Understanding the Mechanisms of Clonal and Non-clonal Cytopenia Following CAR-T Therapy for Multiple Myeloma or CD19+ Lymphoproliferative Disorder (LPD)

PRIMARY OBJECTIVE:

I. Determine the preexisting and therapy-emergent germline and somatic variants associated with an increased risk of clonal and non-clonal cytopenia following CAR-T cell therapy on research basis.

SECONDARY OBJECTIVE:

I. Characterize the baseline transcriptomic signature associated with non-clonal and clonal cytopenia following CAR-T therapy on research basis.

OUTLINE:

Patients undergo bone marrow aspiration and hair, buccal, and saliva sample collection up to 14 days prior to lymphodepleting (LD) therapy. Patients undergo clinical follow-up (CFU) on day 90 post-CAR-T therapy. Patients with unexplained cytopenia also undergo bone marrow aspiration for sequencing analysis on day 90 and at development of myeloid neoplasm post-cytotoxic therapies (MN-pCT) during CFU. Patients also undergo bone marrow aspiration at determination of clonal evolution or myeloid neoplasm if not done during on day 90.

Patients with unexplained cytopenia at day 90 are followed up every 90 days for up to 2 years until resolution. Patients without unexplained cytopenia are followed clinically for up to 2 years.

Inclusion criteria

• Age ≥ 18 years
• Histologically or cytologically confirmed diagnosis of multiple myeloma (MM) as defined in International Myeloma Working Group (IMWG) criteria or a CD19+ lymphoproliferative disorder (LPD) as defined by 2016 World Health Organization (WHO) classification
• Provide written informed consent
• Willingness to provide mandatory bone marrow aspirate specimens for correlative research. All bone marrow aspirate samples are collected during a clinical procedure
• Willingness to provide mandatory hair follicle specimens for correlative research
• Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
• Willingness to provide saliva and buccal samples for research

Exclusion criteria

• Ineligible for CAR-T therapy
• Patients diagnosed with myeloid neoplasm before CAR-T therapy