Blenrep shows significant overall survival benefit, reducing the risk of death by 42% in multiple myeloma at or after first relapse – GSK

GSK plc announced statistically significant and clinically meaningful overall survival (OS) results from a planned interim analysis of the DREAMM-7 trial evaluating Blenrep (belantamab mafodotin) in combination with bortezomib plus dexamethasone (BVd) versus daratumumab in combination with bortezomib plus dexamethasone (DVd) as a second line or later treatment for relapsed or refractory multiple myeloma. These data were featured  in an oral presentation at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition. The OS findings from DREAMM-7 build on previous data from the DREAMM-7 and DREAMM-8 trials, which showed a statistically significant and clinically meaningful improvement in progression-free survival (PFS) for both belantamab mafodotin-based combinations versus standard of care comparators.

The belantamab mafodotin combination also resulted in clinically meaningful improvements in all secondary efficacy endpoints including a doubling of complete response rate (stringent complete response plus complete response), minimal residual disease (MRD) negativity rate and median duration of response (DOR). A strong and clinically meaningful overall survival (OS) trend was observed at the interim analysis, with a 43% reduction in the risk of death (HR: 0.57 [95% CI: 0.40-0.80], p-value=0.00049), which has not yet reached the interim criteria for statistical significance of OS. OS follow-up continues and further analyses are planned.

With a median follow up of 39.4 months, the analysis presented today shows a statistically significant 42% reduction in the risk of death among patients receiving the belantamab mafodotin combination (n=243) versus the daratumumab-based comparator (n=251) (HR 0.58; 95% CI: 0.43-0.79; p=0.00023). Although the median overall survival (mOS) was not reached in either arm of the study, the projected mOS for BVd is 84 months compared to 51 months for DVd. The three-year OS rate was 74% in the belantamab mafodotin combination arm and 60% in the daratumumab combination arm.

The belantamab mafodotin combination also showed statistically significant superiority on the key secondary endpoint of minimal residual disease (MRD) negativity (no detectable cancer cells) compared to the daratumumab combination. The greater than 2.5-fold improvement in the rate of MRD negativity seen at the time of the primary analysis for patients who received BVd can now be declared as statistically significant (p<0.00001) after the positive OS readout based on the predefined testing procedure. This further underscores the transformative potential of this belantamab mafodotin combination for multiple myeloma patients at or after their first relapse.

Grade 3 or higher non-ocular adverse events of clinical interest in the belantamab mafodotin combination and daratumumab combination arms, respectively, included thrombocytopenia (55% and 35%; exposure-adjusted event rate: 40 and 29, per 100 person-years), neutropenia (12% and 6%), pneumonia (12% and 4%; exposure-adjusted event rate: 8 and 3, per 100 person-years), and anaemia (8% and 10%).

Eye-related side effects, a known risk of treatment with belantamab mafodotin, were generally reversible, manageable with dose modification, and led to low (9%) treatment discontinuations. Grade 3 or higher ocular adverse events occurred in 34% of patients receiving the belantamab mafodotin combination and primarily included blurred vision (22%), dry eye (7%), eye irritation (5%), and visual impairment (5%). Eighty-two patients (34%) with a best corrected visual acuity (BCVA) score of 20/25 or better in at least one eye at baseline had a worsening in both eyes to 20/50 or worse. Almost all these patients’ events (98%) had resolved at the time of this analysis. The median time to resolution was 22 days. Global health status quality of life (QOL) as measured by the EORTC-QLQ-C30 indicated no difference in global QOL between different treatment arms over time.

Prof. María-Victoria Mateos said ““These results from DREAMM-7 show how belantamab mafodotin in combination with BorDex represents a significant improvement over the daratumumab-based regimen in a second-line multiple myeloma treatment setting. Anti-BCMA therapies are helping to improve outcomes for patients with multiple myeloma, and having an off-the-shelf option, like belantamab mafodotin, that can be administered in a community oncology treatment centre where the majority of patients are treated has the potential to transform the way we treat myeloma at or after first relapse.”

Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK, said: “The compelling overall survival data from the DREAMM-7 trial establish the potential of Blenrep in combination to significantly extend the lives of patients with multiple myeloma at or after first relapse. This represents an important advancement that could redefine the treatment of relapsed or refractory multiple myeloma.”