Characteristics and Outcomes of Patients With Relapsed/Refractory Multiple Myeloma After Exposure to Lenalidomide in First Line of Therapy: A Single Center Database Review in Greece.

BACKGROUND: The increasing use of lenalidomide (Len) in first-line (1L) therapy of multiple myeloma (MM) has led to a significant proportion of patients becoming Len-refractory following 1L treatment. However, there are limited real-world data on treatment strategies and outcomes of patients who become Len-refractory following 1L therapy. PATIENTS AND METHODS: This real-world retrospective cohort study analyzed Len-refractory and non-Len-refractory patients who received 1L Len and initiated second-line (2L) therapy at a Greek MM center. The Len-exposed cohort (n = 249) included 55.4% Len-refractory patients after 1L. RESULTS: Compared to non-Len-refractory patients, Len-refractory patients more frequently had high-risk cytogenetics and Revised-International Staging System-3 disease stage at diagnosis, and had shorter progression-free survival (PFS) following 1L therapy. Len-refractory versus non-Len-refractory patients more frequently received triplets (59% vs. 40%), anti-CD38 agents (20% vs. 9%) and pomalidomide (22% vs. 13%). The overall response rate was 53% for Len-refractory patients and 64% for non-Len-refractory patients in 2L therapy; median PFS was 10.7 vs. 18.3 months, respectively. Median overall survival (OS) was shorter for Len-refractory patients vs non-Len-refractory patients (23.8 vs. 53.6 months). Len refractoriness was an independent prognostic factor for both PFS and OS in Len-exposed patients. CONCLUSION: In this real-world Len-exposed cohort, Len-refractory patients receiving 1L Len experienced poorer survival outcomes than non-Len-refractory patients, highlighting the unmet need in this patient population which has driven the development of novel therapies.

Exploring super-Gaussianity toward robust information-theoretical time delay estimation.

Time delay estimation (TDE) is a fundamental component of speaker localization and tracking algorithms. Most of the existing systems are based on the generalized cross-correlation method assuming gaussianity of the source. It has been shown that the distribution of speech, captured with far-field microphones, is highly varying, depending on the noise and reverberation conditions. Thus the performance of TDE is expected to fluctuate depending on the underlying assumption for the speech distribution, being also subject to multi-path reflections and competitive background noise. This paper investigates the effect upon TDE when modeling the source signal with different speech-based distributions. An information theoretical TDE method indirectly encapsulating higher order statistics (HOS) formed the basis of this work. The underlying assumption of Gaussian distributed source has been replaced by that of generalized Gaussian distribution that allows evaluating the problem under a larger set of speech-shaped distributions, ranging from Gaussian to Laplacian and Gamma. Closed forms of the univariate and multivariate entropy expressions of the generalized Gaussian distribution are derived to evaluate the TDE. The results indicate that TDE based on the specific criterion is independent of the underlying assumption for the distribution of the source, for the same covariance matrix.

Toward bias minimization in acoustic feedback cancellation systems.

A novel technique for bias suppression within acoustic feedback cancellation systems is proposed. This is achieved based on the use of all-pass filters in the forward part of the hearing aid. The poles of these filters are made time-varying, which results in a frequency response with constant magnitude and varying phase. This is a desired feature of the proposed approach, since the results from human psychoacoustics show that the human ear is not sensitive to moderate phase perturbations. The derivation of the proposed algorithms for the time variation of the location of the poles of all pass filters is based on a rigorous analysis of the phenomenon of bias in acoustic systems. Practical issues, such as the dependence of the steady-state error on the order of the all-pass filter, the number of varying poles, and their standard deviation are examined and strategies for the variation of the poles are introduced. Results obtained from a simulated hearing aid are provided to support the analysis. The quality of the processed audio signals is evaluated through subjective tests.