Contributions
Abstract: EP1045
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Clinical
Background
Daratumumab has approved indications for the treatment of patients with newly diagnosed multiple myeloma (NDMM) both eligible and ineligible for transplant and treatment of relapsed or refractory multiple myeloma (RRMM).
Aims
To evaluate the efficacy and safety of daratumumab for transplant-ineligible NDMM patients (PICO 1), transplant eligible NDMM patients (PICO 2), and for RRMM patients (PICO 3).
Methods
For each PICO we conduct one Cochrane review according to the standard methodology as outlined in the Cochrane Handbook for Systematic Reviews of Interventions, and assess the certainty in the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Our prioritised outcomes were overall survival, adverse events (CTCAE grade ≥3), serious adverse events, and quality of life.
Results
Transplant-ineligible NDMM (PICO 1): We identified two RCTs (MAIA, ALCYONE) reporting on 1443 patients. Treatment with daratumumab probably increases overall survival (HR 0.67, 95% CI 0.5 to 0.85, I² 39%, moderate-certainty evidence), results in a slight increase of adverse events (grade ≥3) (RR 1.05, 95% CI 1.0 to 1.11, I² 26%, high-certainty evidence) and may increase serious adverse events (RR 1.14, 95% CI 0.86 to 1.51, I² 85%, very low-certainty evidence) compared to treatment without daratumumab. More people receiving daratumumab probably gain at least 10 points of global health status after start of treatment when compared to people receiving no daratumumab (RR 1.13, 95% CI 1.13 to 1.23, I² 0%, moderate-certainty evidence).
Transplant-ineligible NDMM (PICO 2): We identified two RCTs (CASSIOPEIA, GRIFFIN) reporting on 1292 patients. GRIFFIN included 207 patients, but did not report any of our crucial outcomes. Treatment with daratumumab may increase overall survival (HR 0.52, 95% CI 0.33 to 0.82, low-certainty evidence), results in a slight increase of adverse events (grade ≥3) (RR 1.06, 95% CI 1.0 to 1.13, high-certainty evidence) and people may experience less serious adverse events (RR 0.91, 95% CI 0.73 to 1.14, I² 52%, low-certainty evidence) when compared to treatment without daratumumab. More people receiving daratumumab may gain at least 10 points of global health status after start of treatment compared to people receiving no daratumumab (RR 1.07, 95% CI 0.91 to 1.24, low-certainty evidence) at 9.0 months after start of treatment.
RRMM (PICO 3): We identified four RCTs (CANDOR, CASTOR, LEPUS, POLLUX) reporting on 1717 patients. Treatment with daratumumab probably increases overall survival when compared to treatment without daratumumab (HR 0.62, 95% CI 0.49 to 0.79, I² 7%, moderate-certainty evidence). Two studies reported safety outcomes for 1044 patients. Treatment with daratumumab probably results in a slight increase of adverse events (grade ≥3) (RR 1.17, 95% CI 1.04 to 1.31, I² 64%, moderate-certainty evidence) and probably increases serious adverse events when compared to treatment without daratumumab (RR 1.21, 95% CI 1.09 to 1.35, I² 0%, moderate-certainty evidence). More people receiving daratumumab may gain at least 10 points of global health status after start of treatment compared to people receiving no daratumumab (RR 1.07, 95% CI 1.07 to 1.22, I² 0%, low-certainty evidence) at 9 months after start of treatment.
Conclusion
Treatment with daratumumab is likely to retrieve gain in survival, but increases the risk of grade ≥3 and serious adverse events and may contribute to a clinically important improvement of quality of life compared to treatment without daratumumab.
Keyword(s): Multiple myeloma, Systematic review
Abstract: EP1045
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Clinical
Background
Daratumumab has approved indications for the treatment of patients with newly diagnosed multiple myeloma (NDMM) both eligible and ineligible for transplant and treatment of relapsed or refractory multiple myeloma (RRMM).
Aims
To evaluate the efficacy and safety of daratumumab for transplant-ineligible NDMM patients (PICO 1), transplant eligible NDMM patients (PICO 2), and for RRMM patients (PICO 3).
Methods
For each PICO we conduct one Cochrane review according to the standard methodology as outlined in the Cochrane Handbook for Systematic Reviews of Interventions, and assess the certainty in the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Our prioritised outcomes were overall survival, adverse events (CTCAE grade ≥3), serious adverse events, and quality of life.
Results
Transplant-ineligible NDMM (PICO 1): We identified two RCTs (MAIA, ALCYONE) reporting on 1443 patients. Treatment with daratumumab probably increases overall survival (HR 0.67, 95% CI 0.5 to 0.85, I² 39%, moderate-certainty evidence), results in a slight increase of adverse events (grade ≥3) (RR 1.05, 95% CI 1.0 to 1.11, I² 26%, high-certainty evidence) and may increase serious adverse events (RR 1.14, 95% CI 0.86 to 1.51, I² 85%, very low-certainty evidence) compared to treatment without daratumumab. More people receiving daratumumab probably gain at least 10 points of global health status after start of treatment when compared to people receiving no daratumumab (RR 1.13, 95% CI 1.13 to 1.23, I² 0%, moderate-certainty evidence).
Transplant-ineligible NDMM (PICO 2): We identified two RCTs (CASSIOPEIA, GRIFFIN) reporting on 1292 patients. GRIFFIN included 207 patients, but did not report any of our crucial outcomes. Treatment with daratumumab may increase overall survival (HR 0.52, 95% CI 0.33 to 0.82, low-certainty evidence), results in a slight increase of adverse events (grade ≥3) (RR 1.06, 95% CI 1.0 to 1.13, high-certainty evidence) and people may experience less serious adverse events (RR 0.91, 95% CI 0.73 to 1.14, I² 52%, low-certainty evidence) when compared to treatment without daratumumab. More people receiving daratumumab may gain at least 10 points of global health status after start of treatment compared to people receiving no daratumumab (RR 1.07, 95% CI 0.91 to 1.24, low-certainty evidence) at 9.0 months after start of treatment.
RRMM (PICO 3): We identified four RCTs (CANDOR, CASTOR, LEPUS, POLLUX) reporting on 1717 patients. Treatment with daratumumab probably increases overall survival when compared to treatment without daratumumab (HR 0.62, 95% CI 0.49 to 0.79, I² 7%, moderate-certainty evidence). Two studies reported safety outcomes for 1044 patients. Treatment with daratumumab probably results in a slight increase of adverse events (grade ≥3) (RR 1.17, 95% CI 1.04 to 1.31, I² 64%, moderate-certainty evidence) and probably increases serious adverse events when compared to treatment without daratumumab (RR 1.21, 95% CI 1.09 to 1.35, I² 0%, moderate-certainty evidence). More people receiving daratumumab may gain at least 10 points of global health status after start of treatment compared to people receiving no daratumumab (RR 1.07, 95% CI 1.07 to 1.22, I² 0%, low-certainty evidence) at 9 months after start of treatment.
Conclusion
Treatment with daratumumab is likely to retrieve gain in survival, but increases the risk of grade ≥3 and serious adverse events and may contribute to a clinically important improvement of quality of life compared to treatment without daratumumab.
Keyword(s): Multiple myeloma, Systematic review