Clinical relevance of hypogammaglobulinemia, clinical and biologic variables on the infection risk and outcome of patients with stage A chronic lymphocytic leukemia

The prognostic effect of hypogammaglobulinemia (HGG), clinical and biologic characteristics on the infection risk and outcome has been retrospectively analyzed in 899 patients with stage A chronic lymphocytic leukemia (CLL). Low levels of IgG were recorded in 19.9% of patients at presentation, low levels of IgM and/or IgA in 10.4% and an additional 20% of patients developed HGG during the course of the disease. Before the start of any treatment, 160 (12.9%) patients experienced at least one grade ≥3 infection requiring a systemic anti-infective treatment and/or hospitalization. While IgG levels at diagnosis were not associated with an increased risk of grade ≥3 infection or with an adverse outcome, a significantly increased rate of grade ≥3 infections was recorded in patients with unmutated IGHV (p=0.011) and unfavorable FISH aberrations (p=0.009). Late onset HGG, more frequently recorded in patients with Rai stage I-II (p=0.001) and unmutated IGHV (p=0.001), was also associated with a higher rate of severe infections (p=0.002). These data indicate that, stage A patients with clinical and biologic characteristics of a more aggressive disease develop more frequently late onset HGG, grade ≥3 infections and require a closer clinical monitoring

Predictors of Unsustained Minimal Residual Disease Negativity in Multiple Myeloma (MM) Patients

: The prognostic impact of achieving and in particular maintaining MRD negativity in multiple myeloma is now established, therefore identifying among MRD-negative patients the ones at higher risk of losing MRD negativity is of importance. We analyzed predictors of unsustained MRD-negativity in patients enrolled in the FORTE trial (NCT02203643). MRD was performed by multiparameter flow-cytometry (sensitivity of 10-5) at premaintenance and every 6 months thereafter. The cumulative incidence (CI) of MRD resurgence and/or progression was analyzed in MRD-negative patients. 306/474 (65%) MRD-negative patients were analyzed. After a median follow-up of 50.4 months from MRD-negativity, 185/306 (60%) patients were still MRD-negative and progression-free, 118 (39%) lost their MRD-negative status and 3 patients (1%) died without progression. Amp1q vs. normal (4-years CI 63% vs 34), ≥2 concomitant high-risk cytogenetic abnormalities vs. 0 (4-years CI 59% vs 33%), Circulating tumor cells at baseline (high vs. low 4-years CI 62% vs. 32%) and time-to-reach MRD negativity post-consolidation vs. pre-consolidation (4-years CI 46% vs 35%) were associated with a higher risk of unsustained MRD-negativity in a multivariate Fine-Grey model. During the first 2 years of maintenance, patients receiving carfilzomib-lenalidomide vs. lenalidomide alone had a lower risk of unsustained MRD-negativity (4-years CI 20% vs 33%). CT# NCT02203643