Relapsed and Refractory Multiple Myeloma with Pleural Involvement: A Case Series
Authors: Peters Douglas , Vardell Victoria A. , Galarza Fortuna Gliceida , Rosqvist Sterling , Wagner Charlotte B , Julian Kelley , Bryan Baylee , Steinbach Mary Nicole , Shewan Samuel , Maxwell Lindsay , McClune Brian , Godara Amandeep , Mohyuddin Ghulam Rehman , Covington Matthew F , Sborov Douglas 
Published: December 2023

Introduction. Development of novel treatments and immunotherapeutics continue to improve outcomes in patients with multiple myeloma (MM), especially in those patients with standard and intermediate risk disease; patients with high-risk disease continue to have dismal outcomes. Secondary extramedullary disease (sEMD) is a high-risk disease feature associated with an expected survival less than one year (Zanwar, AJH, 2023). Detailed description of patients presenting with sEMD involving the pleural has not been previously published. In the present project, we aimed to identify and characterize this patient population.

Methods. This study was approved by the University of Utah (UU) IRB (#00156207). Inclusion was determined by search of the UU Department of Radiology database for all imaging including PET, CT, and MRI; search terms included pleura, pleural, lung, extramedullary, plasmacytoma, and multiple myeloma. Descriptive analysis was completed and included patient demographics, treatment, and outcomes. Survival was described with Kaplan-Meier analysis.

Results. Fourteen patients treated at the UU between 2004 and 2023 were identified as having sEMD and pleural involvement. Demographics are highlighted in Table 1. The median age was 59 (range 34-79), 50% of patients were male, 86% were Caucasian, and 8% were Hispanic. Patients were treated with a median of 2.5 (range 1-9) lines of therapy prior to sEMD development and 6 (range 2-13) in total. 50% of the patients were penta-class refractory. The median follow-up after MM diagnosis was 34.5 months (range 13.0-162.0), median follow-up after pleural EMD diagnosis was 9.0 months (range 0.4-92.0), and the median time to development of pleural EMD following diagnosis was 18.2 months (range 3.8-142.8).

At initial diagnosis, half of the patients had &gt; 50% bone marrow clonal plasma cells, 29% had R-ISS stage 3 disease and 36% had R2-ISS stage III/IV. Of the 11 patients with available cytogenetic information at the time of sEMD diagnosis, 73% had high-risk cytogenetics (defined as presence of del(17p), t(4;14), t(14;16) and/or +1q). The most common cytogenetic abnormalities were +1q in 73%, including 36% with 3 copies and 36% with &gt; 4 copies, amp(1q), and del(17p) in 36% . Of these patients, 18% had double hit and 18% had triple hit disease. The most frequent concomitant cytogenetic abnormalities were +1q and del(17p) seen in 36% of the patients. On imaging, 79% had additional sites of EMD other than the pleura. The most frequent other sites of sEMD were skin/soft tissue, intrabdominal extrahepatic, and hepatic. Pleural effusion was present in only one patient. Following diagnosis of sEMD with pleural involvement, the overall response rate (ORR) was 93% and the ORR was 88% in patients with 1q21 abnormalities. In this population, the median OS from diagnosis was 2.5 years (range 1.1-14) and mOS from diagnosis of pleural EMD was 0.64 years (range 0.03-7.7).

Conclusion. To the best of our knowledge, this is the largest case series focused on the characterization of patients with sEMD and pleural involvement. The survival results align with those recently presented by Zanwar et al., suggesting that pleural involvement does not portend worse prognosis than EMD in general. We highlight that the majority of patients have 1q21 abnormalities and additional sites of EMD. Ultimately, patients with sEMD and pleural involvement have extremely high-risk disease, are responsive to treatments but have a drastically shortened survival.