Rapid regression of a bulky cranial lesion in high-risk multiple myeloma with isatuximab-based quadruplet induction

A 77-year-old woman with newly diagnosed immunoglobulin (Ig)G-κ multiple myeloma presented with a massive cranial paraskeletal (PS) lesion (84 × 59 × 62 mm) compressing the occipital lobe. Fluorescence in situ hybridization of bone marrow aspirate revealed 1q21 gain and 17p deletion. Induction therapy with isatuximab, bortezomib, lenalidomide, and dexamethasone (Isa-VRd) was initiated to avoid emergent local intervention. The response was rapid; head computed tomography on day 28 showed an approximately 80% reduction in bidimensional measurements, with near-complete radiologic resolution by the end of the second cycle. After the third cycle, elective reconstructive cranioplasty was performed. Although a pretreatment biopsy was not feasible, the resected tissue showed no detectable plasma cells. Measurable residual disease in the bone marrow was negative (< 10^-5) after the fourth cycle. Exploratory longitudinal flow cytometry of the peripheral blood revealed baseline expansion of CD8-positive terminally differentiated effector memory re-expressing CD45RA (TEMRA) cells and persistent TEMRA subset dominance after the fourth cycle. This case suggests that upfront anti-CD38 antibody-containing quadruplet therapy can enable deferral of urgent local intervention through rapid cytoreduction in select patients with bulky cranial PS involvement, even in older adults with high-risk cytogenetic features and compromised immune profiles.