Humoral immune reconstitution following therapy with daratumumab, carfilzomib, lenalidomide, and dexamethasone (Dara-KRd), autologous hematopoietic cell transplantation, and measurable residual disease-response-adapted treatment cessation.

Quadruplet induction, autologous hematopoietic cell transplant (AHCT), and measurable residual disease (MRD) response-adapted consolidation yield an unprecedented depth of response in newly diagnosed multiple myeloma. Patients treated on MASTER (NCT03224507) ceased therapy and entered active surveillance (MRD-SURE) after achieving MRD negativity. This study characterizes quantitative changes in the immunoglobulin (Ig) gene repertoire by next-generation sequencing and serum gamma globulin levels. Quadruplet therapy leads to profound hypogammaglobulinemia and reduction in the Ig gene repertoire. Immune reconstitution (IR) is delayed in patients who received post-AHCT consolidation compared to those who do not. Eighteen months after treatment cessation, there was no statistically significant difference between the groups.

High or low? Assessing disease risk in multiple myeloma.

Based upon the development of highly effective therapies such as immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies that target plasma cell biology, a dramatic improvement in overall survival has been observed for most patients with multiple myeloma (MM) over the past 2 decades. Although it is now commonplace for many patients with myeloma to live in excess of 10 years after diagnosis, unfortunately a large subset of patients continues to experience an aggressive disease course marked by substantial morbidity and early mortality. Many clinical biomarkers and staging systems in use today can help with prognostication, but accurate risk assessment can be difficult due to the presence of many different biomarkers with variable prognostic value. Furthermore, with the implementation of novel therapies and unprecedented rates of deep and durable responses, it is becoming apparent that risk assessment is best envisioned as a dynamic process that requires ongoing reevaluation. As risk and response-adapted approaches are becoming more commonplace, it is essential that clinicians understand the biological and prognostic implications of clinical, genomic, and response-based biomarkers in order to promote management strategies that will help improve both survival and quality of life for patients across the risk spectrum.