The combination of dexamethasone with isatuximab was associated with increased responses and improvements in survival compared with isatuximab monotherapy in patients with relapsed/refractory multiple myeloma, according to results from a randomized phase II study. Findings from this study suggest dexamethasone, which is frequently used as a syndergistic treatment for multidrug regimens, could provide additional immunomodulatory effects to those already observed with monoclonal antibodies.
In this study, which was published in Blood, researchers assessed the efficacy of either isatuximab 20 mg/kg once weekly, followed by cycles of once every 2 weeks, as monotherapy (n=109) or isatuximab combined with dexamethasone 40 mg/day once weekly (n=55). Patients ≥75 years of age received dexamethasone at 20 mg/day once weekly in combination with isatuximab.
In both arms, the median number of prior lines of therapy was four. The duration of treatment exposure in the isatuximab and isatuximab plus dexamethasone groups was 18.9 weeks and 30.0 weeks, respectively.
Patients in the isatuximab monotherapy arm had a significantly lower overall response rate (ORR; 23.9% vs. 43.6%; odds ratio [OR] = 0.405; p=0.008). This included:
- partial response rates of 14.7% for isatuximab monotherapy vs. 23.6% for isatuximab-dexamethasone
- very good partial response rates of 9.2% for isatuximab vs. 20.0% for isatuximab-dexamethasone
No patients in this study achieved complete response (CR), the investigators noted, “however, the true CR rate may be underestimated because of isatuximab interference with M protein measurement.” They also reported an overall clinical benefit response rate (defined as patients who achieved at least a minimal response) of 43.1% in the isatuximab-only group and 54.5% in the combination group.
Adding dexamethasone to isatuximab treatment also was associated with longer median progression-free survival (PFS): 10.2 months for combination vs. 4.9 months for monotherapy (hazard ratio [HR] = 0.677; p<0.04). However, there was no significant difference in median overall survival (OS) between the groups (18.9 months for isatuximab only vs. 17.3 months for isatuximab-dexamethasone; HR=0.799; p=0.19). One-year OS rates were 63.5% and 73.8% for the monotherapy and combination groups, respectively.
Findings from this study suggest dexamethasone, which is frequently used as a syndergistic treatment for multidrug regimens, could provide additional immunomodulatory effects.
“Addition of dexamethasone to isatuximab resulted in moderate steroid-related toxicity that was manageable, did not change the incidence of infusion reactions or high-grade infections, and resulted in a similar number of serious adverse events (AEs) and discontinuations due to AEs or fatal AEs,” the researchers wrote. Nearly all patients in the monotherapy and dual-therapy groups experienced at least one treatment-emergent AE (91.7% and 92.7%, respectively) during the study period. The most common AEs in the overall population were hematologic abnormalities; infusion reactions; and respiratory, thoracic, and mediastinal disorders (TABLE).
According to the study authors, the analysis for the primary endpoint of response rates was not powered for comparison between the treatment groups. In spite of this lack of power, the researchers emphasized the importance of the significant increase in ORR and PFS in the isatuximab plus dexamethasone group relative to the isatuximab-only arm.
Study authors report relationships with Sanofi Genzyme, which sponsored this trial.
Dimopoulos MA, Bringhen S, Anttila P, et al. Isatuximab as monotherapy and combined with dexamethasone in patients with relapsed/refractory multiple myeloma. Blood. 2020 October 20. [Epub ahead of print]