The 29th European Hematology Association (EHA) Annual Meeting took place from June 13-16, 2024, in Madrid, Spain. As Europe's largest international event in the field of hematology, the meeting attracts numerous renowned experts and scholars worldwide to share and discuss innovative ideas, the latest scientific research, and clinical research outcomes in hematology. At this year's conference, multiple research findings from Professor Jie Jin's team at The First Affiliated Hospital, Zhejiang University School of Medicine were selected. To gain a deeper understanding of the latest research in relapsed/refractory multiple myeloma (RRMM) (P961), "Oncology Frontier - Hematology Frontier" invited Professor Jie Jin for an in-depth discussion.Oncology Frontier – Hematology Frontier: At this conference, several of your team’s studies were selected. Among them, P961 is about GR1803 (a BCMA×CD3 bispecific antibody) monotherapy for relapsed/refractory multiple myeloma. Could you introduce the background and main results of this study?
Professor Jie Jin: Currently, the prognosis for patients with relapsed/refractory multiple myeloma (RRMM) remains poor. GR1803 is a bispecific antibody that can simultaneously bind to the BCMA and CD3 antigens, redirecting cytotoxic T cells to target BCMA-expressing myeloma cells. Its affinity for BCMA (10^-10 M) is two orders of magnitude higher than for CD3 (10^-8 M), ensuring that the bispecific antibody recruits and activates T cells to kill tumor cells while minimizing non-specific T cell activation and reducing the toxicity mediated by the CD3 antibody.
This phase I clinical study aimed to evaluate the safety, pharmacokinetics, immunogenicity, and preliminary efficacy of GR1803 injection in patients with RRMM. Patients previously treated with proteasome inhibitors, immunomodulators, and CD38 monoclonal antibodies received weekly intravenous injections of GR1803 for 24 weeks. As of January 30, 2024, the dose-escalation study and dose-expansion study for two dose groups (180 μg/kg and 240 μg/kg) were completed. By January 18, 2024, a total of 50 patients had been enrolled, with 16 in the dose-escalation study and 34 in the dose-expansion study.
As of January 31, 2024, 40 patients had completed at least one efficacy evaluation. The overall objective response rate (ORR) for the 40 evaluable patients was 85% (34/40), with most responding patients continuing treatment, and the longest follow-up being 44 weeks. In the 180 μg/kg dose group, 25 patients were enrolled, with a median follow-up of 15 weeks (range: 3-32 weeks). Among the 23 patients who completed at least one efficacy evaluation, the ORR was 96% (22/23), with a very good partial response (VGPR) or better rate of 43% and a complete response (CR) or better rate of 13%. For the 13 patients with baseline extramedullary multiple myeloma (EMM) in the 180 μg/kg dose group, the median follow-up was 20 weeks (range: 10-25 weeks), with an ORR of 100% (13/13), including 7 VGPR and 6 PR.
Most patients achieved PR or better at the first efficacy evaluation, with a median time to response of 3 weeks. The responses were durable and improved with continued treatment. The median progression-free survival (mPFS) and median duration of response (mDOR) were not reached, and no disease progression occurred in any responding patients.
In terms of safety, 49 patients (98%) experienced at least one treatment-related adverse event (TEAE), and 48 patients (96%) had grade 3 or higher TEAEs. Common TEAEs (≥20%) included infections (70%, with 38% grade ≥3), cytokine release syndrome (80%, with 6% grade ≥3), fever (40%, with 4% grade ≥3), anemia (70%, with 32% grade ≥3), neutropenia (76%, with 50% grade ≥3), thrombocytopenia (64%, with 48% grade ≥3), leukopenia (66%, with 32% grade ≥3), lymphopenia (62%, with 60% grade ≥3), hypokalemia (52%, with 16% grade ≥3), and diarrhea (38%, with 8% grade ≥3). Two patients in the 360 μg/kg dose cohort had dose-limiting toxicities (DLTs).
Overall, GR1803 monotherapy for RRMM showed good tolerability and outstanding anti-myeloma activity, especially in EMM patients. GR1803 has the potential to improve outcomes for RRMM patients. With extended follow-up, more data on efficacy and safety will be provided in subsequent studies.
Oncology Frontier – Hematology Frontier: We noticed that GR1803 showed good efficacy in EMM patients. What is the significance of this for the treatment of RRMM? What impact do you think this finding will have on future research and treatment strategies?
Professor Jie Jin: In this phase I monotherapy study for RRMM patients, we specifically focused on patients with extramedullary multiple myeloma (EMM). Among the 13 EMM patients included, all completed at least one cycle of efficacy evaluation. Encouragingly, 7 of these patients achieved VGPR, which is a significant advancement. As we know, traditional treatment options are often limited for patients with extramedullary relapse, and many clinical trials exclude these patients. However, the inclusion criteria for the GR1803 study did not exclude these patients, offering them a chance for treatment. The results demonstrated that GR1803 showed good efficacy in these patients, providing new possibilities for this challenging patient population. With the launch of bispecific antibodies, we expect more and better treatment options for multiple myeloma patients. We look forward to the successful completion of clinical trials for GR1803 and its early approval, benefiting more patients.
Oncology Frontier – Hematology Frontier: Could you briefly introduce the studies from your team selected for EHA, and what impact will these studies have on future treatment?
Professor Jie Jin: At this year’s EHA Annual Meeting, our research team from the First Affiliated Hospital of Zhejiang University School of Medicine had the honor to present more than ten clinical research findings covering various hematological fields, including myelodysplastic syndromes (MDS), leukemia, and myelofibrosis (MF). Notably, in the treatment of myelofibrosis, two studies achieved significant progress and encouraging results. One study, a phase III clinical trial (P1054), compared the efficacy of Jaktinib versus hydroxyurea in treating intermediate/high-risk newly diagnosed myelofibrosis patients. The results showed that Jaktinib significantly reduced spleen size compared to hydroxyurea at 24 weeks, offering a new treatment option for myelofibrosis patients.
Another study focused on the use of Jaktinib in treating myelofibrosis patients with anemia (P1031). The results showed that more than 40% of patients experienced significant improvement in anemia after Jaktinib treatment, providing a significant benefit, especially for those intolerant to ruxolitinib.
The clinical research results presented at the 2024 EHA Annual Meeting highlight China’s deep research and innovation capabilities in hematologic oncology and bring new hope to Chinese hematologic cancer patients. These studies suggest that future treatment strategies will be more diverse and personalized. Let us look forward to the continuous improvement of our diagnosis and treatment levels, bringing better well-being to patients.
Key Research Highlights from Professor Jie Jin’s Team
- Abstract Number: P961 Title: A PHASE I MONOTHERAPY STUDY ASSESSING THE SAFETY AND EFFICACY OF GR1803, A BCMA×CD3 BISPECIFIC ANTIBODY, IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA
First Author: Min Yang
Corresponding Author: Jie Jin
- Abstract Number: P1960 Title: EFFICACY AND SAFETY OF TALQUETAMAB, A GPRC5D×CD3 BISPECIFIC ANTIBODY, IN CHINESE PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA FROM THE PHASE 1/2 MONUMENTAL-1 STUDY
First Author: Gang An (Institute of Hematology, Chinese Academy of Medical Sciences)
Corresponding Author: Jie Jin
- Abstract Number: P1031 Title: UNVEILING THE EFFECTIVENESS AND PREDICTIVE FACTORS OF JAKTINIB TREATMENT IN MYELOFIBROSIS PATIENTS WITH ANEMIA
First Author: Huafeng Wang
Corresponding Author: Jie Jin
- Abstract Number: P1054 Title: COMPREHENSIVE EVALUATION OF JAKTINIB VERSUS HYDROXYUREA IN PATIENTS WITH INTERMEDIATE-2 OR HIGH RISK MYELOFIBROSIS: FINAL ANALYSIS RESULTS FROM A RANDOMIZED PHASE 3 STUDY
First Author: Huafeng Wang
Corresponding Author: Jie Jin
- Abstract Number: PB2474 Title: VENETOCLAX PLUS HOMOHARRINGTONINE WITH CYTARABINE AND ACLARUBICIN AS INDUCTION THERAPY FOR YOUNG ADULTS WITH DE NOVO ACUTE MYELOID LEUKEMIA: A PROSPECTIVE, SINGLE-ARM, MULTICENTER, PHASE 2 STUDY
First Author: Huafeng Wang
Corresponding Author: Jie Jin
