Case Presentation: Extramedullary Progression After CAR-T Therapy in High-Risk Multiple Myeloma
Patient Case:
A 52-year-old patient with high-risk IgA lambda multiple myeloma who was initially diagnosed with smoldering multiple myeloma in 2015 presented in 2017 with increasing infections, immunoparesis, and a rising M spike.
At initial diagnosis, there were no CRAB features. Serum protein electrophoresis (SPEP) demonstrated an M-spike of 2.82 g/dL, with kappa 1.01 mg/L, lambda 160.00 mg/L, and a kappa/lambda ratio of 0.06. Bone marrow biopsy revealed 15 to 20% monoclonal plasma cells. Cytogenetic analysis showed 1q21 gain (92.5%) and t(4;14) translocation (97%), with an otherwise normal karyotype. No lytic bone disease was identified, and the disease was staged as R-ISS stage II.
The patient subsequently underwent multiple lines of therapy including:
- VRd induction followed by autologous stem cell transplant (autoSCT #1; melphalan 200 mg/m², 2017), achieving stringent complete response (sCR), minimal residual disease (MRD)–positive. Lenalidomide maintenance was discontinued due to intolerance.
- Disease progression in 2020 led to initiation of KRd, followed by a second autologous transplant (autoSCT #2), achieving very good partial response and MRD negativity by flow cytometry. KPd consolidation was administered, followed by pomalidomide monotherapy, which was discontinued in 2021 due to intolerance.
- Progression in April 2023 prompted initiation of daratumumab, pomalidomide, and dexamethasone; pomalidomide was again not tolerated, and the patient continued on daratumumab monotherapy. With subsequent biochemical progression, the patient underwent leukapheresis for CAR T-cell therapy with pomalidomide bridging.
- The patient received ciltacabtagene autoleucel (Carvykti) on December 4, 2023, achieving sCR at 6 months post–CAR-T. Disease progression occurred in June 2025, characterized by significant extramedullary disease (EMD).
- Talquetamab was initiated for widespread extramedullary disease and rising lambda free light chains (>220 mg/L).
Imaging findings included a PET/CT in April 2023 demonstrating multiple hypermetabolic osseous lesions involving the ribs, vertebrae, pelvis, and left humerus (largest measuring 11 cm). MRI on October 23, 2023, revealed a T9 compression fracture and rib lesion; palliative radiation therapy (2000 cGy in 5 fractions) was delivered. PET/CT in July 2025 showed widespread extramedullary disease and new osseous lesions correlating with rising light chains. Notably, the last two progression events were marked by increasing bony disease and EMD.
Comorbidities include anxiety, anemia, peripheral neuropathy, depression, recurrent urinary tract infections, and a left iliac/common iliac vein deep vein thrombosis (August 2023), for which the patient remains on rivaroxaban.
Given progression after CAR-T therapy and high-risk disease features, talquetamab was initiated. At 1-month assessment, PET/CT demonstrated interval improvement, and serum free light chains normalized, indicating an early response.
Treatment-related toxicity has included a grade 2 dermatologic reaction characterized by a blistering rash on the feet, which developed shortly after step-up dosing. Supportive management has been initiated, with ongoing monitoring and consideration of dose modification based on tolerability.
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