We report a 51-year-old male with IgA-lambda multiple myeloma who developed severe cutaneous drug eruption following bortezomib treatment. Despite treatment modification to daratumumab-based regimen, the patient achieved complete remission, demonstrating successful management of therapy-related adverse events in CD56-negative myeloma phenotype.

Introduction: Multiple myeloma represents approximately 10% of hematologic malignancies, with CD56-negative variants comprising a rare subset associated with distinct clinical characteristics. Bortezomib-containing regimens remain first-line therapy; however, cutaneous adverse reactions can necessitate treatment modifications. We present a case of successful alternative therapy following severe bortezomib-induced skin toxicity.

Methods/Case Presentation: A 51-year-old male presented with fatigue and back pain. Laboratory investigations revealed IgA elevation (6.8 g/L) with lambda light chain restriction. Serum protein electrophoresis showed decreased albumin (51.6%) and elevated beta fractions. Bone marrow flow cytometry demonstrated plasma cell population: CD38/CD138 100%, CD45 100%, CD117 79.8%, CD56 7.5% (negative), with 96.7% lambda clonality, confirming IgA-lambda multiple myeloma with CD56-negative phenotype.

Staging revealed elevated β2-microglobulin (2.75 mg/L). PET/CT identified metabolically active lytic lesions in T3 vertebra (SUVmax 6.35) and right lumbosacral region (SUVmax 13.41), indicating metabolic progression without hepatosplenomegaly.

Initial treatment commenced with VRD (bortezomib, lenalidomide, dexamethasone). After cycle 1, mild erythematous pruritic rash appeared. Following cycle 2, extensive cutaneous eruptions developed. Skin biopsy revealed upper dermal eosinophil-associated perivascular infiltration with erythrocyte extravasation; direct immunofluorescence was negative, consistent with drug-induced eruption.

Bortezomib was discontinued, and treatment switched to DRd (daratumumab, lenalidomide, dexamethasone). After 2 DRd cycles, M-protein disappeared, serum and urine immunofixation became negative, and hematologic parameters normalized. Follow-up PET/CT showed no active myeloma lesions, confirming complete remission.

Results: The patient achieved biochemical and radiological complete remission within 2 cycles of daratumumab-based therapy following bortezomib-induced severe cutaneous reaction. No significant toxicities were observed with the modified regimen.

Discussion: CD56-negative multiple myeloma represents a rare phenotype with potentially different therapeutic responses. This case demonstrates that severe bortezomib-related cutaneous toxicity can be successfully managed through immediate drug discontinuation and regimen modification. Daratumumab-based therapy proved highly effective, achieving rapid complete remission despite treatment change.

The CD38-targeting monoclonal antibody daratumumab has shown excellent efficacy in both treatment-naive and relapsed myeloma. Our case supports its use as an alternative first-line option when proteasome inhibitor toxicity precludes continued bortezomib therapy.

Early recognition of severe cutaneous drug reactions and prompt treatment modification are crucial for maintaining therapeutic momentum while ensuring patient safety. This case illustrates successful outcomes can be achieved with appropriate alternative regimens in CD56-negative myeloma variants.

Conclusion: CD56-negative IgA-lambda multiple myeloma patients experiencing severe bortezomib-induced cutaneous reactions can achieve excellent outcomes with daratumumab-based alternative therapy. Prompt recognition and management of treatment-related toxicities enables continued effective antimyeloma therapy.