Multiple myeloma (MM) in young adults is uncommon, and high-risk cytogenetics complicate standard pathways. We report a 31-year-old woman with IgA-κ MM, large sacral involvement, and adverse genetics, achieving a deep remission with daratumumab–lenalidomide–dexamethasone (DRd) plus focal radiotherapy (RT), electing to defer autologous transplant.

Single-patient case review from prospectively maintained records. Data included presenting features, MRI/PET-CT, serum/urine monoclonal studies, bone-marrow histology/flow, and plasma-cell FISH. Treatment, response, and tolerability were documented.

A previously healthy 31-year-old presented with severe nocturnal lumbosacral pain and right-sciatic radiation. MRI revealed a left-lateral sacral mass (77 × 56 mm) with contrast enhancement; PET-CT demonstrated focal hypermetabolic lytic lesions in sacrum, L1, pubis, and scapula (SUVmax 5.4–5.9), with no visceral/extramedullary organ disease. Serum studies showed an IgA-κ M-component with elevated free light-chain ratio; β2-microglobulin was 4.2 mg/L (ISS stage II). Bone-marrow biopsy displayed intertrabecular plasma-cell infiltration; immunophenotype CD38+, CD56+, κ-restricted, CD19–; reticulin 0–1/4; amyloid negative. Plasma-cell FISH identified t(14;20)(IGH–MAFB) in ∼35% of cells, indicating high-risk disease.

She commenced DRd and received concurrent local RT to the sacrum (fractionated) for rapid pain control. Treatment was well tolerated, without renal or calcium derangements. Clinically, pain resolved; biochemically, the M-component cleared; radiologically, bone foci regressed with disappearance of pathologic uptake on interval imaging. Bone-marrow reassessment showed marked reduction of clonal plasma cells, consistent with deep response. Given age, recovery, and patient preference, autologous transplant was performed; she continued maintenance (daratumumab ± lenalidomide) with sustained remission on follow-up.

This case underscores four practice points. (1) Aggressive osseous disease at young age can herald high-risk biology; early, integrated MRI/PET staging captures true burden and guides focal RT for symptom control while systemic therapy acts on disseminated marrow disease. (2) Immunophenotype and marrow context (CD38+/CD56+, κ-restriction; low reticulin) affirmed clonal plasmacytosis consistent with MM rather than solitary plasmacytoma or IgG4-related processes. (3) Cytogenetic risk—notably t(14;20)—supports intensified monoclonal-antibody–based induction (DRd) and vigilant surveillance, as this lesion associates with inferior outcomes on IMiD/PI-only backbones. (4) In select young patients achieving deep remission, deferring ASCT after robust daratumumab-based induction and consolidative RT can be reasonable when aligned with patient values and close monitoring—especially if toxicity, fertility considerations, or personal preference weigh heavily.

Young-onset, high-risk IgA-κ MM with a large sacral mass achieved a durable, deep remission on DRd plus focal RT, permitting ASCT deferral with maintenance therapy and sustained disease control. Pairing comprehensive imaging with cytogenetic risk and early antibody-based induction may optimize outcomes in comparable high-risk, bone-predominant presentations.