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

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.

Acute GVHD classification based on the dynamics of GVHD skin involvement from its appearance to the start of systemic treatment.

We conducted a prospective study aimed at investigating the prognostic value of the dynamic of a-GVHD progression from cutaneous to visceral involvement. In 108 consecutive patients who underwent allogeneic HSCT, we classified a-GVHD according to a "GHVD skin dynamic": 18/82 patients started Corticosteroid (CS) within 48 h (Group 1); 13/82 started CS within days 3-7 (Group 2); Group 3A (n 31) was defined when Skin GVHD Overall Grade 1, left untreated for 1 week, showed an increase in involved body surface area <5 %; Group 3B (n 20), was defined when Skin GVHD Overall Grade 1, left untreated at 1 week, had an increase in involved body surface area >5%. These four groups had distinctive 2-y OS. Patients could be then grouped into "poor risk" (Group 1 and Group 3B) and "good risk" (Group 2 and Group 3A). "Poor risk" had inferior OS in univariate and multivariate analysis, (HR 2.222; 95% CL: 1.017-4.855; p 0.04). Among the patients with skin-only Grade 1 GVHD, subgroup 3A had an OS of 75.1% versus 39.8% found in subgroup 3B (p = 0.03). The dynamic of skin GVHD may be used to classify a-GVHD and guide treatment in Overall Grade 1 skin-only GVHD.

Clinical outcome of SARS-CoV-2 infections occurring in multiple myeloma patients after vaccination and prophylaxis with tixagevimab/cilgavimab.

Introduction: Patients with multiple myeloma (MM) frequently reported immune impairment with an increased risk for infection-related mortality. We aimed to evaluate the immune response in MM patients vaccinated for SARS-CoV-2 during active treatment. Methods: We enrolled 158 patients affected by active MM or smoldering MM (SMM) and 40 healthy subjects. All subjects received 2 or 3 doses of the BNT162b2 (Pfizer/BioNTech) vaccine, and the anti-spike IgG values were evaluated after every dose. We applied the Propensity Score Matching (PSM) as a consequence of the limited sample size and its heterogeneity to adjust for differences in baseline clinical variables between MM patients who achieved or not a vaccine response after 2 or 3 doses. Results: At 30 days from the second dose, the median antibodies level in MM was 25.2 AU/mL, lower than in SMM and in the control group. The same results were confirmed after the third dose, with lower median anti-spike IgG levels in MM, compared to SMM and control group. Following PSM, lack of response to SARS-CoV-2 complete vaccination plus boost was associated with age more than 70 years old and use of high-dose of steroids. We failed to identify an association between specific treatment types and reduced vaccine response. The use of prophylaxis with tixagevimab/cilgavimab for 40 non-responder patients after 3 doses of vaccine has proven to be an effective and safe approach in reducing the risk of serious illness in the event of a breakthrough SARS-CoV-2 infection, faced with a mild symptomatic course, and in providing protection instead of long-term humoral immune vaccine responses. Following PSM, only the high-risk cytogenetic abnormalities were associated with an increased risk of developing a breakthrough SARS-CoV-2 infection. Conclusion: Monitoring the immune response is fundamental in MM patients that remain highly vulnerable to SARS-CoV-2 despite the vaccine. The use of prophylaxis with tixagevimab/cilgavimab can guarantee better protection from the severe form of the disease.