Outcomes are poor in triple-class exposed patients with relapsed and refractory multiple myeloma ( RRMM ) who progress on immunomodulatory agents ( IMiDs ), proteasome inhibitors ( PIs ), and CD38 antibodies ( mAbs ).
Ide-cel ( Idecabtagene vicleucel ), a BCMA targeted CAR T cell therapy, has shown promising tolerability and efficacy in RRMM patients in the phase I CRB-401 study ( NEJM 2019; 380: 1726 ).
Researchers have presented primary efficacy and safety data from the pivotal phase II KarMMa trial of Ide-cel in relapsed and refractory multiple myeloma.
Enrolled patients had 3 or more prior regimens ( including IMiD, PI, and CD38 mAb ) and were refractory to their last regimen per IMWG criteria.
After lymphodepletion ( Cyclophosphamide 300 mg/m2+ Fludarabine 30 mg/m2 x 3 ), patients received 150─450 × 106 CAR+ T cells ( target dose range ).
Endpoints included overall response rate ( ORR; primary ), complete response ( CR ) rate, duration of response ( DoR ), and progression-free survival ( PFS ).
Of 140 patients enrolled, 128 received Ide-cel. Median age was 61 years; median number of prior regimens was 6; 84% were triple- and 26% were penta-refractory.
Most patients ( 88% ) had bridging therapy.
At data cutoff ( 16 Oct 2019 ), median follow up was 11.3 months.
ORR was 73% and median PFS was 8.6 months; both increased with higher dose.
All subgroups had an ORR greater than or equal to 50%, including older and high-risk patients.
Most common any-grade toxicities were cytopenias ( 97% ) and cytokine release syndrome ( CRS; 84% ).
CRS was mainly grade 1/2; 5 patients ( 5% ) had grade 3, 1 had grade 4, and 1 had grade 5 ( at 300 × 106 ).
Neurotoxicity developed in 23 patients ( 18% ); 4 ( 3% ) grade 3 and 0 grade 4 or more.
Median peak CAR+ T cell expansion occurred at 11 day. Expansion was higher in responders and parameters (A UC0−28d, Cmax ) increased with higher dose, with exposure overlap across doses.
Persistence was durable, with CAR+ T cells detected in 29/49 ( 59% ) and 4/11 patients ( 36% ) at 6 and 12 months.
In conclusion, Ide-cel has demonstrated deep, durable responses in heavily pretreated patients with relapsed and refractory multiple myeloma.
Efficacy and safety have reflected prior reports and have supported a favorable Ide-cel clinical benefit-risk profile across the target dose range. ( Xagena )
Source: American Society of Clinical Oncology ( ASCO ) Virtual Meeting, 2020