Analysis of clinical characteristics, treatment response, and prognosis among 67 patients with anaplastic multiple myeloma

Abstract

Background: Anaplastic multiple myeloma (AMM) is a type of distinctive MM with a poor prognosis. AMM is mostly reported as individual cases, an accurate incidence and strict clinical definition are lacking.

Methods: Sixty-seven patients with AMM were identified and then analyzed in the clinical database of patients with MM from January 2017 to September 2024.

Results: The incidence of AMM among patients with MM was 3.3%. The IgD type accounted for 11.9% of patients, with 40.3% and 53.7% kappa and lambda light chains, respectively. Plasmablasts with larger diameters and multinuclear variations accounted for 46.7% from bone marrow or extramedullary disease (EMD) based on pathologic morphology; the average Ki-67 was 64.8%. The incidence of EMD was 49.3%. Lactic dehydrogenase (LDH) was elevated in 44.8% of patients and 49.3% of patients were International Staging System (ISS) III. The frequencies of 1q21, t (4; 14), and t (14; 16) in high-risk genes were 60.5%, 39.5%, and 18.4%, respectively. Double and triple gene hits were detected in 36.8% and 13.2% of patients, respectively. Fifty-six patients received treatment with bortezomib-based regimens. The progression-free survival (PFS) and overall survival (OS) of AMM patients in the autologous stem cell transplantation (ASCT) group were prolonged compared to patients who did not undergo ASCT with a median PFS and OS of 5.0 versus 25.0 and 17.0 versus 36.0 months, respectively (P = 0.0246 and P = 0.0119, respectively). At the time of the last follow-up, 71.4% of patients had died with 77.5% experiencing disease progression. A high neutrophil-to-lymphocyte ratio (NLR) and no ASCT were also independent prognostic factors for AMM patients.

Conclusions: The incidence of AMM is rare. The characteristics of these AMM patients included extensive proliferation of plasmablasts and widespread EMD formation, AMM patients also exhibit more invasive clinical manifestations and a short survival. Patients who underwent sequential ASCT after receiving bortezomib-based regimens partially overcame the poor prognosis of AMM.

Keywords: Anaplastic multiple myeloma; Clinical characteristics; Prognosis; Treatment response.

Fig. 1

Characteristics of medical examinations in AMM patients. a. EMDs during diagnosis presented in whole body PET-CT; b. Bone marrow smears showed atypical plasma cells: giant multilobed, nuclei divided, nucleoli prominent (May-Grünwald-G iemsa stain, × 1000); c. Flow cytometry of bone marrow showed a red phenotype of clonal plasma cells; d. The sharp black M peak presented on Serum protein electrophoresis

Fig. 2

Images of immunohistochemical staining in bone marrow biopsies of AMM patients. The immunohistochemical staining of pathological morphology from bone marrow biopsy showed that tumor cells had many anaplastic (large multinucleated) forms (a). Tumor cells were positive for CD38 (b), CD138 (c), and cytoplasmic lambda light chain (d), but negative for cytoplasmic kappa light chain (e). Tumor cells were positive for Ki67 (f), CD56 (g), but negative for CD19(h), and EBER (i)

Fig. 3

Impact of different ages on survival. At the time of diagnosis, the median PFS and OS of AMM patients aged < 60 years and ≥ 60 years were 14.5 vs 4.0 months and 32.5 vs 14.5 months, respectively. There was no significant difference in PFS between the two groups (P > 0.05), but the difference in OS was statistically significant (P = 0.0026)

Fig. 4

Impact of EMD on survival. Survival analysis was conducted on groups with 0, 1, 2–4, and ≥ 5 merged EMD sites, and the median PFS for EMD 2–4 and ≥ 5 sites were 14.0 vs. 1.0 months, respectively, with statistically significant differences (P = 0.0348), as shown in (a) and (b). Further analysed EMD into intra groups: group without EMD (EMD = 0), with only bone- related EMD (EMD-b), with only soft tissue- related EMD(EMD-s), and patients with both EMD-b and EMD-s (both EMD). From without EMD to both EMD group, there was a trend of shortened PFS and OS. The OS of patients with both EMD and those without EMD were 11.0 vs. 31.0 months, with a statistically significant difference (P = 0.0302). There was no statistically significant difference between the remaining groups, as shown in (c) and (d)

Fig. 5

Impact of ASCT on survival. The PFS and OS of AMM patients in the ASCT group were prolonged compared to patients who only receive bortezomib- based regimens (who failure to undergo ASCT, no ASCT) with a median PFS and OS of 5.0 and 25.0 and 17.0 and 36.0 months, respectively (P = 0.0246 and P = 0.0119, respectively, as shown in (a) and (b)

Fig. 6

Impact of NLR on survival. By plotting the ROC curve(a), the cutoff value of NLR was calculated to be 2.855. The median PFS and OS below and above this cutoff value were 26.5 vs. 5.0 months and 34.5 vs. 21.0 months, respectively, with statistically significant differences (both P < 0.001). As shown in (b) and (c), respectively