A Marrowing Tale: A Case of Multiple Myeloma Refractory to Multiple Lines of Treatment

Multiple myeloma (MM) remains primarily a disease of the elderly, with a median age of 66 at presentation. Though the development of newer therapeutic agents and improvement in supportive care has significantly improved the outcomes of MM in younger patients over the last few decades, most studies suggest that improvements are only marginal at best in the elderly patient population. The availability of new combination regimens and autologous stem cell transplant has increased treatment options for elderly patients. However, even considering breakthrough treatment over the years, such factors as poor performance status, toxicities from prior combination therapies, and preexisting immune dysregulation may contribute to premature relapse and refractory multiple myeloma.

Our patient was an 80 y.o. Caucasian male with a past medical history of hypothyroidism, prostate cancer status post radiation, and multiple myeloma diagnosed in 2022 who last presented to Laredo Medical Center in April 2025 with a complaint of lower back pain. He had been requiring regular pRBC and platelet transfusions prior to hospitalization given worsening cytopenias. On admission, his platelets were 7,000 and hemoglobin was 7 for which he received transfusions. Chest X-ray on admission would reveal a pathologic compression fracture sustained at T9. Given that the patient had been on multiple lines of therapy for his multiple myeloma over the three years since his diagnosis and now recently with profound pancytopenia, oncology recommended an updated bone marrow biopsy to investigate any other possible etiologies. Due to the patient's pancytopenia and performance status, he was unfortunately not deemed a candidate for further therapy. Repeat biopsy would demonstrate plasma cell myeloma with 100% bone marrow involvement.

The patient had previously been on several lines of treatment for his multiple myeloma since his diagnosis in 2022. In 2022, he had started on initial treatment with CyBorD with denosumab. As per records, he would go on to try lenalidomide, pomalidomide, and ixazomib, though unfortunately over the years his myeloma markers overall worsened. At one point, selinexor was proposed, but his coverage unfortunately was not compatible with this medication. Of note, the patient was a Vietnam War veteran with confirmed exposure to Agent Orange, and he had also undergone recent radiation therapy for previously diagnosed prostate cancer in 2022. And given the patient's comorbidities, he was deemed not a candidate for autologous stem cell transplant. These factors, along with age and his inadequate response to multiple lines of therapy, could have definitely both increased the patient's risk for multiple myeloma and impacted his unfortunate and refractory clinical course respectively. Had the patient not had previous malignancy contributing to immune dysregulation and decreased performance status pertinent to his age and comorbidities, the said combination therapies and novel lines of treatment may have been more effective for him.