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Some very important and exciting news for the myeloma community ensued late last week.
 
The much-awaited outcome of the March 15th FDA Oncologic Drugs Advisory Committee (ODAC) public advisory meeting is finally here.
 
On Friday, March 15, panelists at the advisory meeting thoroughly discussed the risk-benefit assessment of CAR T-cell therapies, Bristol Myers Squibb and 2seventy bio’s Abecma (idecabtagene vicleucel or ide-cel) and Johnson & Johnson and Legend Biotech’s Carvykti (ciltacabtagene autoleucel or cilta-cel).
 
As I mentioned in my last blog, after much deliberation, the ODAC committee panelists voted favorably for Carvykti (11-0) and Abecma (8-3).
 
Recommendations made by the ODAC advisory committee for both CAR T therapies were considered by the FDA during its review of the supplemental Biologics License Applications (sBLA) submitted by both Johnson & Johnson (for Carvykti) and Bristol Myers Squibb (for Abecma).
 
The IMF is very pleased to announce that both CAR T therapies have been approved by the FDA, one after the other.

Abecma: FDA-approved for Triple-Class Exposed RRMM After Two Prior Lines of Therapy

According to a press release from Bristol Myers Squibb: "On April 4, 2024, the U.S. Food and Drug Administration (FDA) approved Abecma® (idecabtagene vicleucel; ide-cel) for the treatment of adult patients with relapsed or refractory multiple myeloma after two or more prior lines of therapy including an immunomodulatory agent (IMiD), a proteasome inhibitor (PI), and an anti-CD38 monoclonal antibody, based on results from the KarMMa-3 trial. This approval expands Abecma’s indication, making it available in earlier lines to patients who have relapsed or become refractory after exposure to these three main classes of treatment (triple-class exposed), after two prior lines of therapy."

 
Earlier Treatment Offers Meaningful Treatment-Free Intervals

The press release notes that “expanded approval brings this personalized CAR T cell therapy to more patients with relapsed or refractory multiple myeloma earlier in their treatment journey as a one-time infusion offering meaningful treatment-free intervals when responding to therapy. Abecma is now approved in the U.S., Japan, Switzerland, and the EU for earlier use for triple-class exposed relapsed and/or refractory multiple myeloma.”
 
“Abecma has demonstrated a progression-free survival benefit three times that of standard regimens in relapsed or refractory multiple myeloma, and we are now bringing the promise of cell therapy to patients earlier in their treatment journey. This approval underpins our commitment to addressing the unmet needs of more patients living with multiple myeloma by improving upon the current treatment paradigm, and we remain steadfast in our pursuit of innovation and advancing cell therapy research to deliver potentially transformative therapies,” stated Bristol Myers Squibb Senior Vice President and Head of Commercial, Cell Therapy Bryan Campbell.

Safety Profile and Information

“Abecma is administered as a one-time infusion, with a new recommended dose range of 300 to 510 x 106 CAR-positive T cells. Abecma comes with important safety information, including boxed warnings regarding Cytokine Release Syndrome (CRS), Neurologic Toxicities, Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome, Prolonged Cytopenia, and Secondary Hematological Malignancies,” the press release further notes.
 

Carvykti: FDA-approved for Treatment of RRMM After At Least One Prior Line of Therapy

Meanwhile, a press release from Johnson & Johnson announced the FDA’s approval of Carvykti on Friday, April 5th: “the U.S. Food and Drug Administration (FDA) has approved CARVYKTI® (ciltacabtagene autoleucel; cilta-cel) for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent, and are refractory to lenalidomide. With this approval, Carvykti becomes the first and only B-cell maturation antigen (BCMA)-targeted therapy approved for the treatment of patients with multiple myeloma as early as first relapse.”
 

Potential Period Away from MM Treatment as Early as First Relapse

“Expanded indication for this one-time infusion will provide more patients with a potential period away from their multiple myeloma treatment as early as first relapse,” further stated Johnson & Johnson adding that “approval is based on results from the Phase 3 CARTITUDE-4 study, in which treatment with Carvykti in 1-3 prior lines of therapy reduced the risk of disease progression or death by 59 percent compared to standard therapies.”
 
According to Associate Professor at the Medical College of Wisconsin, Division of Hematology and Oncology Dr. Binod Dhakal: “Carvykti demonstrated remarkable efficacy as a personalized, one-time infusion in the earlier treatment of relapsed/refractory multiple myeloma as shown through the CARTITUDE-4 study results. With this approval, I’m excited for patients who may have the opportunity for a treatment-free period for their multiple myeloma as early as first relapse, with the hope of eliminating the burden of having to be on continuous treatment while living with this challenging disease.”
 
“This milestone underscores our commitment to improve outcomes for patients and transform the treatment of multiple myeloma with Carvykti. We are proud to bring an important, highly effective immunotherapy that has demonstrated a favorable benefit/risk profile to physicians and patients for the earlier treatment of relapsed/refractory multiple myeloma, and we look forward to building on this latest milestone as we continue to focus on our ultimate goal of delivering a cure for multiple myeloma," said Johnson & Johnson Innovative Medicine Vice President and Disease Area Leader, Multiple Myeloma Dr. Jordan Schecter.

Safety Profile and Information

According to Johnson & Johnson: “The safety profile for Carvykti includes a boxed warning for Cytokine Release Syndrome (CRS), Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), Parkinsonism and Guillain-Barre syndrome and their associated complications, Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS), Prolonged and Recurrent Cytopenias and Secondary Malignancies including myelodysplastic syndrome, acute myeloid leukemia, and T-cell malignancies. Warnings and Precautions include Increased Early Mortality, Hypogammaglobulinemia, Infections, Hypersensitivity Reactions and Effects on Ability to Drive and Use Machines.”
 
“The most common nonlaboratory adverse reactions (incidence greater than 20%) are pyrexia, cytokine release syndrome, hypogammaglobulinemia, hypotension, musculoskeletal pain, fatigue, infections-pathogen unspecified, cough, chills, diarrhea, nausea, encephalopathy, decreased appetite, upper respiratory tract infection, headache, tachycardia, dizziness, dyspnea, edema, viral infections, coagulopathy, constipation, and vomiting. The most common Grade 3 or 4 laboratory adverse reactions (incidence greater than or equal to 50%) include lymphopenia, neutropenia, white blood cell decreased, thrombocytopenia, and anemia.”
 

The Bottom Line

The FDA approval of these highly proven effective CAR T-cell therapies definitely brought an enthusiastic response from the IMF and the myeloma community.

The IMF continues to be at the forefront of these ODAC proceedings, with another one coming up tomorrow, April 12, where the committee will be “discussing the use of minimal residual disease (MRD) as an endpoint in multiple myeloma clinical trials, including considerations regarding timing of assessment, patient populations, and trial design for future studies that intend to use MRD to support accelerated approval of a new product or a new indication,” as stated in the FDA advisory. 

The IMF will definitely make our presence felt at the advisory meeting, on behalf of the myeloma community we serve.

As I have previously emphasized, it is extremely important for clinicians, patients, and patient advocates to have a voice in these ODAC committee meetings. The IMF will be at front and center, providing you with the latest updates on the outcome.

Stay tuned for my next blog!


Image of Dr. Brian G.M. DurieProfessor of Medicine, Hematologist/Oncologist, and Honoree MD at the University of Brussels, Dr. Brian G.M. Durie is Chairman Emeritus and Chief Scientific Officer of the IMF. Dr. Durie is also the Chairman of the International Myeloma Working Group (IMWG)—a consortium of more than 250 myeloma experts from around the world—and leads the IMF’s Black Swan Research Initiative® (BSRI). 

 

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