PhD, MD, therefore set up to explore both therapies combined with objective response rate (ORR) as the primary end point.
The patient population in this study had a median age of 30 years (range, 18-45 years), and 52% of them were female. The majority of patients had advanced bulky disease (59%), which was defined as having a tumor ≥7.5 cm. Also, 81% of patients (n = 22), had elevated lactate dehydrogenase, and 52% (n = 14) had stage IV disease. For 63% of patients (n = 17), receipt of camrelizumab plus GVD occurred in the fourth-line setting or later. Of the individuals who received prior rituximab (Rituxan)-containing regimens, the median cycle was 7 (range, 2-11). There were also 24 patients (89%) with primary refractory disease.
Most patients in the study were transplant ineligible due to their resistance to chemotherapy. In terms of other prior treatments, 70% of patients (n = 19) had dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R), 37% (n = 19) had prior radiotherapy,7% (n = 2) underwent previous ASCT, and 11% (n = 3) had prior chimeric antigen receptor (CAR) T-cell therapy.
The total number of patients evaluable for response was 27. At a median follow-up of 24.8 months (range, 3.2-32.4), the ORR was 74.1% (95% CI, 55.3-86.8), with complete responses (CRs) observed in 55.6% of patients (95% CI, 37.3-72.4). Han et al observed that females had a better ORR than males (P =.033). It was also observed that receipt of camrelizumab plus GVD in earlier settings resulted in better responses (P =.0026). Having bulky disease seemed to correlate with CR in patients (P =.0005), but it had no association with objective response (P =183). higher PD-L1 expression trended toward more frequent CRs (P =.056). Notably, there was 1 patient in the study whose partial response upgraded to a CR during maintenance therapy.
The time to first objective response took a median of 1.7 months (95% CI, 1.6-1.8). Decreases in target lesions were seen in 27 patients (77.8%, [95% CI, 59.2%-89.4%]) at the first CT scan. Across subgroups of patients, the median time to treatment response appeared similar but was notably shorter for patients who did not have prior radiotherapy, compared with other subgroups of patients (P =.006).
The median duration of response (DOR) was not reached (NR) in this study (95% CI, 8.6 to NR). Seventy percent (95% CI, 45.1-85.3) of patients had a response lasting greater than 12 months. Remissions were sustained for 17 to 30 months in 86.7% (n = 15) of the complete responders in the study.
In terms of survival, estimates were calculated for 12-month and 24-month progression-free survival (PFS), which was 55.6% (95% CI, 35.2%-71.8%) for 12 months and 48.2 (95% CI, 28.7%-65.2%) for 24 months. The median PFS was 15.4 months (95% CI, 4.6 to NR).
The median overall survival (OS) was also NR, but the estimated 2-year OS rate was 81.5% (95% CI, 61.1%-91.8%). Of note, survival outcomes in male patients with bulky disease were found to be associated with PFS, according to a post-hoc exploratory analysis.
Ninety-three percent of patients in the study (n = 25) experienced treatment-related adverse events (AEs), and of those treatment-related AEs, 33% (n = 9) of them were grade 3 in severity. However, no grade 4 or 5 events were reported. Of the grade 3 AEs, the most frequently reported included neutropenia (19%), and leukocytopenia (19%). There was also 1 patient who had grade 1 capillary hemangioma. Some of the grade 1 and 2 AEs were considered to be chemotherapy-related but were well tolerated in patients. Grade 3 events were able to be resolved with supportive care.
AEs caused by immunotherapy were seen in 56% of patients (n = 15). Pruritus, occurring in 30% of patients, was the most common immunotherapy-related AE. Overall, these toxicities were well tolerated and did not delay therapy. Two patients who had immunotherapy-related AEs discontinued treatment due to grade 2 and grade 3 pneumonitis.
A total of 9 patients discontinued study treatment but remained in the 24.8-month follow-up. Five of those patients died as a result of disease progression.
The study population consisted of adult patients aged 18 years or older with R/R PMBCL confirmed centrally of pathologically. All subjects were required to have at least 1 mediastinal mass which could be no large than 5 cm in diameter, with or without extrathoracic disease. In addition, patients were required to have an ECOG performance status of 0 to 2 with adequate organ function.
During the study, patients received gemcitabine 1000 mg/m2, vinorelbine 30 mg, and pegylated liposomal doxorubicin 20 mg/m2 combined with 200 mg camrelizumab 200 mg, which was administered on day 2, every 3 weeks. All study treatments were continued until disease progression, unacceptable toxicity, or withdrawal of patient consent. The study included a maintenance phase of camrelizumab 200 mg, given intravenously every 3 weeks for 4 cycles, then every 6 weeks, for a maximum of 1 year.
Based on the data from this study, Han et al recommend the use of camrelizumab plus GVD for patients with bulky aggressive R/R PMBCL. Concerning the cohort of younger patients, the investigators plan to continue to assess the DOR in these patients.
Mei Q, Zhang W, Liu Y, et al. Camrelizumab plus gemcitabine, vinorelbine and pegylated liposomal doxorubicin in relapsed/refractory primary mediastinal B-cell lymphoma: a single-arm, open-label, phase 2 trial. Clin Cancer Res. Published Online First on June 4, 2020. doi:10.1158/1078-0432.CCR-20-0514