2021 IMW Big Coffee Commentary｜Professor Liu Aijun's interpretation of the Phase I study of elranatamab in the treatment of RRMM

Elranatamab (PF-06863135) is a humanized bispecific antibody that targets B cell maturation antigen (BCMA) and CD3 on T cells
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MagnetisMM-1 study (NCT03269136) is a phase I clinical study aimed at exploring the efficacy, safety, and pharmacokinetics of elranatamab and its combined immunomodulators in the treatment of patients with relapsed and refractory multiple myeloma (RRMM) And pharmacodynamics
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The research results will be announced at the IMW meeting in 2021, and Yimaitong specially invited Professor Liu Aijun from Beijing Chaoyang Hospital to comment on this
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Study method Patients received elranatamab 80, 130, 215, 360, 600 or 1000 μg/kg by subcutaneous injection once a week
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The modified toxicity probability interval method was used for dose escalation, and dose-limiting toxicity (DLT) was monitored to the end of the first cycle
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"Treatment period" adverse events (TEAE) are graded according to the general terminology criteria for adverse events (v4.
03), and cytokine release syndrome (CRS) is graded according to the standards of the American Society for Transplantation and Cell Therapy
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Evaluate remission and minimal residual disease (MRD) status according to the standards of the International Myeloma Working Group (assessed by next-generation sequencing [sensitivity of 1×10-5])
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In addition, the study also conducted pharmacokinetics, cytokine profile analysis and T cell immunophenotyping analysis
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The results of the study as of February 4, 2021, a total of 30 patients (80μg/kg, 6 cases; 130μg/kg, 4 cases; 215μg/kg, 4 cases; 360μg/kg, 4 cases; 600μg/kg, 6 cases; 1000μg/kg, 6 cases) received elranatamab treatment
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The median number of patients' previous treatment was 8
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87% of patients were triple refractory, 97% of patients had previously received anti-CD38 therapy, and 23% of patients had previously received BCMA-targeted antibody drug conjugate or chimeric antigen receptor T cell therapy
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Common TEAEs include lymphopenia (n=25, 83%; 20% is grade 3, 63% is grade 4), CRS (n=22, 73%; no events> grade 2), anemia (n=18 , 60%; 50% is grade 3, no grade 4 events), neutropenia (n=16, 53%; 23% is grade 3, 30% is grade 4), thrombocytopenia (n=16 , 53%; 17% were grade 3, 20% were grade 4) and local injection site reactions (n=15, 50%; no events> grade 2)
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CRS and immune effector cell-related neurotoxicity syndrome (n=6, 20%) were both ≤2 grade, and the median duration was 3 days and 2.
5 days, respectively
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No DLT was observed
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The overall response rate (ORR) of patients receiving ≥215µg/kg dose treatment is 70% (n=14/20), including partial response (PR; n=1), very good partial response (VGPR; n=7), Complete remission (CR; n=1) and strict complete remission (sCR; n=5)
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Most sCR patients achieve MRD negative
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The median time to remission was 22 days
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In the ≥215 µg/kg dose group, 3 of 4 patients (75%) who had previously received targeted BCMA therapy achieved remission
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The ORR of patients receiving the recommended phase 2 dose (RP2D) 1000μg/kg treatment was 83% (n=5/6)
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The study concluded that the ORR of Elranatamab in the treatment of RRMM patients with RP2D administration reached 83%, and the safety was controllable
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These results confirm the feasibility and potential of targeted BCMA immunotherapy to treat malignant plasma cell diseases, and support further research and exploration of elranatamab in the treatment of MM patients
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Professor Liu Aijun commented that bispecific antibodies, CAR-T cells, and antibody-drug conjugates (ACD) targeting BCMA are currently the hot topics in the field of MM research
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Bispecific antibodies still have a good effect on refractory MM after CAR-T cell therapy and ADC treatment, and are therefore highly anticipated
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The MagnetisMM-1 study is a phase I clinical study of elranatamab (PF-06863135), a humanized bispecific antibody
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The IMW meeting reported the latest results of the Phase I study of MagnetisMM-1, which confirmed that elranatamab can achieve deep remission in patients with multi-line therapy, multi-drug exposure, and even drug-resistant RRMM patients, with rapid onset of action, and targeted targeting in the past.
The RRMM patients treated by BCMA still have good curative effect and the safety is controllable
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In general, humanized bispecific antibodies have definite efficacy and controllable safety.
With the display of more research results in the future, it will definitely bring better treatment options to RRMM patients
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References: Bhagirathbhai Dholaria, et al.
2021 IMW.
OAB-026.
Professor Liu Aijun, Chief Physician, Associate Professor, Doctor of Medicine, Master Tutor, Beijing Chaoyang Hospital, Capital Medical University, Deputy Chairman and Secretary-General, Hemostasis and Thrombosis Branch of China Medical Education Association Member of the Standing Committee of the Myeloma Branch of the Chinese Medical Education AssociationMember of the Standing Committee of the Pharmaceutical Professional Committee of the Chinese Women Physicians Association Member of the Standing Committee of the Thrombus Branch, Member of the Standing Committee of the Fertility Protection and Preservation Committee of the Chinese Human Health Science and Technology Association Visiting scholars of the Institute Research fields: Hematological tumors, mainly including plasma cell tumors, tumors and blood coagulation.
The first participant to participate in the research of National Nature, Beijing Nature, and the First Fund.
The first or corresponding author publishes SCI in Journal of Hematology & Oncology and other journals.
, There are more than 30 core journal papers and 6 monographs
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