Yi Lin, MD, PhD, hematologist, oncologist, Department of Hematology, CAR T-Cell Therapy Program, Mayo Clinic, discusses treatment updates in CAR T-cell therapy in multiple myeloma.

CD19-targeted CAR T-cell therapy has established a role in various leukemias and lymphomas. However, in multiple myeloma, CAR T-cell therapy has been developed to target BCMA plasma cells, which serves as a strong proof of concept for CAR T-cell therapy, Lin says. By targeting different tumor markers, CAR T-cell therapy can be expanded into other cancer types, Lin explains.

CAR T-cell therapy remains a logistically complex treatment that is still not readily available in all oncology clinics, Lin continues. These treatments must be given at specific centers that have the multidisciplinary expertise and the ability to provide this treatment, Lin concludes.

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Yi Lin, MD, PhD, discusses treatment updates in CAR T-cell therapy in multiple myeloma.


Dr. Lin on Treatment Updates in CAR T-Cell Therapy in Myeloma

Yi Lin, MD, PhD, consultant, Division of Hematology, Department of Internal Medicine, consultant, Division of Experimental Pathology and Laboratory Medicine, Department of Laboratory Medicine and Pathology, assistant professor of medicine and oncology, Mayo Clinic, discusses the importance of developing non-BCMA–targeting agents in multiple myeloma.

Multiple BCMA-directed CAR T-cell therapies, bispecific antibodies, and antibody-drug conjugates are demonstrating significant efficacy for patients with multiple myeloma. However, the field is developing non-BCMA–targeted options as well, Lin explains.

Early data with non-BCMA–targeting approaches are showing high rates of early responses in patients, says Lin. With the rapid growth of immunotherapy in multiple myeloma, data will likely emerge in the coming years showing that non-BCMA–directed therapies are good options for patients, concludes Lin. 

Yi Lin, MD, PhD, discusses the importance of developing non-BCMA–targeting agents in multiple myeloma. 



Dr. Lin on the Importance of Developing non-BCMA–Targeting Agents in Myeloma 

Yi Lin, MD, PhD, consultant, Division of Hematology, Department of Internal Medicine, consultant, Division of Experimental Pathology and Laboratory Medicine, Department of Laboratory Medicine and Pathology, assistant professor of medicine and oncology, Mayo Clinic, discusses CAR T-cell therapy–related toxicities in multiple myeloma.

In multiple myeloma, investigational CAR T-cell therapy products do not appear to induce the same degree of severe toxicities as in other hematologic malignancies, explains Lin. For example, as demonstrated in several clinical trials, less than 10% of patients typically develop grade 3 or higher cytokine release syndrome or neurotoxicity that would require monitoring in the intensive care unit, says Lin.

Notably, some contributing factors to this lesser degree of severe toxicities could be the design of the CAR T-cell products, along with the natural aspects of the disease. The field is now trying to gain a greater understanding on how to best utilize interventions, such as tocilizumab (Actemra) and steroids, to retain response while preventing severe toxicities, concludes Lin.

Yi Lin, MD, PhD, discusses CAR T-cell therapy–related toxicities in multiple myeloma.  



Dr. Lin on CAR T-Cell Therapy–Related Toxicities in Multiple Myeloma 

Yi Lin, MD, PhD, an assistant professor of oncology, associate professor of medicine, and a consultant in the Division of Hematology and Division of Experimental Pathology and Laboratory Medicine at Mayo Clinic, discusses the characteristics of patients who were included in the CRB-401 study examining the CAR T-cell product idecabtagene vicleucel (ide-cel; bb2121) in multiple myeloma.


The first results from the CRB-401 study, which included 33 patients, were published in the 

 in May 2019, says Lin. At the 2020 ASH Annual Meeting & Exposition, the results of the full 62-patient cohort were presented at a median follow-up of 14.7 months.


The overall patient cohort that received treatment was comprised of individuals who had high-risk features; approximately one-third of patients had high-risk cytogenetics. Additionally, 37% had extramedullary plasmacytomas and half required a systemic bridging therapy while their CAR T-cell therapy was being manufactured, explains Lin. On average, 45% of patients had received more than 6 prior lines of therapy. Moreover, the majority of patients either had triple-refractory disease or were refractory to their most recent line of therapy, Lin concludes.

Yi Lin, MD, PhD, discusses the characteristics of patients who were included in the CRB-401 study examining the CAR T-cell product idecabtagene vicleucel in multiple myeloma.


Dr. Lin on Patient Characteristics From the CRB-401 Study of Ide-Cel in Myeloma

Yi Lin, MD, PhD, an assistant professor of oncology, associate professor of medicine, and a consultant in the Division of Hematology and Division of Experimental Pathology and Laboratory Medicine at Mayo Clinic, discusses the promise of the CAR T-cell products ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel) in patients with myeloma.

Both cilta-cel and ide-cel are under evaluation in pivotal clinical trials, says Lin. A biologics license application (BLA) has been submitted to the FDA for ide-cel, and the regulatory agency has granted the application priority review. The FDA is anticipated to make a decision on the BLA by March 27, 2021. Additionally, a rolling submission of a BLA for cilta-cel has also been initiated. Both BCMA-directed CAR T-cell products could potentially be available for clinical practice in 2021, says Lin. The trials that have examined these products have evaluated their use in heavily pretreated patient populations with poor-risk cytogenetics and penta-refractory disease.

A single-dose infusion of either of these products in this patient population has been shown to elicit high overall response rates, with many patients achieving complete remissions or stringent complete responses, adds Lin. Notably, many of the patients who achieve remission are also found to have minimal residual disease negativity. These responses are significant in myeloma, especially because they have also proven to be durable, concludes Lin.

Yi Lin, MD, PhD, discusses the promise of the CAR T-cell products ciltacabtagene autoleucel and idecabtagene vicleucel in patients with myeloma.

Dr. Lin on the Promise of Cilta-Cel and Ide-Cel in Myeloma

Yi Lin, MD, PhD, consultant, Division of Hematology, Department of Internal Medicine, consultant, Division of Experimental Pathology and Laboratory Medicine, Department of Laboratory Medicine and Pathology, assistant professor of medicine and oncology, Mayo Clinic, discusse​s updated results of the phase 1 CRB-401 study (NCT02658929) in relapsed/refractory multiple myeloma.

Updated results from the phase 1 CRB-401 study, which were presented ​virtually during the 2020 ASH Annual Meeting ​& Exposition, ​showed that 27.4% of patients evaluated had high-risk cytogenetics and 37.1% ​had extramedullary disease. Notably, 51.6% of these patients required bridging therapy during manufacturing of CAR T cell​s. Patients ​were heavily pretreated, having received​ a median of 6 prior lines of therapy. About 70% ​of patients were ​triple-class refractory or refractory to their most recent prior therapy, Lin says.

 Overall, the patients tolerated idecabtagene vicleucel (ide-cel; bb2121) well. As patients also received lymphodepletion chemotherapy, low blood count was a common adverse effect. However, this ​toxicity is typically resolved within the first 3 months ​following the infusion of CAR T-cell ​therapy, Lin concludes.

Yi Lin, MD, PhD, discusses​s updated results of the phase 1 CRB-401 study in relapsed/refractory multiple myeloma.








Yi Lin, MD, PhD

Articles

Dr. Lin on Treatment Updates in CAR T-Cell Therapy in Myeloma

Dr. Lin on the Importance of Developing non-BCMA–Targeting Agents in Myeloma

Dr. Lin on CAR T-Cell Therapy–Related Toxicities in Multiple Myeloma

Dr. Lin on Patient Characteristics From the CRB-401 Study of Ide-Cel in Myeloma

Dr. Lin on the Promise of Cilta-Cel and Ide-Cel in Myeloma

Dr. Lin on Updated Results of the CRB-401 Trial in Relapsed/Refractory Multiple Myeloma