Light-chain amyloidosis with concomitant symptomatic myeloma (CRAB-SLiM features): clinical characteristics, cytogenetic abnormalities, and outcomes

Abstract

Background

Patients with light-chain (AL) amyloidosis and concomitant multiple myeloma (MM) are known to have a worse prognosis, while the prognostic implication of cytogenetic abnormalities (CA) and optimal treatment schemes are not well-established. By comparing patients with MM or AL amyloidosis (AL) alone, this study aimed to evaluate the clinical characteristics, CA, and outcomes of patients with AL amyloidosis and concomitant symptomatic MM (MM-AL) and sought to provide evidence for their management.

Methods

In total, 915 consecutive patients with newly diagnosed AL amyloidosis or MM were retrospectively analyzed. Patients were classified as MM-alone, MM-AL or AL-alone. The presence of symptomatic MM was based on the International Myeloma Working Group criteria, and the diagnosis of AL amyloidosis was confirmed by Congo-red-positive biopsy and immunoelectron microscopy.

Results

Of 915 patients, 658, 106, and 151 were in the MM-alone group, MM-AL group, and AL-alone group, respectively. The three groups shared a similar incidence rate of CA, while the prevalence of t(11;14) was significantly higher in the AL-alone group than in the MM-AL and MM-alone group (40.7% vs. 25.7% vs. 16.6%, p < 0.001), and the prevalence of del13q, gain1q21 and high-risk CA (HRCA) decrease in turn in MM-alone, MM-AL and AL-alone group (del13q, 46.5% vs. 39.4% vs. 28.5%, p < 0.001; gain1q21, 52.6% vs. 45.2% vs. 27.3%, p < 0.001; HRCA, 27.5% vs. 16.0 vs. 7.3%, p < 0.001). The progression-free survival (PFS) and overall survival (OS) of MM-AL patients (median, 12.8, and 25.2 months) were significantly inferior to patients with MM-alone and AL-alone. No significant difference in PFS and OS was found between MM-AL patients with and without HRCA. When stratified by the type of plasma cell disease and status of t(11;14), patients with MM-AL and t(11;14) presented the worst OS (median, 8.2 months, p < 0.001). Regarding the management of MM-AL, extended cycles of induction therapy and the use of maintenance therapy contributed to a better prognosis.

Conclusions

There was an apparent discrepancy in the distribution and prognostic implication of CA among different plasma cell diseases. Patients with MM-AL had the worst clinical outcomes, requiring extended duration of induction therapy and maintenance therapy.