EFFICACY AND SAFETY OF ELRANATAMAB IN PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA AND PRIOR B-CELL MATURATION ANTIGEN–DIRECTED THERAPIES: A POOLED ANALYSIS FROM MAGNETISMM STUDIES
Introduction/Objectives: To evaluate the efficacy and safety of elranatamab in a pooled analysis of patients (pts) enrolled in MagnetisMM trials with relapsed or refractory multiple myeloma (RRMM) who had prior exposure to B-cell maturation antigen (BCMA)-directed therapy. Materials and methods: Eli...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-10-01
|
| Series: | Hematology, Transfusion and Cell Therapy |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2531137923009410 |
| _version_ | 1827788462370062336 |
|---|---|
| author | A Nooka A Lesokhin M Mohty R Niesvizky C Maisel B Arnulf S Larson A Varshavsky-Yanovsky X Leleu L Karlin D Vesole N Bahlis CF Larrea N Raje E Leip U Conte M Elmeliegy A Viqueira V Blunk S Manier |
| author_facet | A Nooka A Lesokhin M Mohty R Niesvizky C Maisel B Arnulf S Larson A Varshavsky-Yanovsky X Leleu L Karlin D Vesole N Bahlis CF Larrea N Raje E Leip U Conte M Elmeliegy A Viqueira V Blunk S Manier |
| author_sort | A Nooka |
| collection | DOAJ |
| description | Introduction/Objectives: To evaluate the efficacy and safety of elranatamab in a pooled analysis of patients (pts) enrolled in MagnetisMM trials with relapsed or refractory multiple myeloma (RRMM) who had prior exposure to B-cell maturation antigen (BCMA)-directed therapy. Materials and methods: Eligible pts received at least 1 proteasome inhibitor, 1 immunomodulatory drug, 1 anti-CD38 antibody, and 1 BCMA-directed therapy (antibody-drug conjugate [ADC] and/or chimeric antigen receptor [CAR]-T cells). The pooled analysis included pts in the MagnetisMM-1 trial (NCT03269136; n = 13) who received subcutaneous (SC) elranatamab 215-1000 μg/kg; MM-3 (NCT04649359; n = 64) and MM-9 (NCT05014412; n = 9) who received the recommended phase 2 dose of 76 mg SC once-weekly. Efficacy endpoints were evaluated by investigator per IMWG criteria. TEAEs were graded by CTCAE (MM-1, v4.03; MM-3 & MM-9, v5.0); CRS and ICANS were graded by ASTCT criteria. Results include data up through ≍10 months after last pt initial dose in all pooled studies. Results: In total, 86 pts were included. Median age was 66.0 y (range, 40-84); 47.7% male. At baseline, 69.8% had an ECOG PS ≥1; 24.4% had high risk cytogenetics; 54.7% had extramedullary disease. Pts received a median of 7.0 (3-19) prior lines of therapy, including BCMA-directed ADC (67.4%), CAR T-cells (41.9%); 9.3% received both. 96.5% and 54.7% of pts were triple-class and penta-drug refractory, respectively; among pts who received ADC and CAR-T cells respectively, 79.3% and 27.8% were refractory to ADC and CAR-T cells. After a median follow-up of 10.3 mo (0.3-32.3), median duration of treatment was 3.3 mo (0.03-30.4). At the cut-off date, 24.4% of pts remained on treatment; most common reason for permanent treatment discontinuation was progressive disease (44.2%). The overall response rate (ORR) was 45.3% (95% CI 34.6-56.5), with ≥CR achieved in 17.4% of pts. ORR for pts with prior BCMA-directed ADC and CAR-T cells was 41.4% (95% CI 28.6-55.1) and 52.8% (95% CI 35.5-69.6), respectively. Among responders, median time to objective response was 1.9 mo (0.3-9.3). Median duration of response (DOR) was not reached by 10 mo; the DOR rate at 9 mo was 72.4% (95% CI 54.7-84.2). DOR rate (95% CI) for pts with prior BCMA-directed ADC and CAR-T cells were 67.3% (43.1-83.0) and 78.9% (53.2-91.5) at 9 mo, respectively. Median progression-free survival was 4.8 mo (95% CI 1.9-7.7); median overall survival was not reached by 10 mo, with a rate of 60.1% (95% CI 48.9-69.6) at 9 mo. Most common (≥25% of pts) TEAEs were CRS (65.1% [G3 1.2%]), anemia (59.3% [G3/4, 46.5%]), neutropenia (44.2% [G3/4, 40.7%]), thrombocytopenia (40.7% [G3/4, 29.1%]), diarrhea (33.7% [G3/4, 0%], and lymphopenia (32.6% [G3/4, 30.2%]). 5.8% (G3, 2.3%) of pts. Discussion: In pts with RRMM and prior exposure to BCMA-directed therapies, elranatamab was efficacious and well tolerated; no new safety signals were observed vs the BCMA-naïve population. Conclusions: These results support treatment with elranatamab in pts with RRMM post BCMA-directed therapy. |
| first_indexed | 2024-03-11T17:06:32Z |
| format | Article |
| id | doaj.art-8ebb8a99be494c20a60ee0ecd2fd2319 |
| institution | Directory Open Access Journal |
| issn | 2531-1379 |
| language | English |
| last_indexed | 2024-03-11T17:06:32Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Hematology, Transfusion and Cell Therapy |
| spelling | doaj.art-8ebb8a99be494c20a60ee0ecd2fd23192023-10-20T06:43:32ZengElsevierHematology, Transfusion and Cell Therapy2531-13792023-10-0145S405EFFICACY AND SAFETY OF ELRANATAMAB IN PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA AND PRIOR B-CELL MATURATION ANTIGEN–DIRECTED THERAPIES: A POOLED ANALYSIS FROM MAGNETISMM STUDIESA Nooka0A Lesokhin1M Mohty2R Niesvizky3C Maisel4B Arnulf5S Larson6A Varshavsky-Yanovsky7X Leleu8L Karlin9D Vesole10N Bahlis11CF Larrea12N Raje13E Leip14U Conte15M Elmeliegy16A Viqueira17V Blunk18S Manier19Winship Cancer Institute, Atlanta, United StatesDivision of Hematology and Oncology, Memorial Sloan Kettering Cancer Center/Weill Cornell Medical College, New York, United StatesSorbonne University, Hôpital Saint-Antoine, and INSERM UMRs938, Paris, FranceWeill Cornell Medical College – New York Presbyterian Hospital, New York, United StatesBaylor University Medical Center, Dallas, United StatesHôpital Saint-Louis, Paris, FranceUniversity of California Los Angeles Medical Center, Los Angeles, United StatesFox Chase Cancer Center, Philadelphia, United StatesCentre Hospitalier Universitaire de Poitiers, Poitiers, FranceCentre Hospitalier Lyon, Lyon, FranceJohn Theurer Cancer Center at Hackensack University Medical Center, Hackensack, United StatesArnie Charbonneau Cancer Institute, University of Calgary, Calgary, CanadaHospital Clinic de Barcelona, Barcelona, SpainMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, United StatesPfizer Inc, Cambridge, United StatesPfizer Inc, New York, United StatesPfizer Inc, San Diego, United StatesPfizer SLU, Madrid, SpainPfizer, São Paulo, BrazilLille University Hospital, Lille, FranceIntroduction/Objectives: To evaluate the efficacy and safety of elranatamab in a pooled analysis of patients (pts) enrolled in MagnetisMM trials with relapsed or refractory multiple myeloma (RRMM) who had prior exposure to B-cell maturation antigen (BCMA)-directed therapy. Materials and methods: Eligible pts received at least 1 proteasome inhibitor, 1 immunomodulatory drug, 1 anti-CD38 antibody, and 1 BCMA-directed therapy (antibody-drug conjugate [ADC] and/or chimeric antigen receptor [CAR]-T cells). The pooled analysis included pts in the MagnetisMM-1 trial (NCT03269136; n = 13) who received subcutaneous (SC) elranatamab 215-1000 μg/kg; MM-3 (NCT04649359; n = 64) and MM-9 (NCT05014412; n = 9) who received the recommended phase 2 dose of 76 mg SC once-weekly. Efficacy endpoints were evaluated by investigator per IMWG criteria. TEAEs were graded by CTCAE (MM-1, v4.03; MM-3 & MM-9, v5.0); CRS and ICANS were graded by ASTCT criteria. Results include data up through ≍10 months after last pt initial dose in all pooled studies. Results: In total, 86 pts were included. Median age was 66.0 y (range, 40-84); 47.7% male. At baseline, 69.8% had an ECOG PS ≥1; 24.4% had high risk cytogenetics; 54.7% had extramedullary disease. Pts received a median of 7.0 (3-19) prior lines of therapy, including BCMA-directed ADC (67.4%), CAR T-cells (41.9%); 9.3% received both. 96.5% and 54.7% of pts were triple-class and penta-drug refractory, respectively; among pts who received ADC and CAR-T cells respectively, 79.3% and 27.8% were refractory to ADC and CAR-T cells. After a median follow-up of 10.3 mo (0.3-32.3), median duration of treatment was 3.3 mo (0.03-30.4). At the cut-off date, 24.4% of pts remained on treatment; most common reason for permanent treatment discontinuation was progressive disease (44.2%). The overall response rate (ORR) was 45.3% (95% CI 34.6-56.5), with ≥CR achieved in 17.4% of pts. ORR for pts with prior BCMA-directed ADC and CAR-T cells was 41.4% (95% CI 28.6-55.1) and 52.8% (95% CI 35.5-69.6), respectively. Among responders, median time to objective response was 1.9 mo (0.3-9.3). Median duration of response (DOR) was not reached by 10 mo; the DOR rate at 9 mo was 72.4% (95% CI 54.7-84.2). DOR rate (95% CI) for pts with prior BCMA-directed ADC and CAR-T cells were 67.3% (43.1-83.0) and 78.9% (53.2-91.5) at 9 mo, respectively. Median progression-free survival was 4.8 mo (95% CI 1.9-7.7); median overall survival was not reached by 10 mo, with a rate of 60.1% (95% CI 48.9-69.6) at 9 mo. Most common (≥25% of pts) TEAEs were CRS (65.1% [G3 1.2%]), anemia (59.3% [G3/4, 46.5%]), neutropenia (44.2% [G3/4, 40.7%]), thrombocytopenia (40.7% [G3/4, 29.1%]), diarrhea (33.7% [G3/4, 0%], and lymphopenia (32.6% [G3/4, 30.2%]). 5.8% (G3, 2.3%) of pts. Discussion: In pts with RRMM and prior exposure to BCMA-directed therapies, elranatamab was efficacious and well tolerated; no new safety signals were observed vs the BCMA-naïve population. Conclusions: These results support treatment with elranatamab in pts with RRMM post BCMA-directed therapy.http://www.sciencedirect.com/science/article/pii/S2531137923009410 |
| spellingShingle | A Nooka A Lesokhin M Mohty R Niesvizky C Maisel B Arnulf S Larson A Varshavsky-Yanovsky X Leleu L Karlin D Vesole N Bahlis CF Larrea N Raje E Leip U Conte M Elmeliegy A Viqueira V Blunk S Manier EFFICACY AND SAFETY OF ELRANATAMAB IN PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA AND PRIOR B-CELL MATURATION ANTIGEN–DIRECTED THERAPIES: A POOLED ANALYSIS FROM MAGNETISMM STUDIES Hematology, Transfusion and Cell Therapy |
| title | EFFICACY AND SAFETY OF ELRANATAMAB IN PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA AND PRIOR B-CELL MATURATION ANTIGEN–DIRECTED THERAPIES: A POOLED ANALYSIS FROM MAGNETISMM STUDIES |
| title_full | EFFICACY AND SAFETY OF ELRANATAMAB IN PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA AND PRIOR B-CELL MATURATION ANTIGEN–DIRECTED THERAPIES: A POOLED ANALYSIS FROM MAGNETISMM STUDIES |
| title_fullStr | EFFICACY AND SAFETY OF ELRANATAMAB IN PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA AND PRIOR B-CELL MATURATION ANTIGEN–DIRECTED THERAPIES: A POOLED ANALYSIS FROM MAGNETISMM STUDIES |
| title_full_unstemmed | EFFICACY AND SAFETY OF ELRANATAMAB IN PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA AND PRIOR B-CELL MATURATION ANTIGEN–DIRECTED THERAPIES: A POOLED ANALYSIS FROM MAGNETISMM STUDIES |
| title_short | EFFICACY AND SAFETY OF ELRANATAMAB IN PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA AND PRIOR B-CELL MATURATION ANTIGEN–DIRECTED THERAPIES: A POOLED ANALYSIS FROM MAGNETISMM STUDIES |
| title_sort | efficacy and safety of elranatamab in patients with relapsed or refractory multiple myeloma and prior b cell maturation antigen directed therapies a pooled analysis from magnetismm studies |
| url | http://www.sciencedirect.com/science/article/pii/S2531137923009410 |
| work_keys_str_mv | AT anooka efficacyandsafetyofelranatamabinpatientswithrelapsedorrefractorymultiplemyelomaandpriorbcellmaturationantigendirectedtherapiesapooledanalysisfrommagnetismmstudies AT alesokhin efficacyandsafetyofelranatamabinpatientswithrelapsedorrefractorymultiplemyelomaandpriorbcellmaturationantigendirectedtherapiesapooledanalysisfrommagnetismmstudies AT mmohty efficacyandsafetyofelranatamabinpatientswithrelapsedorrefractorymultiplemyelomaandpriorbcellmaturationantigendirectedtherapiesapooledanalysisfrommagnetismmstudies AT rniesvizky efficacyandsafetyofelranatamabinpatientswithrelapsedorrefractorymultiplemyelomaandpriorbcellmaturationantigendirectedtherapiesapooledanalysisfrommagnetismmstudies AT cmaisel efficacyandsafetyofelranatamabinpatientswithrelapsedorrefractorymultiplemyelomaandpriorbcellmaturationantigendirectedtherapiesapooledanalysisfrommagnetismmstudies AT barnulf efficacyandsafetyofelranatamabinpatientswithrelapsedorrefractorymultiplemyelomaandpriorbcellmaturationantigendirectedtherapiesapooledanalysisfrommagnetismmstudies AT slarson efficacyandsafetyofelranatamabinpatientswithrelapsedorrefractorymultiplemyelomaandpriorbcellmaturationantigendirectedtherapiesapooledanalysisfrommagnetismmstudies AT avarshavskyyanovsky efficacyandsafetyofelranatamabinpatientswithrelapsedorrefractorymultiplemyelomaandpriorbcellmaturationantigendirectedtherapiesapooledanalysisfrommagnetismmstudies AT xleleu efficacyandsafetyofelranatamabinpatientswithrelapsedorrefractorymultiplemyelomaandpriorbcellmaturationantigendirectedtherapiesapooledanalysisfrommagnetismmstudies AT lkarlin efficacyandsafetyofelranatamabinpatientswithrelapsedorrefractorymultiplemyelomaandpriorbcellmaturationantigendirectedtherapiesapooledanalysisfrommagnetismmstudies AT dvesole efficacyandsafetyofelranatamabinpatientswithrelapsedorrefractorymultiplemyelomaandpriorbcellmaturationantigendirectedtherapiesapooledanalysisfrommagnetismmstudies AT nbahlis efficacyandsafetyofelranatamabinpatientswithrelapsedorrefractorymultiplemyelomaandpriorbcellmaturationantigendirectedtherapiesapooledanalysisfrommagnetismmstudies AT cflarrea efficacyandsafetyofelranatamabinpatientswithrelapsedorrefractorymultiplemyelomaandpriorbcellmaturationantigendirectedtherapiesapooledanalysisfrommagnetismmstudies AT nraje efficacyandsafetyofelranatamabinpatientswithrelapsedorrefractorymultiplemyelomaandpriorbcellmaturationantigendirectedtherapiesapooledanalysisfrommagnetismmstudies AT eleip efficacyandsafetyofelranatamabinpatientswithrelapsedorrefractorymultiplemyelomaandpriorbcellmaturationantigendirectedtherapiesapooledanalysisfrommagnetismmstudies AT uconte efficacyandsafetyofelranatamabinpatientswithrelapsedorrefractorymultiplemyelomaandpriorbcellmaturationantigendirectedtherapiesapooledanalysisfrommagnetismmstudies AT melmeliegy efficacyandsafetyofelranatamabinpatientswithrelapsedorrefractorymultiplemyelomaandpriorbcellmaturationantigendirectedtherapiesapooledanalysisfrommagnetismmstudies AT aviqueira efficacyandsafetyofelranatamabinpatientswithrelapsedorrefractorymultiplemyelomaandpriorbcellmaturationantigendirectedtherapiesapooledanalysisfrommagnetismmstudies AT vblunk efficacyandsafetyofelranatamabinpatientswithrelapsedorrefractorymultiplemyelomaandpriorbcellmaturationantigendirectedtherapiesapooledanalysisfrommagnetismmstudies AT smanier efficacyandsafetyofelranatamabinpatientswithrelapsedorrefractorymultiplemyelomaandpriorbcellmaturationantigendirectedtherapiesapooledanalysisfrommagnetismmstudies |