Background: Multiple myeloma(MM) is a neoplasm characterized by clonal proliferation of plasma cells. Spinal Cord Compression (SCC), as an acute complication of multiple myeloma, can result in irreversible neurological dysfunction such as paraplegia, disability, and death if not promptly intervened. SCC caused by bone-related extramedullary disease (EMD-B) of multiple myeloma is responsive to both radiotherapy and chemotherapy regimens. Early diagnosis and active intervention can significantly improve patient outcomes. However, there remains controversy regarding the optimal treatment regimen, and there is a lack of comprehensive discussion on the clinical features and management of SCC in multiple myeloma patients.

Methods: A total of 168 MM patients with spinal bone disease, epidural extramedullary lesions, and vertebral compression fractures diagnosed in Affiliated Hospital of Hebei University from June 2017 to February 2024 were screened, among whom, 35 patients (21%) had SCC. The baseline clinical characteristics, treatment regimens, progression-free survival (PFS), overall survival (OS), as well as the rate of early improvement in compression symptoms (≤2 courses) among SCC patients undergoing different treatment modalities were subjected to statistical analysis. Univariate and multivariate analyses were performed to identify prognostic factors influencing MM patients with SCC.

Results：Thirty-five patients were included in the study, with a median age of 65 years (range 43-87). Fifty-one percent of patients had an ISS stage of III. 46% of the patients exhibited high-risk cytogenetic abnormalities, including t(14,16), t(4,14), 1q21+, and p53 deletion. 9% (3/35) of the patients developed SCC due to vertebral fractures, which were relieved by surgery. 91% (32/35) of the patients developed SCC due to EMD-B; one patient died due to treatment complications and could not be evaluated; two patients discontinued treatment; thirteen patients experienced early improvement of compression symptoms, resulting in an early improvement rate of 62%.

Among the 28 cases of NDMM patients with SCC, 53% achieved early improvement in compression symptoms, with 87% receiving novel drug regimens (including 5 cases of ID regimens and 8 cases of VRD/VCD regimens), while the remaining 13% received traditional chemotherapy combined with innovative medication (VT-DECP). In the case of RRMM patients with SCC, out of the total 7 cases, 57% experienced early relief from compression symptoms. All these patients were treated using traditional chemotherapy in combination with innovative medication such as DT-PACE, KPD combined with bendamustine, DICE combined with pomalidomide, and Dara combined with DA-EPOCH.

By the end of the follow-up period, 66% (23/35) of the patients had succumbed, demonstrating a median PFS of 14 (5-46) months and a median OS of 28 (9-78) months. Univariate analysis revealed that improvement in early symptoms (P=0.002), ISS staging (P=0.027), hypoproteinemia (P=0.021), and hypercalcemia (P=0.043) were prognostic factors influencing patient survival. Furthermore, univariate analysis indicated that high-risk cytogenetics (P=0.932) and coexisting soft tissue plasmacytoma outside the spine (P=0.656) did not have a statistically significant impact on survival in this cohort. The group showing early symptom improvement demonstrated that a briefer treatment course to alleviate symptoms(1 course)(P=0.043) was a high-risk factor affecting survival. Multivariate analysis conducted concurrently early improvement (P=0.031, HR=3.582,95% CI:1.126-11.390)and hypoproteinemia(P = 0.043, HR =5.006, 95% CI:1.051 -23 .856) as independent prognostic factors.

Conclusions: This study demonstrates that the majority of SCC in MM is attributed to EMD-B, which has a worse prognosis than the overall MM population, similar to the prognosis reported in literature for soft tissue-related extramedullary disease (EMD-S). NDMM may benefit more from novel drug therapy, while RRMM may gain an advantage from combination therapy involving new drugs and chemotherapy. Early improvement in compression symptoms has an independent impact on survival, and EMD-B-related SCC may be an independent unfavorable prognostic factor independent of cytogenetics and extraosseous soft tissue plasmacytoma; however, further studies with a larger sample size are warranted.

Disclosures

No relevant conflicts of interest to declare.

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2024
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