FDA asked to extend Carvykti to myeloma patients after first relapse
CAR T-cell therapy currently for heavily treated relapsed or refractory MM
Janssen is asking the U.S. Food and Drug Administration (FDA) to expand approval its cell therapy Carvykti (ciltacabtagene autoleucel) to allow for earlier treatment of people with relapsed or refractory multiple myeloma (RRMM).
Carvykti is approved in the U.S. for people with heavily treated myeloma, or patients who had received at least four prior lines of therapy, including a proteasome inhibitor (PI), an immunomodulatory agent (iMiD), and a CD38 inhibitor.
Should Janssen’s new supplemental biologics license application (sBLA) be approved, the indication would include adults with RRMM who have received at least one prior line of therapy, including PIs and iMiDs, and are refractory to Revlimid (lenalidomide).
Janssen has filed a similar application to expand the therapy’s label in Europe to include adults with relapsed and Revlimid-resistant disease. Currently, it is indicated in Europe for adults who failed to respond to at least three prior lines of therapy, including a PI, IMiD, and a CD38 inhibitor.
Earlier use of CAR T-cell therapy in multiple myeloma supported by trial data
“We are focused on advancing Carvykti in the treatment of multiple myeloma, including for patients with relapsed or refractory disease, where we hope to intervene earlier with the goal of transforming outcomes for patients,” Peter Lebowitz, MD, PhD, global therapeutic head of oncology at Janssen research and development, said in a company press release.
“We look forward to collaborating with the FDA on the review of this application and continuing to bring Carvykti to patients who are candidates for this CAR-T therapy,” Lebowitz added.
Formerly known as cilta-cel, Carvykti belongs to a class of treatments called CAR T-cell therapies that are gaining ground for the treatment of certain types of cancer and autoimmune diseases.
Briefly, the one-time treatment involves collecting a patient’s immune T-cells, and modifying them in the lab to be able to target and kill myeloma cells when infused back into the body.
The therapy was co-developed by Legend Biotech and Janssen.
Janssen’s sBLA was backed by data from the Phase 3 CARTITUDE-4 study (NCT04181827), which Janssen touts as the first of its kind to evaluate a cell therapy in RRMM patients as soon as after a first disease relapse.
The trial enrolled 419 adults with myeloma who had failed to respond to Revlimid and up to three other treatments. Participants were randomly assigned to receive Carvykti or standard-of-care treatment and are being followed for up to six years.
Standard treatment could include either of two combinations: the CD38 inhibitor Darzalex (daratumumab) with the IMiD Pomalyst (pomalidomide) and dexamethasone, or Pomalyst, dexamethasone, and Velcade (bortezomib), a PI.
Lower risk of disease progression among patients with one prior therapy line
Trial data indicated that the risk of disease progression or death after about 16 months (nearly 1.5 years) was significantly lower — by 74% — with Carvykti relative to standard care. Notably, the cell therapy was associated with a 65% reduction in risk of progression or death among patients who had received only one prior line of therapy.
Overall, 84.6% of Carvykti-treated patients responded to the therapy, compared with 67.3% in the standard care group.
Patients on Carvykti also were more likely to show a complete response or to have no detectable cancer cells on follow-up tests.
Virtually all trial participants experienced severe side effects, with the most common being low blood cell counts and infections. These rates were similar in the Carvykti and standard care groups.
Most Carvykti-treated patients (76.1%) experienced cytokine release syndrome, a severe type of inflammatory response that is a known side effect of CAR T-cell therapies. Moreover, 4.5% developed immune effector cell-associated neurotoxicity syndrome, an immune response affecting the brain that’s also known to occur with this type of treatment.
In most cases, both of these side effects were considered to be mild or moderate in severity.
A total of 39 Carvykti-treated patients died, 14 due to myeloma progression; 46 deaths were reported among standard care patients, with 30 attributed to disease progression.
Of 10 deaths linked to adverse events in the Carvykti-treated group, seven were due to COVID-19 infections that developed in the first months after the therapy was given, when patients’ immune systems are known to be weakened.
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