FDA to decide on Carvykti by April 5th, no date set yet for Abecma. European Commission (EC) approves Abecma for early treatment of RRMM in the European Union (EU) on March 20.


On Friday, March 15, the U.S. Food and Drug Administration (FDA) held an Oncologic Drugs Advisory Committee (ODAC) public advisory committee meeting to discuss the risk-benefit assessment of two CAR T-cell therapies: Johnson & Johnson and Legend Biotech’s Carvykti (ciltacabtagene autoleucel or cilta-cel) and Bristol-Myers Squibb and 2seventy bio’s Abecma (idecabtagene vicleucel or ide-cel). 

The ODAC is an FDA advisory committee that “reviews and evaluates data concerning the safety and effectiveness of marketed and investigational human drug products for use in the treatment of cancer and makes appropriate recommendations to the Commissioner of Food and Drugs,” according to the FDA.

The ODAC committee panelists deliberated on the use of Carvykti and Abecma on relapsed/refractory multiple myeloma (RRMM) patients as early as the first relapse. 

The International Myeloma Foundation (IMF) was at the forefront of the proceedings, with IMF President & CEO and 28-year myeloma survivor Yelak Biru, IMF Board Members Jack Aiello and Sanjay Singh, and yours truly among those who provided oral testimonials for both the Carvykti and Abecma proceedings. I also highly commend the participation of Carl Burgman, Linda Huguelet, and other myeloma patient/advocates during the meeting. It is extremely important for clinicians, patients, and patient advocates to have a voice in these ODAC committee meetings.

In case you missed it, you can still watch the proceedings via a recorded YouTube video.

Carvykti Gets Unanimous Vote (11-0)

In June 2023, Johnson & Johnson (Janssen Biotech, Inc., Janssen) submitted a supplemental Biologics Licensing Application (sBLA) for Carvykti, to seek approval for proposed indication and recommended dosage and along with it, the results of the CARTITUDE-4 trial where the FDA noted that the study “met its primary endpoint, demonstrating a statistically significant improvement in progression-free survival (PFS) in patients randomized to the cilta-cel arm compared to patients randomized to the control arm.” 

Safety Concern

However, findings from the CARTITUDE-4 trial also showed that “deaths due to adverse effects (AE) were higher in the cilta-cel arm (11 percent) compared to the deaths in the standard therapy arm (8 percent).” The main topic for discussion during the advisory meeting was the “increased number of early deaths in the cilta-cel arm,” according to the FDA briefing document. 

Favorable Risk-Benefit Assessment

After the ODAC proceedings, the committee voted unanimously (11-0), “supporting favorable risk-benefit assessment of Carvykti (cilta-cel),” according to a press release from Johnson & Johnson. 

The committee’s decision was based on a thorough review of the survival and safety data from the Phase 3 CARTITUDE-4 study, with data “evaluating the efficacy and safety of Carvykti vs pomalidomide, bortezomib, and dexamethasone (PVd) or daratumumab, pomalidomide, and dexamethasone (DPd) in the treatment of patients with relapsed and lenalidomide-refractory multiple myeloma who received one to three prior lines of therapy.” 

Carvykti (cilta-cel) has been recommended by the advisory committee “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 (PI) and an immunomodulatory agent (IMiD) and who are refractory to lenalidomide.” However, it is important to note that the committee’s recommendation is non-binding; it is still up to the FDA to make the final decision on approval.

“A supplemental Biologics License Application (sBLA) supported by the CARTITUDE-4 study is currently under review by the FDA with a Prescription Drug User Fee Act (PDUFA) date of April 5, 2024,” stated the press release further.

Importance of Cilta-cel to the Unmet Needs of RRMM Patients

Johnson & Johnson Innovative Medicine Vice President and Disease Area Leader for Multiple Myeloma Jordan Schecter M.D. “was very pleased with the advisory committee’s support for Carvykti in earlier lines of treatment based on the CARTITUDE-4 data.”

"As a physician and researcher committed to advancing patient care, the potential of Carvykti in earlier lines of therapy represents an important therapeutic option for patients with multiple myeloma,” said Dr. Schecter.

According to Sundar Jagannath, MBBS, Director of the Center of Excellence for Multiple Myeloma and Professor of Medicine (Hematology and Medical Oncology) at the Tisch Cancer Institute (Mount Sinai Hospital—New York, NY): "Multiple myeloma is a disease with high unmet need as patients experience relapse or become refractory to treatments over time. The availability of a cellular therapy like cilta-cel that can be used earlier in the treatment of this progressive disease is critically important, offering patients a chance of deep and durable responses with a one-time infusion."

Abecma Secures ODAC Majority Vote (8-3)

For Abecma (ide-cel) and the results of the KarMMa-3 trial, the FDA noted that “KarMMa-3 met its primary endpoint, demonstrating a statistically significant improvement in PFS in patients randomized to the ide-cel arm compared to patients randomized to the control arm.”

Safety concern

However, the FDA was particularly interested in the committee’s opinion “regarding the higher rate of early deaths in the ide-cel arm, in the context of statistically significant PFS benefit in the KarMMa-3 trial,” according to the FDA briefing document.

Favorable Risk-Benefit Assessment

After much deliberation and analysis of data from the KarMMa-3 trial, the committee decided “that Abecma (ide-cel) demonstrated a favorable benefit/risk profile for patients with triple-class exposed relapsed or refractory multiple myeloma based on results from the pivotal Phase 3 KarMMa-3 study, including the key secondary endpoint of overall survival,” according to a press release from Bristol Myers Squibb and 2seventy bio. 

“The positive vote from the ODAC followed discussion of the interim overall survival data from the KarMMa-3 study,” stated the press release.

“The recommendation from the ODAC will be considered by the FDA during its ongoing review of the supplemental Biologics License Application (sBLA) for Abecma for this patient population. The FDA has not yet assigned a new target action date for review of the sBLA,” noted the press release. 

Significant Clinical Benefit of Ide-cel

Bristol Myers Squibb Senior Vice President and Head of Late Clinical Development, Hematology, Oncology, and Cell Therapy Anne Kerber was “extremely pleased with the positive outcome of the ODAC meeting, which recognizes the favorable benefit/risk profile of Abecma.”

“Based on results from the KarMMa-3 study, we are confident in the significant clinical benefit that Abecma delivers for patients with triple-class exposed relapsed or refractory multiple myeloma, an incurable disease with no clear effective standard of care in earlier lines of therapy. We look forward to working with the FDA as it completes review of our sBLA in order to bring this potentially transformative therapy to more patients in need,” said Kerber. 

Chief Medical Officer of the Winship Cancer Institute (Emory University—Atlanta, GA) and Professor and Chair (Dept. of Hematology and Medical Oncology, Emory University School of Medicine) Sagar Lonial, MD, FACP stated that “with patients becoming triple-class exposed earlier in the multiple myeloma treatment paradigm, it is critical that new treatment options with the potential to improve long-term outcomes are available as early as possible.” 

“We are thankful that today’s ODAC vote recognizes this unmet need and helps to advance ide-cel, a novel treatment option with demonstrated clinically meaningful benefit, for patients with triple-class exposed relapsed or refractory multiple myeloma,” he further added.

Abecma: First CAR T Approved by the European Commission for Early Treatment of RRMM in the EU

Meanwhile, the European Commission (EC) has granted approval to Abecma on March 20 “for the treatment of adult patients with relapsed and refractory multiple myeloma who have received at least two prior therapies, including an immunomodulatory agent (IMiD), a proteasome inhibitor (PI), and an anti-CD38 antibody and have demonstrated disease progression on the last therapy. Abecma is the first chimeric antigen receptor (CAR) T cell immunotherapy approved in the European Union (EU) for use in earlier lines of therapy for relapsed and refractory multiple myeloma. This expanded approval of Abecma covers all EU member states.* In the EU, Abecma has maintained its Orphan Designation for the treatment of multiple myeloma,” stated BMS in a press release. 
*Centralized Marketing Authorization does not include approval in Great Britain (England, Scotland, and Wales)
“[March 20’s] approval in the European Union marks an exciting milestone in our efforts to bring the transformative potential of cell therapies into earlier lines of treatment. Abecma is an important treatment option for patients with triple-class exposed relapsed and refractory multiple myeloma who have received at least two prior therapies and is leading the way toward a promising shift in the treatment paradigm,” said Bristol Myers Squibb Senior Vice President and Head of European Markets Monica Shaw, M.D.
According to Specialist in Hematology and Hemotherapy and Medical Coordinator of the Central Unit for Clinical Trials Paula Rodriguez-Otero, M.D., Ph.D., (Department of Hematology, Clinica Universidad de Navarra—Pamplona, Spain): “As patients with multiple myeloma become exposed to the three main classes of therapy earlier in treatment and still experience relapsed and/or refractory disease, it is critical that we continue to add innovative treatment options to our arsenal that can potentially provide long-term disease control. This expanded approval of ide-cel represents key progress in bringing a personalized therapy that delivers significantly improved, durable outcomes to patients with triple-class exposed relapsed and refractory multiple myeloma after two prior therapies.”

The Bottom Line

From my perspective, both CAR T therapies are dramatically beneficial and deserve to be made available to patients earlier in the disease course. 

Clearly, expert care is necessary to guide patients through known toxicities (including CRS plus early and delayed neurotoxicities) to achieve best outcomes. 

As made clear by the ODAC’s decision for both CAR T treatments, potential benefits outweighed known risks. Having these CAR T therapies available for earlier use is an important option for patients seeking to achieve excellent quality of life outcomes with, for example long, durable remissions off all therapy.

However, please note that the ODAC’s recommendations are non-binding, and that it is still up to the FDA to make the final decision when it comes to the approval of these CAR T treatments.

The International Myeloma Foundation (IMF) will continue to actively monitor the ongoing FDA sBLA reviews for Carvykti and Abecma. Meanwhile, stay tuned for updates on the IMF website and on the IMF’s social media channels: Facebook, LinkedIn, Instagram, and X

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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