Clinical Outcomes of Extramedullary Multiple Myeloma in the Era of Novel Agents

Introduction: Extramedullary multiple myeloma (EMM) is defined as presence of plasma cell infiltration outside of the bone marrow. EMM is predictive of adverse prognosis and should be treated as high-risk multiple myeloma (MM). Optimal treatment strategy is not well defined due to lack of prospective therapeutic studies in this patient population.

Methods: We performed a single-center, retrospective chart review of patients with EMM with soft tissue involvement at the time of initial diagnosis with MM.

Results: Patients with soft tissue EMM diagnosed between 2015-2016 were identified (n=10). The median age of patients was 62.4 years. Seventy percent of patients were males. Eighty percent of patients had standard risk, and 20% had high-risk chromosomal abnormalities by FISH, defined as the presence of 17p deletion, t(4;14), t(14;16), or t(14;20). Of note, 80% of the patients (8/10) were found to have chromosome 1 abnormalities. Gain of 1q was seen in 50% of patients; the rest were found to harbor gain of 1p, t(1:1), and t(1q21). Based on ISS staging, 10% of patients had stage I, 40% stage II, and 50% stage III disease. Paraspinal, mediastinal and retroperitoneal soft tissue involvement were the most common sites of EMM, followed by liver, cutaneous and pulmonary sites. Half of the patients had more than 3 sites of EMM. Median time of follow-up was 12.5 months.

All patients had received initial induction therapy with triplet combination regimen: 50% were treated with bortezomib/lenalidomide/dexamethasone (VRD), and 50% with cyclophosphamide/bortezomib/dexamethasone (CyBorD). Patients had received a median 4 lines of therapy. Among the patients reviewed, none achieved CR, 60% achieved VGPR and 40% achieved only PR as best response to therapy after the course of induction. Thus, overall response rate with front line triplet induction was 100%, but the responses were extremely short-lived. With the median follow-up of 12.5 months, 80% of patients developed rapid progression of disease (PD), with median PFS of 6 months. At a median follow-up of 12.5 months OS was only 50% (5/10).

Five patients received daratumumab-based combination during the course of progression of disease (PD). Median PFS while on daratumumab-containing regimen was 3 months. All patients were deemed potentially transplant-eligible at diagnosis and 40% of them were transplanted. However 60% of patients were unable to move forward with autologous SCT due to rapid and aggressive PD.

Conclusions: Our results indicate that the presence of soft tissue EMM at the time of diagnosis portends an exceedingly poor prognosis, short duration of PFS and a very limited OS even in the era of novel therapies. Despite the advent of monoclonal antibodies, the prognosis remains grim in this sub-group. There may be an association between chromosome 1 abnormalities and soft tissue EMM. Further research efforts are required to define optimal therapeutic regimen for this subset of myeloma patients.