ISATUXIMAB PLUS CARFILZOMIB AND DEXAMETHASONE IN PATIENTS WITH RELAPSED MULTIPLE MYELOMA AND SOFT-TISSUE PLASMACYTOMAS: IKEMA SUBGROUP ANALYSIS
Objectives: Isatuximab (Isa) is an approved IgG1 monoclonal antibody that targets a specific epitope of CD38 and kills multiple myeloma (MM) cells via multiple mechanisms. The Phase 3 IKEMA study (NCT03275285) demonstrated that Isa plus carfilzomib (K) and dexamethasone (d) significantly improved pr...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2021-10-01
|
| Series: | Hematology, Transfusion and Cell Therapy |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2531137921004818 |
| _version_ | 1818723343541469184 |
|---|---|
| author | A Maiolino R Hajek T Jelinek P Moreau T Martin L Pour G Mikala A Symeonidis S Bringhen A Rawlings ML Risse H Vande-Velde I Spicka |
| author_facet | A Maiolino R Hajek T Jelinek P Moreau T Martin L Pour G Mikala A Symeonidis S Bringhen A Rawlings ML Risse H Vande-Velde I Spicka |
| author_sort | A Maiolino |
| collection | DOAJ |
| description | Objectives: Isatuximab (Isa) is an approved IgG1 monoclonal antibody that targets a specific epitope of CD38 and kills multiple myeloma (MM) cells via multiple mechanisms. The Phase 3 IKEMA study (NCT03275285) demonstrated that Isa plus carfilzomib (K) and dexamethasone (d) significantly improved progression-free survival (PFS) compared with Kd in patients (pts) with relapsed MM (hazard ratio [HR], 0.531; 99% CI, 0.32–0.89; p = 0.0007), leading to the approval of Isa-Kd in the US for adults with MM with 1–3 prior lines and in the EU for those with ≥1 prior therapy. The presence of soft-tissue plasmacytomas is associated with poor prognosis, and newer therapies are urgently needed. In this post hoc analysis, we evaluated the efficacy and safety of Isa-Kd vs Kd in pts with relapsed MM and pre-existing soft-tissue plasmacytomas. Material and methods: Pts (n = 302) were randomized (3:2) to Isa-Kd (n = 179) or Kd (n = 123). Isa (10 mg/kg IV) was given weekly for 4 weeks, then every 2 weeks. K (20 mg/m2 days 1–2, then 56 mg/m2) was given twice-weekly 3 of 4 weeks, and d (20 mg) twice-weekly. The independent review committee assessed response based on central radiology review and central lab M-protein using the International Myeloma Working Group criteria. Results: At study entry, 19 (6.3%) pts had soft-tissue plasmacytomas: 12/179 (6.7%) had Isa-Kd and 7/123 (5.7%) had Kd. Overall median (range) duration of exposure in these pts was 41.9 (2–87) weeks for Isa-Kd vs 29.9 (4–83) for Kd, with 41.7% pts still on treatment at cycle 20 in Isa-Kd vs 14.3% pts in Kd. Baseline characteristics in the plasmacytomas subgroup were similar to those in the overall IKEMA intent-to-treat (ITT) population with the exception of ISS stages II (42.1% vs 31.1%) and III (31.6% vs 15.2%), and renal function impairment (38.9% vs 22.1%) which were more prevalent in the plasmacytomas subgroup vs ITT. PFS was improved with Isa-Kd vs Kd: HR, 0.574; 95% CI, 0.125–2.640. Median PFS was 18.76 (95% CI, 4.435–not calculable [NC]) months with Isa-Kd vs NC (0.986–NC) months with Kd. Overall response rate (50.0% vs 28.6%), very good partial response or better (33.3% vs 14.3%), and complete response (25.0% vs 0%, all with minimal residual disease negativity) rates were also improved with Isa-Kd vs Kd. Grade ≥3 TEAE occurred in 12 (100%) pts with Isa-Kd vs 4 (57.1%) with Kd. Grade 5 TEAEs during study treatment occurred in 2 (16.7%) vs 1 (14.3%) pt; serious TEAEs in 9 (75.0%) vs 4 (57.1%); TEAEs leading to discontinuations were 0 (0%) vs 1 (14.3%). Grade 5 events were pneumonia (1 [8.3%], Isa-Kd) and progressive disease (1 [8.3%], Isa-Kd; 1 [14.3%], Kd). Conclusions: In pts with relapsed MM and soft-tissue plasmacytomas, Isa-Kd improved PFS and depth of response compared with Kd alone, with a manageable safety profile, consistent with the benefit observed in the IKEMA study overall population. Isa-Kd is a new treatment option for pts with relapsed MM and soft-tissue plasmacytomas. Funding: Sanofi. |
| first_indexed | 2024-12-17T21:09:01Z |
| format | Article |
| id | doaj.art-d7adb5d9e892452fbd45fe0436ac611e |
| institution | Directory Open Access Journal |
| issn | 2531-1379 |
| language | English |
| last_indexed | 2024-12-17T21:09:01Z |
| publishDate | 2021-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Hematology, Transfusion and Cell Therapy |
| spelling | doaj.art-d7adb5d9e892452fbd45fe0436ac611e2022-12-21T21:32:31ZengElsevierHematology, Transfusion and Cell Therapy2531-13792021-10-0143S197S198ISATUXIMAB PLUS CARFILZOMIB AND DEXAMETHASONE IN PATIENTS WITH RELAPSED MULTIPLE MYELOMA AND SOFT-TISSUE PLASMACYTOMAS: IKEMA SUBGROUP ANALYSISA Maiolino0R Hajek1T Jelinek2P Moreau3T Martin4L Pour5G Mikala6A Symeonidis7S Bringhen8A Rawlings9ML Risse10H Vande-Velde11I Spicka12Department of Internal Medicine, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil; Americas Oncologia, Rio de Janeiro, RJ, BrazilDepartment of Hemato-Oncology, University Hospital Ostrava and University of Ostrava, Ostrava, Czech RepublicDepartment of Hemato-Oncology, University Hospital Ostrava and Faculty of Medicine, University of Ostrava, Ostrava, Czech RepublicDepartment of Hematology, University Hospital Hôtel-Dieu, Nantes, FranceDepartment of Hematology, University of California at San Francisco, San Francisco, United StatesDepartment of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech RepublicNational Institute for Hematology and Infectious Diseases, Department of Hematology and Stem Cell Transplantation, South Pest Central Hospital, Budapest, HungaryHematology Division, Department of Internal Medicine, University of Patras Medical School, Patras, GreeceAzienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Turin, ItalySanofi, Cambridge, United StatesSanofi Research & Development, Vitry-sur-Seine, FranceSanofi, Cambridge, United States1st Department of Medicine – Department of Hematology, 1st Faculty of Medicine, Charles University and General Hospital in Prague, Czech RepublicObjectives: Isatuximab (Isa) is an approved IgG1 monoclonal antibody that targets a specific epitope of CD38 and kills multiple myeloma (MM) cells via multiple mechanisms. The Phase 3 IKEMA study (NCT03275285) demonstrated that Isa plus carfilzomib (K) and dexamethasone (d) significantly improved progression-free survival (PFS) compared with Kd in patients (pts) with relapsed MM (hazard ratio [HR], 0.531; 99% CI, 0.32–0.89; p = 0.0007), leading to the approval of Isa-Kd in the US for adults with MM with 1–3 prior lines and in the EU for those with ≥1 prior therapy. The presence of soft-tissue plasmacytomas is associated with poor prognosis, and newer therapies are urgently needed. In this post hoc analysis, we evaluated the efficacy and safety of Isa-Kd vs Kd in pts with relapsed MM and pre-existing soft-tissue plasmacytomas. Material and methods: Pts (n = 302) were randomized (3:2) to Isa-Kd (n = 179) or Kd (n = 123). Isa (10 mg/kg IV) was given weekly for 4 weeks, then every 2 weeks. K (20 mg/m2 days 1–2, then 56 mg/m2) was given twice-weekly 3 of 4 weeks, and d (20 mg) twice-weekly. The independent review committee assessed response based on central radiology review and central lab M-protein using the International Myeloma Working Group criteria. Results: At study entry, 19 (6.3%) pts had soft-tissue plasmacytomas: 12/179 (6.7%) had Isa-Kd and 7/123 (5.7%) had Kd. Overall median (range) duration of exposure in these pts was 41.9 (2–87) weeks for Isa-Kd vs 29.9 (4–83) for Kd, with 41.7% pts still on treatment at cycle 20 in Isa-Kd vs 14.3% pts in Kd. Baseline characteristics in the plasmacytomas subgroup were similar to those in the overall IKEMA intent-to-treat (ITT) population with the exception of ISS stages II (42.1% vs 31.1%) and III (31.6% vs 15.2%), and renal function impairment (38.9% vs 22.1%) which were more prevalent in the plasmacytomas subgroup vs ITT. PFS was improved with Isa-Kd vs Kd: HR, 0.574; 95% CI, 0.125–2.640. Median PFS was 18.76 (95% CI, 4.435–not calculable [NC]) months with Isa-Kd vs NC (0.986–NC) months with Kd. Overall response rate (50.0% vs 28.6%), very good partial response or better (33.3% vs 14.3%), and complete response (25.0% vs 0%, all with minimal residual disease negativity) rates were also improved with Isa-Kd vs Kd. Grade ≥3 TEAE occurred in 12 (100%) pts with Isa-Kd vs 4 (57.1%) with Kd. Grade 5 TEAEs during study treatment occurred in 2 (16.7%) vs 1 (14.3%) pt; serious TEAEs in 9 (75.0%) vs 4 (57.1%); TEAEs leading to discontinuations were 0 (0%) vs 1 (14.3%). Grade 5 events were pneumonia (1 [8.3%], Isa-Kd) and progressive disease (1 [8.3%], Isa-Kd; 1 [14.3%], Kd). Conclusions: In pts with relapsed MM and soft-tissue plasmacytomas, Isa-Kd improved PFS and depth of response compared with Kd alone, with a manageable safety profile, consistent with the benefit observed in the IKEMA study overall population. Isa-Kd is a new treatment option for pts with relapsed MM and soft-tissue plasmacytomas. Funding: Sanofi.http://www.sciencedirect.com/science/article/pii/S2531137921004818 |
| spellingShingle | A Maiolino R Hajek T Jelinek P Moreau T Martin L Pour G Mikala A Symeonidis S Bringhen A Rawlings ML Risse H Vande-Velde I Spicka ISATUXIMAB PLUS CARFILZOMIB AND DEXAMETHASONE IN PATIENTS WITH RELAPSED MULTIPLE MYELOMA AND SOFT-TISSUE PLASMACYTOMAS: IKEMA SUBGROUP ANALYSIS Hematology, Transfusion and Cell Therapy |
| title | ISATUXIMAB PLUS CARFILZOMIB AND DEXAMETHASONE IN PATIENTS WITH RELAPSED MULTIPLE MYELOMA AND SOFT-TISSUE PLASMACYTOMAS: IKEMA SUBGROUP ANALYSIS |
| title_full | ISATUXIMAB PLUS CARFILZOMIB AND DEXAMETHASONE IN PATIENTS WITH RELAPSED MULTIPLE MYELOMA AND SOFT-TISSUE PLASMACYTOMAS: IKEMA SUBGROUP ANALYSIS |
| title_fullStr | ISATUXIMAB PLUS CARFILZOMIB AND DEXAMETHASONE IN PATIENTS WITH RELAPSED MULTIPLE MYELOMA AND SOFT-TISSUE PLASMACYTOMAS: IKEMA SUBGROUP ANALYSIS |
| title_full_unstemmed | ISATUXIMAB PLUS CARFILZOMIB AND DEXAMETHASONE IN PATIENTS WITH RELAPSED MULTIPLE MYELOMA AND SOFT-TISSUE PLASMACYTOMAS: IKEMA SUBGROUP ANALYSIS |
| title_short | ISATUXIMAB PLUS CARFILZOMIB AND DEXAMETHASONE IN PATIENTS WITH RELAPSED MULTIPLE MYELOMA AND SOFT-TISSUE PLASMACYTOMAS: IKEMA SUBGROUP ANALYSIS |
| title_sort | isatuximab plus carfilzomib and dexamethasone in patients with relapsed multiple myeloma and soft tissue plasmacytomas ikema subgroup analysis |
| url | http://www.sciencedirect.com/science/article/pii/S2531137921004818 |
| work_keys_str_mv | AT amaiolino isatuximabpluscarfilzomibanddexamethasoneinpatientswithrelapsedmultiplemyelomaandsofttissueplasmacytomasikemasubgroupanalysis AT rhajek isatuximabpluscarfilzomibanddexamethasoneinpatientswithrelapsedmultiplemyelomaandsofttissueplasmacytomasikemasubgroupanalysis AT tjelinek isatuximabpluscarfilzomibanddexamethasoneinpatientswithrelapsedmultiplemyelomaandsofttissueplasmacytomasikemasubgroupanalysis AT pmoreau isatuximabpluscarfilzomibanddexamethasoneinpatientswithrelapsedmultiplemyelomaandsofttissueplasmacytomasikemasubgroupanalysis AT tmartin isatuximabpluscarfilzomibanddexamethasoneinpatientswithrelapsedmultiplemyelomaandsofttissueplasmacytomasikemasubgroupanalysis AT lpour isatuximabpluscarfilzomibanddexamethasoneinpatientswithrelapsedmultiplemyelomaandsofttissueplasmacytomasikemasubgroupanalysis AT gmikala isatuximabpluscarfilzomibanddexamethasoneinpatientswithrelapsedmultiplemyelomaandsofttissueplasmacytomasikemasubgroupanalysis AT asymeonidis isatuximabpluscarfilzomibanddexamethasoneinpatientswithrelapsedmultiplemyelomaandsofttissueplasmacytomasikemasubgroupanalysis AT sbringhen isatuximabpluscarfilzomibanddexamethasoneinpatientswithrelapsedmultiplemyelomaandsofttissueplasmacytomasikemasubgroupanalysis AT arawlings isatuximabpluscarfilzomibanddexamethasoneinpatientswithrelapsedmultiplemyelomaandsofttissueplasmacytomasikemasubgroupanalysis AT mlrisse isatuximabpluscarfilzomibanddexamethasoneinpatientswithrelapsedmultiplemyelomaandsofttissueplasmacytomasikemasubgroupanalysis AT hvandevelde isatuximabpluscarfilzomibanddexamethasoneinpatientswithrelapsedmultiplemyelomaandsofttissueplasmacytomasikemasubgroupanalysis AT ispicka isatuximabpluscarfilzomibanddexamethasoneinpatientswithrelapsedmultiplemyelomaandsofttissueplasmacytomasikemasubgroupanalysis |