Real-World Retrospective Study of 46 Patients with Macrofocal Multiple Myeloma (MFMM)
Authors: Yan Wenqiang , Fan Huishou , Xu Jingyu , Liu Jiahui , Du Chenxing , Deng Shuhui , Sui Weiwei , Xu Yan , Qiu Lugui , An Gang 
Published: November 2021

Abstract
Real-world retrospective study of 46 patients with Macrofocal multiple myeloma (MFMM)
Introduction:
Multiple myeloma is a clonal plasma cell malignant neoplasm characterized by bone disease and marrow involvement. However, we found that some myeloma patients presented multiple lytic lesions, but didn't meet the diagnostic criteria of at least 10% clonal plasma cells in the bone marrow. And these patients were always diagnosed with myeloma by biopsy-proven plasmacytomas. This special myeloma entity has been called macrofocal multiple myeloma (MFMM) [1-2]. Considering that the data of this rare myeloma entity are limited, it is of great significance to investigate the clinical characteristics, genetic abnormality, treatment response and prognosis of MFMM patients.
Methods:
Based on the definition (BMPCs&lt;20% and multiple lytic lesions/plasmacytomas, without anemia, renal insufficiency or hypercalcemia) [3]，we identified 46 MFMM patients among 791 myeloma patients(5.8%) diagnosed at out hospital between January 2013 and December 2019. In the same period with same therapies, other 92 typical myeloma patients were selected as the control group.
Results:
Patient characteristics and comparisons between MFMM patients and the control group are depicted in Table 1. Of the 46 MFMM patients, 82.6% were &lt;65 years and 73.9% had at least 4 lytic lesions. And the incidence of plasmacytomas in MFMM patients was significantly higher than the control group (43.5% vs 18.5%, p&lt;0.05). According to the international staging (ISS) and the Revised ISS, advanced stage patients in the MFMM group was less common than controls (p&lt;0.05). Regarding to the cytogenetics, the high-risk features was infrequent in patients with MFMM compared to typical myeloma patients (15.8% vs 32.2%, p=0.058). And t (11;14) could be observed in 32.4% MFMM patients and 9.4% myeloma patients (p&lt;0.05).
The treatment patterns of the two groups were similar; about 30% of the patients received ASCT, and 80% patients received proteasome-inhibitors based regimen as the induction therapy. Concerning about the best response to treatment, the CR rate of the MFMM group was significantly higher than the controls (78.2% vs 60.8%, p&lt;0.05). As of June 2021, the median follow-up time was 37.9 months. The median progression-free survival in the study and control groups were 77.5 vs 39.8 months, respectively (p&lt;0.05). The overall survival (OS) of MFMM patients was significantly longer than typical myeloma patients during the same period with similar therapies (not reached vs 68.2m, p&lt;0.05).
Conclusion:
In conclusion, Macrofocal multiple myeloma is a special entity of MM, which is characterized with multiple lytic lesions, more extramedullary diseases, less bone marrow infiltration, and fewer adverse features. And the MFMM patient could achieve deep remission and prolonged OS in the era of novel agents.
References:
[1] Dimopoulos MA, Pouli A, Anagnostopoulos A, et al. Macrofocal multiple myeloma in young patients: a distinct entity with favorable prognosis. Leuk Lymphoma. 2006;47(8):1553-1556.
[2] Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15(12):e538-e548.
[3] Katodritou E, Kastritis E, Gatt M, et al. Real-world data on incidence, clinical characteristics and outcome of patients with macrofocal multiple myeloma (MFMM) in the era of novel therapies: A study of the Greco-Israeli collaborative myeloma working group. Am J Hematol. 2020;95(5):465-471.
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.