Functional Recovery Following Intensive Upfront Therapy in Multiple Myeloma Patients With Poor Performance Status: A Case Series.

Patients with newly diagnosed multiple myeloma (MM) may present with profound functional impairment due to high disease burden, and an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 4 is often viewed as a barrier to intensive therapy despite potential reversibility. We report six newly diagnosed, bedbound MM patients (ECOG 4) treated with individualized multi-agent regimens incorporating proteasome inhibitors, immunomodulatory agents, and anti-CD38 monoclonal antibodies when feasible. Advanced features included extensive skeletal disease, renal dysfunction, hyperviscosity, and high-risk cytogenetics. All patients demonstrated rapid biochemical response, with a median M-protein reduction of approximately 75%; five of six achieved a very good partial response or better, including one complete response. Functional recovery paralleled depth of response, with a median time to meaningful improvement of 10 weeks. All patients improved to ECOG 2 or better, regaining ambulation and independence in activities of daily living. One patient proceeded to autologous stem cell transplantation and another completed stem cell mobilization. No irreversible treatment-limiting toxicities were observed. These findings suggest that severe functional impairment at presentation often reflects reversible disease burden and that aggressive, individualized therapy can result in substantial clinical and functional recovery in patients initially considered too debilitated for intensive treatment.