Zevorcabtagene autoleucel for multiple myeloma
Fact-checked by What is zevor-cel for multiple myeloma?
Zevorcabtagene autoleucel, or zevor-cel, is a CAR T-cell therapy being developed by Carsgen Therapeutics for people with multiple myeloma.
Although not approved in the U.S., zevor-cel is approved in China for adults whose myeloma has not responded to (refractory) or returned after (relapsed) at least three prior lines of treatment.
Multiple myeloma is a type of blood cancer that affects immune plasma cells in the bone marrow. Cancerous plasma cells, or myeloma cells, grow out of control and may evade natural anti-cancer immune mechanisms.
As with other CAR T-cell therapies, zevor-cel aims to improve the ability of T-cells, a kind of immune cell, to recognize and attack myeloma cells. After T-cells are collected from a patient’s blood, they are engineered in a lab to carry a chimeric antigen receptor, or CAR, that specifically recognizes a protein on the surface of myeloma cells. The CAR used in zevor-cel targets B-cell maturation antigen (BCMA).
Patients then receive an into-the-vein (intravenous) infusion of their modified cells, which are expected to better recognize and attack cancerous plasma cells.
In the U.S., zevor-cel holds orphan drug and regenerative medicine advanced therapy designations, which are statuses intended to speed its clinical development. Beyond multiple myeloma, Carsgen announced plans to partner with Dispatch Bio to explore the use of zevor-cel in certain solid tumor cancers.
Therapy snapshot
| Treatment name | Zevorcabtagene autoleucel |
| Administration | Intravenous infusion |
| Clinical testing | Currently in Phase 1/2 clinical testing |
How will zevor-cel be administered in multiple myeloma?
Manufacturing and administering zevor-cel involves several steps:
- Cell collection: T-cells are collected from the patient’s blood.
- Cell modification: The collected T-cells are engineered in a lab to carry the BCMA-targeting CAR. This takes approximately three weeks.
- Pre-infusion treatment: Patients receive three days of chemotherapy to reduce immune cell levels, preparing the body for the zevor-cel infusion.
- Zevor-cel infusion: An intravenous infusion returns the engineered CAR T-cells to the body.
In an ongoing Phase 2 study, the zevor-cel infusion contained about 150-180 million CAR T-cells, depending on the participants’ weight.
Zevor-cel in multiple myeloma clinical trials
The Chinese approval of zevor-cel was based on results from the Phase 1/2 LUMMICAR STUDY 1 (NCT03975907), which involved adults with relapsed or refractory multiple myeloma who had received at least three prior lines of therapy.
The Phase 1 part of the trial included 14 participants who received a dose of either 100 million or 150 million CAR T-cells. The data showed:
- all participants had at least a partial response to treatment, or a decrease in myeloma activity, while 78.6% had a complete response or better, with no signs of active myeloma
- participants remained alive without disease progression for a median of 25.8 months (just over two years), and 76.9% of participants were still alive after five years
In the larger Phase 2 part, 102 people received the selected dose of 150 million CAR T-cells (or 180 million for heavier participants). Data demonstrated:
- most participants (92.2%) had at least a partial response to treatment, and 71.6% had at least a complete response
- after one year of follow-up, 76.3% of participants were alive and hadn’t experienced disease progression
- efficacy was similar across subgroups of participants, including individuals with high-risk disease characteristics
The Phase 1/2Â LUMMICAR STUDY 2 (NCT03915184), designed similarly to LUMMICAR STUDY 1, is testing the therapy among participants in the U.S. and Canada.
Based on the Phase 1 results, investigators selected a dose of 180 million CAR T-cells for the Phase 2 part. Preliminary efficacy results from 11 participants in the Phase 2 part showed that all had at least a partial response.
Zevor-cel side effects
Across both phases of LUMMICAR STUDY 1, some of the most common side effects included:
- decreased blood cell counts
- fever
- changes in blood levels of certain nutrients, such as potassium or calcium
- infection
- diarrhea or other gastrointestinal problems
- low blood pressure
- cytokine release syndrome (CRS), a type of whole-body inflammatory response
While CRS was common, occurring in about 90% of Phase 2 participants, most cases were mild or moderate and all cases resolved.
Immune effector cell-associated neurotoxicity syndrome (ICANS), a potential neurological complication of cell therapies, occurred in 2% of Phase 2 participants. These cases were mild and resolved. The most common non-ICANS neurological symptoms were dizziness and headaches.
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