The 28th European Hematology Association (EHA) Congress took place from June 8 to 11, 2023, in Frankfurt, Germany, organized by the European Hematology Society. As one of the largest international conferences in the field of hematology globally, the EHA Congress gathered top hematologists worldwide, covering various aspects of hematologic research, including oral presentations, poster presentations, and more. In this edition of Oncology Frontier, we focus on key clinical research in Hodgkin lymphoma presented in the oral presentation sessions, aiming to provide a quick overview of the latest advancements in this field.
01 CD47/PD-L1 Bispecific Antibody (IBI322) Treatment for PD-1 or PD-L1 Resistant Classical Hodgkin Lymphoma (cHL): Efficacy and Safety in Phase I Study
Abstract Number: S216
Presenting Expert: Yu Jingwei, Tianjin Medical University Cancer Institute and Hospital, China
The disclosed data are based on an extension cohort of a Phase I clinical trial (ClinicalTrials.gov registration number: NCT04795128), primarily assessing the safety and preliminary anti-tumor activity of IBI322 in patients with classic Hodgkin lymphoma resistant to anti-PD-(L)1 monoclonal antibody treatment. Eligible patients received IBI322 (45 mg/kg intravenous infusion every two weeks) until unacceptable toxicity, disease progression, or a maximum of 24 months. A total of 24 subjects were enrolled, with 23 evaluable for efficacy.
Results showed that among the 23 patients, the objective response rate (ORR) and disease control rate (DCR) were 47.8% (95% CI: 26.8-69.4) and 91.3% (95% CI: 72.0-98.9), respectively. In 7 primary resistant patients, the ORR was as high as 57.1% (95% CI: 18.4-90.1), with 3 achieving complete response (CR).
Regarding safety, the treatment-related adverse event (TRAE) incidence was 91.7%, with the most common TRAEs being lymphocyte count decrease (62.5%), anemia (62.5%), white blood cell count decrease (20.8%), and platelet count decrease (20.8%). The incidence of ≥3 grade TRAEs was 41.7%, with lymphocyte count decrease being the most common (29.2%). No TRAEs led to permanent discontinuation or death. As of data cutoff, 12 patients were still receiving IBI322 monotherapy.
These results indicate promising anti-tumor activity and manageable safety of IBI322 monotherapy in patients with classic Hodgkin lymphoma resistant to anti-PD-1 or PD-L1 treatment.
02 Post-Transplant Nivolumab Combined with Unselected Autologous Lymphocytes Achieves High Remission Rates and Excellent Survival in Patients with Refractory Hodgkin Lymphoma, Correlated with NK Cell Expansion
Abstract Number: S217
Presenting Expert: Dr. Fabio Guolo, University of Genoa, Clinic of Hematology, Department of Internal Medicine (DiMI), Genova, Italy
To improve the efficacy of immune checkpoint inhibitors (CI) in treating refractory Hodgkin lymphoma (RHL) patients, this study utilized early autologous stem cell transplantation (ASCT) followed by CI (nivolumab) treatment, reinfusion of unselected autologous lymphocytes (ALI), and assessed the efficacy based on complete response rate (CR) and overall survival (OS). The biological endpoint aimed to study lymphocyte subpopulations involved in the response mechanism.
The study included 21 RHL patients categorized into treatment group (n=13, those who failed second and third-line treatments) and control group (n=8, patients responsive to second-line chemotherapy or third-line brentuximab vedotin (BV)). The treatment group received early post-transplant CI and support with 4 ALI infusions, while the control group received ASCT followed by ALI alone.
Results indicated that all patients in the treatment group were disease-free at a median follow-up of 32 months (95% CI: 26.4-51.0). In the control group, 4 patients experienced relapse (50%). The treatment group did not reach median disease-free survival (DFS), while the control group’s median DFS was 22 months. Phenotypic analysis of circulating cells showed a faster expansion of highly differentiated NK cells in the ALI+CI treatment group compared to the control group.
The study results suggest a highly potent anti-tumor activity of ALI+CI in treating RHL. The outcomes for RHL patients in the treatment group were favorable compared to the control group, including patients responsive to conventional treatments. Biological data indicate that this approach may accelerate the development/maturity of NK cells and contribute to the expansion of the “adaptive” NK cell compartment.
03 Pembrolizumab Used in Newly Diagnosed Children and Young Adults with cHL Insensitive to First-Line Chemotherapy: Phase II, Open-Label, KEYNOTE-667 Study
Abstract Number: S215
Presenting Expert: IRCCS Ospedale Pediatrico Bambino Gesu, Rome, Italy
The presented data are from the mid-term analysis of the KEYNOTE-667 study (ClinicalTrials.gov registration number: NCT03407144). The study aimed to evaluate the efficacy and safety of pembrolizumab combined with chemotherapy in treating early slow-responding (SER) classical Hodgkin lymphoma (cHL) patients. Forty-nine high-risk cHL patients with SER received pembrolizumab consolidation therapy in addition to four cycles of cyclophosphamide, vincristine, prednisone/prednisolone, dacarbazine (COPDAC-28).
Results showed that, at data cutoff with a median follow-up of 15.3 months (3.2-30.5), 22 patients (45%) completed treatment, 24 patients (49%) were undergoing consolidation or maintenance, with a median treatment duration of 10.4 months (0.5-11.8). Forty-two patients (86%) underwent delayed response assessment (LRA), and 27 patients (64%) were PET-negative according to BICR evaluation.
Regarding safety, 42 patients (86%) experienced any adverse events (AE), 30 patients (61%) had treatment-related adverse events (TRAE). Six patients (12%) experienced grade 3/4 TRAEs. Four patients (8%) had immune-mediated hypothyroidism AE.
These results suggest that pembrolizumab combined with COPDAC-28 treatment for first-line
chemotherapy-insensitive high-risk cHL patients has manageable safety and promising anti-tumor activity. Adding pembrolizumab to COPDAC-28 may enhance the response in high-risk cHL populations.
TAG: EHA 2023, Review，Hematological Malignancy, Hodgkin Lymphoma
