Abstract
Published experience with carfilzomib in patients with relapsed/refractory multiple myeloma (RRMM) and extramedullary disease (EMD) is still limited. The current study aimed to assess the efficacy and safety of carfilzomib containing therapy regimens in EMD. We retrospectively analyzed 45 patients with extramedullary RRMM treated with carfilzomib from June 2013 to September 2019. The median age at the start of carfilzomib was 64 (range 40–80) years. Twenty (44%) and 25 (56%) patients had paraosseous manifestation and EMD without adjacency to bone, respectively. The serological overall response rate (ORR) was 59%. Extramedullary response was evaluable in 33 patients, nine (27%) of them achieved partial remission (PR) (ORR = 27%). In 15 (33%) patients, we observed no extramedullary response despite serological response. The median progression-free survival (PFS) and overall survival (OS) were five (95% CI, 3.5–6.5) and ten (95% CI, 7.5–12.5) months, respectively. EMD without adjacency to bone was associated with a significantly inferior PFS (p = 0.004) and OS (p = 0.04) compared to paraosseous lesions. Carfilzomib based treatment strategies showed some efficacy in heavily pretreated patients with extramedullary RRMM but could not overcome the negative prognostic value of EMD. Due to the discrepancy between serological and extramedullary response, evaluation of extramedullary response using imaging is mandatory in these patients.
Highlights
In multiple myeloma (MM), tumor growth is usually strongly dependent on the bone marrow microenvironment [1]
We identified patients with extramedullary refractory multiple myeloma (RRMM) treated with carfilzomib-based regimens from June 2013 to September
The diagnosis of extramedullary disease (EMD) was based on the histology of tumor bulk or, if biopsy was not possible, on imaging using computed tomography (CT), diffusion weighted magnetic resonance imaging (MRI), or positron emission tomography (PET)
Summary
In multiple myeloma (MM), tumor growth is usually strongly dependent on the bone marrow microenvironment [1]. Extramedullary disease (EMD) has been reported to occur in 6%–37%. The incidence can be as high as 70% in autopsy studies [2,3,4]. C-X-C-motif chemokine receptor 4 (CXCR4) expression and hypoxia have been reported to play a potential role in EMD growth [6,7]. High-risk cytogenetics are significantly enriched in MM with EMD [8,9,10,11,12], and studies consistently showed EMD to be associated with poor outcome [12,13,14,15,16]. There is no established approach for treatment of relapsed/refractory multiple myeloma (RRMM) with EMD
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