Legend Biotech Corporation announced that the European Commission (EC) has granted conditional marketing authorization of CARVYKTI® (ciltacabtagene autoleucel; cilta-cel) for the treatment of adults with relapsed and refractory multiple myeloma (RRMM) who have received at least three prior therapies, including a proteasome inhibitor (PI), an immunomodulatory agent (IMiD) and an anti-CD38 antibody, and have demonstrated disease progression on the last therapy. Legend Biotech entered into an exclusive worldwide license and collaboration agreement with Janssen Biotech Inc. (Janssen) to develop and commercialize cilta-cel in December 2017. CARVYKTI® is a chimeric antigen receptor T-cell (CAR-T) therapy featuring two B-cell maturation antigen (BCMA) -targeting single domain antibodies.

CAR-T therapy is specifically developed for each individual patient, and it is administered as a single infusion. This approval was supported by the pivotal CARTITUDE-1 study, including patients who had received a median of six prior treatment regimens (range, 3-18), and had previously received an IMiD, PI and anti-CD38 monoclonal antibody.3 Findings showed that at a median duration of 18 months follow-up (range, 1.5-30.5), a one-time treatment with cilta-cel resulted in deep and durable responses, with 98% (95% confidence interval [CI], 92.7-99.7) of patients with RRMM responding to therapy (98% overall response rate [ORR] (N=97)).3,4 Notably, 80% of the patients achieved stringent complete response (sCR), a measure in which a physician is unable to observe any signs or symptoms of disease via imaging or other tests after treatment. The safety of cilta-cel was evaluated in 179 adult patients across two open-label clinical trials (MMY2001 [1] and MMY2003 [2]).

The most common adverse reactions (=20%) were neutropenia (91%), cytokine release syndrome (CRS) (88%), pyrexia (88%), thrombocytopenia (73%), anemia (72%), leukopenia (54%), lymphopenia (45%), musculoskeletal pain (43%), hypotension (41%), fatigue (40%), transaminase elevation (37%), upper respiratory tract infection (32%), diarrhea (28%), hypocalcemia (27%), hypophosphatemia (26%), nausea (26%), headache (25%), cough (25%), tachycardia (23%), chills (23%), encephalopathy (22%), decreased appetite (22%), oedema (22%), and hypokalemia (20%). As a highly personalized medicine, where a patient's own T-cells are reprogrammed to target and kill cancer cells, administration of CAR-T therapyrequires extensive training, preparation, and certification to ensure the highest quality product and experience for patients.2 Through a phased approach, Legend Biotech's strategic partner, Janssen, will work diligently to activate a limited network of certified treatment centers and will aim to increase availability of cilta-cel across Europe, in an effort to provide oncologists and patients with treatment in a reliable manner.