Evaluation of Immune Reconstitution in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) Treated with Cevostamab in Phase I Study GO39775
Results: At data cut-off (March 1, 2023), a total of 310 patients were enrolled in GO39775. 76 patients met the inclusion criteria and were eligible for analysis. Median age was 65 years (range: 43–82), with a median of 6 previous lines of therapy (range: 2–12). 46 patients (60.5%) had IgG isotype, 10 (13.2%) had IgA isotype, and 20 (26.3%) had light chain disease.
Of the 76 patients who met the inclusion criteria, 10 (13.2%) experienced IR (see Table); 5 patients had IgG isotype, 3 had IgA isotype, and 2 had light chain disease. The 10 patients with IR were treated for a median of 323 days (range: 64–364). Of these, 6 patients had IR at a median time of Day 156 (range: 123–260) while on cevostamab, while 4 patients had IR at a median time of Day 242 (range: 133–309) after stopping cevostamab. Of the 6 patients who reconstituted on cevostamab, 1 had IgG isotype, 3 had IgA isotype, and 2 had light chain disease. All 4 patients who reconstituted after stopping cevostamab had IgG isotype. Apart from disease isotype, no other baseline characteristic demonstrated a trend with IR.
Discussion: The majority of patients with a response to cevostamab in the GO39775 study had baseline IP, consistent with previous findings in RRMM. Among eligible responders, 10 patients (13.2%) reconstituted ≥1 polyclonal Ig, highlighting that disease control may allow some patients to reverse IP. Of the patients who had IR, 6 had immune recovery while on cevostamab therapy, which indicates that IR is possible on cevostamab once disease control is achieved. Our findings demonstrate that despite normal plasma cell targeting, IR can occur while receiving a FcRH5xCD3 bispecific antibody. Further analysis on a larger patient pool may provide more insight into the characteristics of patients with RRMM who experience IR on cevostamab therapy.