# Pleuro-Pulmonary Extramedullary Plasmacytomas in Multiple Myeloma: A 15-Year Experience from a Tertiary Center

## TL;DR

This study examines a rare and aggressive form of multiple myeloma affecting the lungs and pleura, showing poor survival rates and the need for new treatment strategies.

## Contribution

The study presents one of the largest series on pleuro-pulmonary extramedullary plasmacytomas in multiple myeloma, highlighting the need for personalized and novel therapies.

## Key findings

- Pleuro-pulmonary extramedullary disease occurred in 1.6% of multiple myeloma patients, with a median survival of 16 months.
- Most cases (73.5%) developed at relapse, and 25% of patients were alive at 2 years.
- Adverse prognostic markers included elevated β2-microglobulin and LDH, along with specific cytogenetic abnormalities.

## Abstract

Patients with multiple myeloma can develop lesions outside the bone marrow, in the lungs and pleura, a rare but very aggressive form that has been little described so far. We retrospectively analyzed, at a single center, all cases diagnosed between 2010 and 2025 and identified 34 patients with pleuropulmonary involvement. We described how the disease occurs (at onset or relapse), how it manifests (pulmonary infiltrates, pleural involvement, pleural effusion), the diagnostic methods used, and survival. The results show an unfavorable evolution, with a median survival of 16 months and only a quarter of patients alive at 2 years. This study provides one of the largest series published on this topic and emphasizes the need for personalized treatments and modern strategies (e.g., targeted antibodies or modified T cells), providing the basis for future recommendations and clinical trials.

Background/Objectives: Extramedullary involvement in multiple myeloma represents an aggressive disease phenotype, associated with reduced survival and an unfavorable prognosis. Thoracic manifestations are rare and remain poorly characterized in the literature. Methods: We conducted a retrospective, single-center study at the Fundeni Clinical Institute, including patients diagnosed with multiple myeloma between February 2010 and February 2025. The study cohort consisted of 34 patients with infiltration of the pulmonary parenchyma, pleura, or the presence of myelomatous pleural effusion. Diagnosis was confirmed using a combination of imaging modalities (computed tomography or magnetic resonance imaging), cytological examination, immunophenotyping, and histopathological confirmation whenever feasible. Results: Out of a total of 2012 patients with multiple myeloma, the incidence of pleuro-pulmonary extramedullary involvement was 1.6%. The median age at diagnosis was 58 years. Pleuro-pulmonary disease was present at initial diagnosis in 26.5% of cases, while 73.5% developed it at relapse. The most common presentation involved combined pleural involvement and myelomatous effusion (70.6%). Adverse prognostic markers included elevated β2-microglobulin levels (in over 80% of cases) and increased lactate dehydrogenase (LDH) in approximately 50%. Cytogenetic abnormalities such as del(17p), t(4;14), t(14;16), t(11;14), and 1q gain were identified. The median overall survival (OS) from the diagnosis of pleuro-pulmonary extramedullary disease was 16 months, with a 2-year survival rate of 25%. No patient survived beyond 5 years. The median progression-free survival (PFS) was 9 months. Conclusions: Our findings confirm the aggressive clinical course and poor prognosis of these disease manifestations, mainly when they occur at relapse. In the absence of standardized treatment guidelines, individualizing therapy and accessing novel strategies may be essential for improving patient survival.