Walking on myeloma

Bart Barlogie and Joshua Richter

A 60-year-old man who had had immunoglobulin G κ multiple myeloma since 2008 underwent 2 melphalan 200 mg/m2–based autologous transplantations. Initial genomic analysis revealed translocation (4;14). He had received 12 lines of therapy, including all US Food and Drug Administration–approved therapies and checkpoint inhibitors, with numerous relapses. The most recent genomic evaluation confirmed IGH-FGFR3 and IGH-MMSET fusions, loss of BIRC3 and CDKN2C, and a splice site within NFKB1A. Although he has never had osteolytic bone disease, a biopsy shows confluent sheets of atypical plasma cells infiltrating skeletal muscle (panels A and B; hematoxylin and eosin stain, original magnification ×100 [A] and ×400 [B]), and immunohistochemical labeling for ki67/mib1 shows a proliferation index of 60% to 70% (panel C; original magnification ×400). With positron emission tomography/computed tomography–confirmed focally progressive disease in the calves and plantar aspects of his feet bilaterally, he is “walking on myeloma” (arrows indicate active myeloma).

Oligosecretory status and absence of bone marrow involvement with minimal residual disease negativity require frequent imaging studies, making him ineligible for clinical trials. He maintains otherwise excellent clinical performance status and is responding to 28-day metronomically scheduled therapy: doxorubicin and cisplatin both at 1.0 mg/m2 per day by continuous infusion; flat-dose vincristine 0.07 mg per day plus bortezomib 1.0 mg/m2 on days 1, 4, 7, 10, 13, 16, 19, 22, 25, and 28; dexamethasone 12 mg on days 1 to 4, 7 to 10, 13 to 16, 19 to 22, and 25 to 28; daratumumab 16 mg/kg weekly for 4 weeks; and proteasome inhibitor–synergizing nelfinavir 1250 mg twice daily, complemented by radiation therapy to both legs.


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