At the virtual 2021 annual American Society of Clinical Oncology conference (ASCO 2021) on June 4–8, Johnson & Johnson (J&J) presented updated results from its Phase I/II study CARTITUDE-1 in relapsed/refractory (R/R) multiple myeloma (MM). J&J’s anti-BCMA CAR-T cell product ciltacabtagene autoleucel (cilta-cel) was infused in R/R patients who had received more than three prior regimens, with overall response rate (ORR) as the primary endpoint.
R/R MM patients have several options with different mechanisms of action (MOAs) available, including but not limited to Bristol-Myers Squibbs’ (BMS) Empliciti (elotuzumab), GlaxoSmithKline’s Blenrep (belantamab mafodotin), Karyopharm Therapeutics’ Xpovio (Selinexor), and Oncopeptides’ Pepaxto (melfuflen). The only authorized CAR-T product yet is Bluebird Bio/BMS’ Abecma (idecabtagene vicleucel), available for patients in the fifth line of therapy onwards in the US.
In the CARTITUDE-1 study, patients treated with cilta-cel who received a median of six previous lines of treatment, displayed an ORR of 98%, with 80% of responses being stringent complete responses (CRs). The 18-month progression-free survival and overall survival were 66% and 81% respectively. Cytokine release syndrome (CRS), a common adverse event (AE) of CAR-T cells, occurred in 95% of patients, only 4% of which was Grade 3 or 4. Neurotoxicity appeared in 21% of patients, and 10% of patients had neurotoxicity grade ≥3. Abecma was FDA approved in March 2021 on the basis of a 72% ORR seen in the KarMMa trial with. Thus, cilta-cel’s efficacy compares at least favorably to Abecma’s, but AEs and duration of response will play a key role in determining the dominant product. Cilta-cel’s stringent CR % is impressive, however, and is likely to greatly influence uptake.
A rolling submission to the FDA was initiated in December 2020 and a submission to the EMA in April 2021. With priority review granted in the US, an FDA decision will have been made by December 2021 and an EMA decision is likely in Q1, 2022 with accelerated assessment in place. Therefore, Abecma’s first-to-market advantage will only be a few months, allowing cilta-cel to compete based on updated clinical data. In the early days of CAR-T cells in MM, no one product is expected to become the gold standard and there will be plenty of room for competition. GlobalData forecasts both Abecma and cilta-cel to become blockbusters, each reaching $2.6B in global sales by 2027.