CAR-T And Multiple Myeloma:The Road Ahead for CAR-T Cell Therapy in Multiple Myeloma,Arduous yet Promising

CAR-T And Multiple Myeloma:The Road Ahead for CAR-T Cell Therapy in Multiple Myeloma,Arduous yet Promising

In the near future, CAR-T cell therapy products for multiple myeloma will gradually be launched in China and soon enter clinical practice, which is good news. However, we still face many pressing real-world issues that need to be addressed.

Car-t in the treatment of multiple myeloma

First, after the CAR-T products are launched, their high prices may deter some patients from pursuing this treatment option. Conservative estimates suggest that each CAR-T cell therapy could cost no less than 1 million Chinese yuan (RMB). The CAR-T product developed by Nanjing Legend Biotech (Carvykti, ciltacabtagene autoleucel) has already been launched in the United States, currently priced at $465,000 (approximately RMB 2.93 million); Bristol Myers Squibb and Bluebird Bio’s CAR-T therapy Abecma (idecabtagene vicleucel) was approved in March 2021, priced at $415,000 (approximately RMB 2.7 million).

Second, while CAR-T therapy for multiple myeloma has shown promising efficacy, it does not equate to a cure, as almost all patients still face the risk of relapse and disease progression. Therefore, even if CAR-T therapy becomes widely available, it is not the ultimate treatment for multiple myeloma, and close monitoring of the disease is still necessary after treatment.

Third, the optimal sequential therapy after CAR-T treatment is currently unclear. Since a cure cannot be achieved, some form of drug therapy should be considered after CAR-T treatment, ideally agents that not only do not impair the function of the remaining CAR-T cells but also enhance their efficacy and anti-tumor effects, leading to durable disease control.

Fourth, current data indicate that multiple myeloma patients with extramedullary disease may not achieve lasting remission from CAR-T therapy alone. Even if initially effective, progression is likely to occur. Therefore, relapsed/refractory patients with extramedullary disease should consider chemotherapy to effectively control the extramedullary disease before proceeding with sequential CAR-T therapy.

Fifth, current evidence more strongly supports the use of CAR-T therapy for relapsed/refractory multiple myeloma patients who are at least triple-refractory. There is currently a lack of sufficient data to support the frontline use of CAR-T therapy in multiple myeloma. Some centers are exploring the use of CAR-T therapy as consolidation after autologous stem cell transplantation in high-risk patients, with preliminary results showing good clinical efficacy and safety. However, more data is needed to establish the feasibility of CAR-T therapy in the frontline setting, which would first need to address the substantial cost issue.

Despite these challenges, the advent of CAR-T products has brought a glimmer of hope for multiple myeloma patients who have progressed through multiple lines of therapy and developed multi-drug resistance. Although the obstacles are numerous, I believe that the pricing issue may only be a matter of time, as more products become available and commercial insurance coverage becomes more effective.

Furthermore, real-world data have shown that some relapsed/refractory patients who received CAR-T cell therapy can still exhibit decent treatment responses even when their disease progresses. In other words, progression after CAR-T therapy does not necessarily warrant excessive concern.

I have been advocating for “standardized diagnosis and treatment,” which not only facilitates durable disease control but also effectively reduces medical expenses for patients. Recently, I proposed the concept of “using each effective treatment to its full potential,” which is also an essential part of “standardized diagnosis and treatment.” We all know that many new drugs are not immediately included in medical insurance coverage, and CAR-T therapy is unlikely to be covered by insurance in the short term. Since the treatment of multiple myeloma is a long-term battle, standardized diagnosis and treatment ensure that we maximize treatment efficacy for multiple myeloma patients while strategically reducing economic burden.

I have been strongly promoting upfront autologous stem cell transplantation for the treatment of multiple myeloma, as the role of autologous transplantation has not been supplanted by any new drugs – and CAR-T therapy is unlikely to displace autologous transplantation in the short term. Whether it is new drug therapy, autologous transplantation, or CAR-T therapy, all are part of the treatment for multiple myeloma. Optimizing treatment strategies will be our important task for the foreseeable future.

A objective, calm, and rational understanding of CAR-T therapy will enable us to better apply this treatment to the most appropriate population of multiple myeloma patients. I will continue to closely monitor the launch of CAR-T products.

While the road ahead may be thorny and rugged, we remain confident in welcoming CAR-T therapy.

Once again, a reminder: All multiple myeloma patients should follow standardized diagnosis, treatment, and follow-up. Patients eligible for transplantation should undergo upfront autologous stem cell transplantation, with high-risk patients recommended for sequential autologous transplantation. Remember, complete remission does not equate to a cure.