In May 2023, a multicenter study led by Professor KaiLin Xu's team from Blood Diseases Institute, Xuzhou Medical University was published in the top international academic journal——Journal of Clinical Oncology(IF=50.717), titled "Anti-G Protein-Coupled Receptor, Class C Group 5 Member D Chimeric Antigen Receptor T Cells in Patients With Relapsed or Refractory Multiple Myeloma: A Single Arm, Phase II Trial". This study showed that anti-GPRC5D CAR-T cells have good safety in patients with relapsed/refractory (R/R) multiple myeloma(MM), including those who have progressed or become ineffective after anti-BCMA CAR-T treatment, with an effective rate of 91% and a complete response rate of over 60%. Anti-GPRC5D CAR-T is another promising new type of CAR-T after anti-BCMA CAR-T, with broad application prospects. This study was also recently selected as one of the "China’s Top 10 Research Advances in Hematology in 2023".
Multiple myeloma (MM) is a challenging hematologic cancer characterized by uncontrollable plasma cell proliferation in the bone marrow. Despite advancements in MM treatments, relapse or refractory cases are common. Chimeric Antigen Receptor (CAR) T-cell therapy has emerged as a promising avenue, initially targeting B-cell maturation antigen (BCMA). However, issues like relapse and BCMA antigen loss have led to the exploration of alternative targets.
GPRC5D, highly expressed on malignant plasma cells and minimally on normal tissues, is an ideal target for CAR-T-cell therapy due to its selectivity. The Phase II clinical trial led by Professor Kailin Xu’s team enrolled 33 relapsed or refractory MM patients to evaluate the therapeutic effect of Anti-GPRC5D CAR-T-cell therapy. Patient selection criteria and treatment protocols were meticulously defined, including lymphodepletion therapy to enhance CAR-T-cell infusion efficacy.
At a median follow-up of 5.2 months, the trial achieved a remarkable overall response rate of 91%(30/33). Notably, 11(33%) had stringent complete responses, and 10(30%) had complete responses. Very good partial responses were seen in 4(12%), and 5(15%) exhibited partial responses. All nine patients who had previously received anti-BCMA CAR-T therapy responded positively , offering hope to those with prior treatment failures.
The trial demonstrated a manageable safety profile, with common hematologic toxicities and mild cytokine release syndrome. Neurotoxicities were observed but generally low-grade and treatable. The data indicates a favorable safety profile for this CAR-T cell therapy. CAR-T cell expansion peaked between days 14 and 28 post-infusion, with 48% of patients retaining detectable CAR-T cells at three months.
The Phase II trial of Anti-GPRC5D CAR-T-cell therapy offers hope for relapsed or refractory MM patients. High response rates and manageable safety profiles mark a significant milestone.For patients with MM that progressed after anti-BCMA CAR T-cell therapy or that is refractory to anti-BCMA CAR T cell, anti-GPRC5D CAR T-cell therapy might be a potential alternative option. While promising, larger studies and longer follow-up periods are needed to validate these findings. Investigating therapy in various MM stages and optimizing sequencing are crucial.
