Survivorship in Patients with Multiple Myeloma Treated with Chimeric Antigen Receptor T-cell Therapy

PROJECT SUMMARY/ABSTRACT Multiple myeloma is the second most common hematologic cancer in the US and remains incurable, with virtually all patients developing relapsed or refractory disease after initial therapy. Chimeric antigen receptor T-cell therapy (CAR T) is a revolutionary new treatment for patients with relapsed/refractory multiple myeloma (RRMM) who have progressed on several prior treatments and have limited treatment options remaining. In clinical trials, RRMM patients treated with CAR T showed unprecedented treatment response rates and improved patient- reported outcomes (PROs), such as health-related quality of life (HRQOL) and symptom burden. CAR T is now available to RRMM patients as standard of care, offering patients new hope for durable remission and better HRQOL. However, clinical trials had stringent eligibility criteria and lacked racial and ethnic diversity, which limits the generalizability of findings to RRMM patients treated in standard of care. To address this limitation, we will establish a first-in-kind prospective cohort of real-world RRMM CAR T recipients at Moffitt Cancer Center, one of the leading high-volume US institutions offering standard of care CAR T for diverse RRMM patients. Within an evidence-based psychoneuroimmunology framework, we will evaluate psychosocial factors (i.e., depression, anxiety, social support) and immune-related factors (i.e., systemic inflammation, bone marrow immune microenvironment) as they relate to key clinical and patient-reported survivorship outcomes (i.e., incidence and severity of CAR T toxicities, treatment response, progression-free survival, HRQOL, and symptom burden). Immune-related factors may be especially relevant to this population’s survivorship, as CAR T harnesses a patient’s own immune system to kill cancer cells, and recipients can experience potentially life-threatening immune-mediated toxicities. Participants will complete PRO assessments and provide blood specimen samples for quantification of immune biomarkers at clinically defined timepoints, from pre-CAR T infusion (i.e., baseline) through one year. We will also use multiplex immunofluorescence staining and novel statistical methods developed by our team to characterize the abundance and spatial relationships of immune cells in the bone marrow microenvironment. This resource of highly phenotyped RRMM patients with systematically collected PRO data and biospecimens will allow us to identify psychosocial factors (Aim 1) and immune-related factors (Aim 2) associated with key clinical and patient-reported survivorship outcomes among real-world patients treated with CAR T as part of standard of care. Study findings will have direct clinical implications. Identifying psychosocial and immune-related factors associated with CAR T survivorship outcomes will inform the development of patient education and clinical decision-making tools. Findings will also elucidate modifiable targets for developing and implementing supportive care interventions and use of inflammation-reducing medications. Long-term, this research will improve survivorship for RRMM patients treated with CAR T, a growing yet understudied population living with incurable cancer.