Expert OpinionOn 6th December 2019, it was announced that the phase II KarMMA study met its primary endpoint of overall response rate (ORR) and key secondary endpoint of complete response (CR) rate. The KarMMA study is investigating idecabtagene vicleucel (ide-cel, also known as bb2121), in patients with relapsed/refractory multiple myeloma (RRMM). Ide-cel is a chimeric antigen receptor (CAR) T-cell therapy targeting B-cell maturation antigen (BCMA).1
The KarMMA study was initiated based on positive results from a phase I, CRB-4012 study of bb2121 in patients with RRMM, summarized by the Multiple Myeloma (MM) Hub here.
KarMMA (NCT03361748)1
- Open-label, single arm, multicenter phase II study in patients with RRMM
- Enrolled; n= 140
- Treated; n= 128
- Patients were treated at target dose between 150 and 450 x 106 CAR T cells
- Patient characteristics:
- Patients had received three or more prior lines of therapy including an immunomodulatory drug (IMiD), a proteasome inhibitor (PI) and an anti-CD38 antibody
- All were refractory to last regimen
- Refractory to anti-CD38: 94%
- Triple refractory: 84%
- Patients had received three or more prior lines of therapy including an immunomodulatory drug (IMiD), a proteasome inhibitor (PI) and an anti-CD38 antibody
- Key efficacy results are shown in Table 1
- The safety results were consistent with the CRB-401 study in 128 evaluable patients
- ≥ Grade III cytokine release syndrome (CRS): 5.5%. One CRS event was fatal
- ≥ Grade III neurotoxicity events: 3.1%. No grade IV events were reported
- Grade III or higher CRS or neurotoxicity at each target dose was <6%
Table 1. Efficacy results from KarMMA
|
CAR T-cell dose |
150 x 106 |
300 x 106 |
450 x 106 |
150 – 450 x 106 |
|
N |
4 |
70 |
54 |
128 |
|
ORR |
50% |
68.6% |
81.5% |
73.4% |
|
CR/stringent CR |
25% |
28.6% |
35.2% |
31.3% |
|
Median duration of response |
- |
9.9 months |
11.3 months |
10.6 months |
|
Median PFS |
- |
5.8 months |
11.3 months |
8.6 months |
More detailed data from this trial are due to be presented at an upcoming medical congress. Meanwhile, several abstracts in the field of CAR T-cell therapy are due to be presented at the 61st American Society of Hematology (ASH) meeting in December 2019.
