Contributions
Abstract: EP962
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Clinical
Background
The dual CAR-T GC012F - developed on the novel FasT CAR-T platform, targeting both B cell maturation antigen (BCMA) and CD19, was designed to improve depth of response and overall efficacy for CAR-T as therapy for Multiple Myeloma.
Aims
Here we present updated data for the single-arm multicenter phase 1 study (NCT04236011; NCT04182581) including additional pts treated.
Methods
From October 2019 to July 2020, 19 heavily pretreated Relapsed/Refractory Multiple Myeloma (RRMM) pts (age 27-71) with a median of 5 prior lines (range 2-9) received a single infusion of GC012F. 94.7% (18/19) were high risk (HR; defined by mSMART), 5 pts had extramedullary disease, 1 pt presented with plasma cell leukemia, and 15/19 were refractory to last therapy. 4/19 pts had received prior anti-CD38, 18/19 pts prior IMiD. 18/19 pts were refractory to PI, 17 pts to IMiD, 3 pts being primary refractory. After lymphodepletion over 2-3 days (30 mg/m2/d, 300mg/ m2/d Flu/Cy) CAR-T cells were administered as single infusion at 3 dose levels:1x105/kg (DL1) n=1, 2x105/kg (DL2) n=9 and 3x105/kg (DL3) n=9.
Results
As of Jan 12th 2021 cut-off, 19 pts were evaluated for response. Overall response rate (ORR) was 94.7% - all responses were VGPR or better (94.7% - 16/18 sCR, 2/18 VGPR) with all pts (19/19) being Minimal Residual Disease negative (MRD-) by flow cytometry (10-4;10-6) - earliest response d28 post infusion. 100% of pts achieved a reduction of paraprotein, 18/19 a 100% reduction. Best response was MRD-sCR in 16/19 pts (84.2%). In DL3 (n=9) 4 additional pts were response evaluable for 6 mth follow-up: 100% (9/9) of pts achieved MRD-sCR as best response, 87.5% (7/8) of response evaluable pts maintained MRD-sCR at a landmark analysis at 6 mths. At data cut off, the median time to follow up was 13.8 mths (6.1-16.4) – with the median duration of response not yet reached. Cytokine Release Syndrome (CRS) and ICANs were graded by ASBMTcriteria: grade 1-2 n=16 (84.2%), grade 3 n=2 (10.5%). Median duration of CRS was 4d (1-8d). No grade 4/5 CRS or Immunce effector cell-associated Neurotoxicity syndrome (ICANS) were observed. 2 deaths occurred on study and were assessed as not related to therapy – one reported previously; one patient was diagnosed with&
Conclusion
BCMA-CD19 dual FasT CAR-T GC012F showed early, deep and durable responses with a high ORR (94.7%; VGPR or better) including a high MRD negative sCR rate (DL3=100%, n=9) in high risk RRMM pts including those refractory to anti-CD38, PI and IMIDs with a favorable safety profile consistent with previous findings. BCMA-CD19 dual FasT CAR-T GC012F may present a new treatment approach for patients with RRMM including those with high-risk features refractory to standard of care.
Abstract: EP962
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Clinical
Background
The dual CAR-T GC012F - developed on the novel FasT CAR-T platform, targeting both B cell maturation antigen (BCMA) and CD19, was designed to improve depth of response and overall efficacy for CAR-T as therapy for Multiple Myeloma.
Aims
Here we present updated data for the single-arm multicenter phase 1 study (NCT04236011; NCT04182581) including additional pts treated.
Methods
From October 2019 to July 2020, 19 heavily pretreated Relapsed/Refractory Multiple Myeloma (RRMM) pts (age 27-71) with a median of 5 prior lines (range 2-9) received a single infusion of GC012F. 94.7% (18/19) were high risk (HR; defined by mSMART), 5 pts had extramedullary disease, 1 pt presented with plasma cell leukemia, and 15/19 were refractory to last therapy. 4/19 pts had received prior anti-CD38, 18/19 pts prior IMiD. 18/19 pts were refractory to PI, 17 pts to IMiD, 3 pts being primary refractory. After lymphodepletion over 2-3 days (30 mg/m2/d, 300mg/ m2/d Flu/Cy) CAR-T cells were administered as single infusion at 3 dose levels:1x105/kg (DL1) n=1, 2x105/kg (DL2) n=9 and 3x105/kg (DL3) n=9.
Results
As of Jan 12th 2021 cut-off, 19 pts were evaluated for response. Overall response rate (ORR) was 94.7% - all responses were VGPR or better (94.7% - 16/18 sCR, 2/18 VGPR) with all pts (19/19) being Minimal Residual Disease negative (MRD-) by flow cytometry (10-4;10-6) - earliest response d28 post infusion. 100% of pts achieved a reduction of paraprotein, 18/19 a 100% reduction. Best response was MRD-sCR in 16/19 pts (84.2%). In DL3 (n=9) 4 additional pts were response evaluable for 6 mth follow-up: 100% (9/9) of pts achieved MRD-sCR as best response, 87.5% (7/8) of response evaluable pts maintained MRD-sCR at a landmark analysis at 6 mths. At data cut off, the median time to follow up was 13.8 mths (6.1-16.4) – with the median duration of response not yet reached. Cytokine Release Syndrome (CRS) and ICANs were graded by ASBMTcriteria: grade 1-2 n=16 (84.2%), grade 3 n=2 (10.5%). Median duration of CRS was 4d (1-8d). No grade 4/5 CRS or Immunce effector cell-associated Neurotoxicity syndrome (ICANS) were observed. 2 deaths occurred on study and were assessed as not related to therapy – one reported previously; one patient was diagnosed with&
Conclusion
BCMA-CD19 dual FasT CAR-T GC012F showed early, deep and durable responses with a high ORR (94.7%; VGPR or better) including a high MRD negative sCR rate (DL3=100%, n=9) in high risk RRMM pts including those refractory to anti-CD38, PI and IMIDs with a favorable safety profile consistent with previous findings. BCMA-CD19 dual FasT CAR-T GC012F may present a new treatment approach for patients with RRMM including those with high-risk features refractory to standard of care.