# Measurable therapeutic antibody in serum as potential predictive factor of response to anti-CD38 therapy in non-IgG-k myeloma patients

## TL;DR

This study suggests that detecting therapeutic antibodies in blood tests may help predict how well patients with multiple myeloma respond to anti-CD38 treatments.

## Contribution

The study identifies measurable therapeutic antibody in serum as a potential predictive biomarker for anti-CD38 therapy response in non-IgG-kappa myeloma patients.

## Key findings

- Positive IgGk immunofixation was associated with higher response rates and longer progression-free survival in patients receiving anti-CD38 therapy.
- Clinical factors like high BMI, higher hemoglobin, lower CRP, and lower monoclonal protein levels correlated with detectable therapeutic antibody.
- The appearance of therapeutic antibody on immunofixation may reflect drug pharmacokinetics, immune response, and tumor biology.

## Abstract

Multiple myeloma (MM) is a hematologic malignancy characterized by abnormal plasma cell proliferation in the bone marrow. Recent advancements in anti-CD38 monoclonal antibody therapies, such as daratumumab and isatuximab, have significantly improved MM patient survival. However, the lack of predictive factors of response to these therapies remains a challenge. Notably, anti-CD38 antibodies can interfere with laboratory tests, complicating response assessment. We conducted a retrospective study to evaluate the association between the appearance of positive IgGk (therapeutic antibody) on immunofixation/immunosubtraction (IF) and clinical parameters in 87 non-IgGk MM patients treated with anti-CD38 therapy. Positive IgGk IF was observed in 42 patients after a median of three treatment courses. Patients with positive IgGk IF had higher rates of complete/very good partial responses (p = 0.03) and improved progression-free survival (median not reached vs. 21.83 months, p < 0.01). High BMI (p = 0.03), higher hemoglobin (p = 0.02), lower CRP (p = 0.04), and lower monoclonal protein levels (p = 0.03) were associated with positive IgGk IF. Our findings suggest that monitoring therapeutic antibody appearance on IF may predict and optimize anti-CD38 therapy in MM. Potential explanations include the impact of patient factors (e.g. BMI) on drug pharmacokinetics, the relationship between antibody levels and immune response, and the influence of tumor biology. Further research is needed to elucidate the underlying mechanisms and clinical utility of this biomarker. Nonetheless, our results highlight the importance of considering therapeutic antibody detection when interpreting laboratory tests and managing MM patients receiving anti-CD38 therapies.

The online version contains supplementary material available at 10.1186/s40164-024-00547-x.