Extramedullary Disease in MM Tough to Treat, Even With Newer Therapies, Study Says

A recent study examined the outcomes of patients with relapsed/refractory multiple myeloma (RRMM) and extramedullary disease (EMD) to see if carfilzomib had any effect, as research in this area is limited.

Outcomes were worse for these patients, and the authors said their findings indicate that evaluation of extramedullary response using imaging is needed in this group.

EMD—in which the multiple myeloma (MM) cells form tumors outside of the bone marrow—has been reported to occur in 6% to 37% of patients; the authors reported that some autopsy studies have found an incidence as high as 70%. There is no standard treatment for RRMM with EMD; the various strategies that do exist do not lead to long-term disease-free survival.

In this study, the authors retrospectively analyzed 45 patients with extramedullary RRMM treated with carfilzomib, a second-generation proteasome inhibitor, from June 2013 to September 2019. EMD included paraosseous lesions originating from bone and extramedullary plasmocytomas without direct bone contact. The diagnosis of EMD was based on the analysis of tumor bulk or through the use of imaging, including computed tomography (CT), diffusion weighted magnetic resonance imaging (MRI), or positron emission tomography (PET).

Carfilzomib was given on days 1, 2, 8, 9, 15, and 16 as an intravenous short infusion in a 28-day cycle. The dose started at 20 mg/m² on days 1 and 2 of the first cycle, increasing to 27 mg/m² on day 8 if tolerated (doses were escalated or reduced according to the physician). Carfilzomib was administered in combination with at least 1 additional drug, including dexamethasone, immunomodulatory drugs (lenalidomide and pomalidomide), an alkylating agent, and a biologic (daratumumab and elotuzumab).

The median age at the start of carfilzomib was 64 years; the majority of the patients were male. Twenty (44%) and 25 (56%) patients had paraosseous manifestation and EMD without adjacency to bone, respectively.

The serological overall response rate (ORR) was 59%, and extramedullary response was evaluable in 33 patients; 9 (27%) of them achieved partial remission (ORR, 27%).

But in the majority of patients, 15, or 33%, had no extramedullary response despite serological response; 6 of these patients achieved an extramedullary mixed response. Intratumor genomic heterogeneity with advanced clones located to EMD might explain the lower response rates compared with intramedullary disease, the authors wrote.

The median progression-free survival (PFS) and overall survival (OS) were 5 (95% CI, 3.5-6.5) and 10 (95% CI, 7.5-12.5) months, respectively.

Moreover, EMD without adjacency to bone was associated with a significantly inferior PFS (P = .004) and OS (P = .04) compared with paraosseous lesions.

"EMD still heralds poor prognosis, especially in patients being refractory to the last therapy line," said the researchers, calling treatment an urgent unmet medical need.

Reference

Zhou X, Flüchter P, Nickel K, et al. Carfilzomib based treatment strategies in the management of relapsed/refractory multiple myeloma with extramedullary disease [published online April 23, 2020]. Cancers (Basel). doi: 10.3390/cancers12041035.