Delayed Evolution: A Rare Case of Multiple Myeloma Emerging Two Decades After Initial Diagnosis of Amyloidosis

Introduction/Background/Significance: Primary light chain (AL) amyloidosis and multiple myeloma (MM) are both clonal plasma cell disorders. AL amyloidosis and MM are distinguished primarily by their pathophysiology and clinical manifestations. MM is characterized by uncontrolled plasma cell proliferation and overproduction of monoclonal proteins, leading to end-organ damage. In AL amyloidosis, misfolded light chains form amyloid fibrils that deposit in organs, causing dysfunction. Approximately 10–15% of patients with MM develop concurrent AL amyloidosis. However, the progression from AL amyloidosis to multiple myeloma is rare. We report a case in which a patient developed multiple myeloma more than twenty years after an initial diagnosis of amyloidosis.

Materials and Methods/Case Presentation/Objective: A 64-year-old male with remote history of AL amyloidosis status post autologous stem cell transplant (ASCT) 24 years prior presented with worsening fatigue and renal function. His creatinine increased more than three-fold from his previously noted baseline. Prior to this encounter, he was medically doing well for years and not on maintenance therapy while in remission. Workup revealed a hemoglobin of 8.5 g/dL, bone marrow (BM) biopsy with hypercellular marrow (60%) with 50% involvement of plasma cells, predominantly lambda. Serum protein electrophoresis identified elevated lambda M protein of 0.2 g/dL. Myeloma FISH panel was negative. PET-CT showed numerous lytic lesions of the spine and pelvis. These findings contributed to the diagnosis of MM and the patient initially started induction chemotherapy with daratumumab, lenalidomide, bortezomib, and dexamethasone (Dara-RVD). He was later transitioned to daratumumab, cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) due to worsening renal function, completing six total cycles. Post induction BM biopsy showed a marked reduction in plasma cells (5–7%), though PET-CT continued to show multiple lytic lesions throughout the spine and pelvis. He subsequently underwent a second ASCT and has done well thus far along with improved kidney function.

Results/Description/Main Outcome Measures: Progression from AL amyloidosis to MM is exceedingly rare and has been only infrequently documented in the literature. In a case series by Rajkumar et al., six patients progressed from AL amyloidosis to MM within 10 to 81 months of the initial diagnosis. Our case is notable for its unprecedented interval, with the patient developing MM more than two decades after the initial diagnosis of AL amyloidosis. Patients in remission from AL amyloidosis are not typically monitored for MM-specific features, especially not many years after initial diagnosis. Rajkumar et al. proposed this rare pattern of progression highlights the notion that AL amyloidosis and MM represent points along a spectrum of clonal plasma cell disorders. Given the potential for bidirectional progression, these findings highlight the importance of considering long-term surveillance in patients with AL amyloidosis, especially those in sustained remission, to detect late transformation to multiple myeloma.

Conclusions: This case represents an unprecedented timeline for progression from AL amyloidosis to MM and emphasizes the need to reconsider long-term surveillance strategies in patients with sustained remission from AL amyloidosis to enable early detection of late disease transformation.

References

Rajkumar SV, Gertz MA, Kyle RA. Primary systemic amyloidosis with delayed progression to multiple myeloma. Cancer. 1998 Apr 15;82(8):1501-5. PMID: 9554527.