Incidence and clinical features of extramedullary multiple myeloma in patients who underwent stem cell transplantation

Abstract

Summary Extramedullary disease (EMD), defined as an infiltrate of clonal plasma cells at an anatomic site distant from the bone marrow, is an uncommon manifestation of multiple myeloma. Six hundred and sixty-three consecutive patients with multiple myeloma who underwent stem cell transplantation between January 2005 and December 2011 were assessed for the presence of EMD. A cohort of 55 patients with biopsy-proven EMD was identified, comprising 8.3% of the total study population. EMD was present at the time of diagnosis in 14.5% of cases and at the time of relapse in 76% of patients. The most common EMD presentations at relapse were liver involvement and pleural effusions. EMD specimens had high expression of CD44 (92%) and moderate expression of CXCR4. The median overall survival from time of myeloma diagnosis was 4.1 years (95% confidence interval: 3.1, 5.1) and the median overall survival from time of EMD diagnosis was 1.3 years (95% confidence interval: 0.8, 2.3). This report demonstrates that the incidence of EMD has not increased with the introduction of novel agents and stem cell transplantation. The most common EMD presentations in the relapsed setting were liver and pleural fluid. The presence of CD44 and CXCR4 expression may represent new markers of EMD that warrant further investigation.

How I treat extramedullary myeloma

“…At the time of myeloma diagnosis, EMM is found in 6% to 8% of patients using a baseline staging that includes whole-body MRI and/or PET-CT. [13][14][15][16] During the disease course, the prevalence of EMM increases, and EMM is found in 10% to 30% of patients.…”

Aggressive and extramedullary plasma cell myeloma evade bone marrow flow cytometric minimal residual disease detection

“…Although the patient numbers are low and follow-up short, it is tempting to draw comparisons with two recent larger studies involving newly diagnosed and multiply treated patients (Paiva et al, 2011;Weinstock et al, 2015). The first, a study of 260 elderly patients with newly diagnosed myeloma treated with novel agents, showed that in 7/31 patients that achieved iCR but with persistent paraprotein by immunofixation, the M-Protein ultimately disappeared within 9 months (Paiva et al, 2011).…”

“…The first, a study of 260 elderly patients with newly diagnosed myeloma treated with novel agents, showed that in 7/31 patients that achieved iCR but with persistent paraprotein by immunofixation, the M-Protein ultimately disappeared within 9 months (Paiva et al, 2011). In the second study of 663 consecutive patients who underwent stem cell transplantation for PCM, 55 (8Á3%) cases had EMD, comprising 8 (14Á5%) for whom EMD was present at diagnosis and 42 (76%) patients who developed EMD at the time of relapse (Weinstock et al, 2015). The inherent fallibility of BM-based MRD assessment of PCM in the setting of patchy disease was exemplified by two separate groups, expert in FC, who demonstrated occult marrow disease by FC in 49% and 68% of patients with solitary plasmacytoma of bone respectively (Hill et al, 2014;Paiva et al, 2014), and 38% of patients with EMD , thus confirming the absence of detectable BM disease in the substantial remainder.…”

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We were interested to read the recent publication by Weinstock and colleagues (Weinstock et al, 2015), which described the incidence and clinical features of 55 cases of biopsy-proven extramedullary multiple myeloma, derived from a large cohort of consecutive patients who underwent stem cell transplantation, noting that the majority of this uncommon manifestation occurred at relapse. These findings were of particular interest to us as we recently collected data from patients undergoing minimal residual disease (MRD) assessment for plasma cell myeloma (PCM) by flow cytometry (FC), and focused our attention on those for whom disease was undetectable in the bone marrow (BM) but present elsewhere, and also found, with smaller numbers, that extramedullary disease (EMD) was more often the reason for a 'false 20* S, HDT, I (patient 6) 3 I, P, HDT (patient 4) 3 S, I, HDAC (patient 5) 1 P 1 S, HDT x 2, I 2 S, HDT 2 S, HDT, P 1 S, HDT, I, P (patient 8) 1 S, HDT x 2, I, P (patient 7) 3 S, HDT, I, P, HDAC 3 S, HDT x 2, I, P, HDAC 1 S, HDT, I, P, Ex, Ex 1 *Uniformly treated (N = 16); ISS, International Staging System; S, standard therapy (corticosteroid and conventional cytotoxic chemotherapy); I, immunomodulatory (thalidomide or lenalidomide); HDT, high dose therapy (melphalan/autologous stem cell transplant with cyclophosphamide stem cell mobilization); HDAC, histone deacetylase inhibitor; P, proteasome inhibitor; Ex, experimental agent.

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Successful treatment with lenalidomide dexamethasone for second relapse of a patient with non-secretory multiple myeloma with extramedullary liver plasmacytomas: A case report

“…Extramedullary disease is spreading hematogenously and refers to soft tissue infiltration by plasma cells (liver, CNS, skin, pancreas, lymph nodes, kidneys, pleural effusions) [6,7]. EMM is diagnosed at approximately 6-8% of the MM patients at the initial diagnosis while the prevalence increases in the relapsed/ refractory setting and reaches almost 10-30% of the patients [8][9][10][11]. Extramedullary plasmacytomas usually show a more aggressive, plasmablastic morphology [6].…”