Survival benefit of ixazomib, lenalidomide and dexamethasone (IRD) over lenalidomide and dexamethasone (Rd) in relapsed and refractory multiple myeloma patients in routine clinical practice.

BACKGROUND: We have performed a head to head comparison of all-oral triplet combination of ixazomib, lenalidomide and dexamethasone (IRD) versus lenalidomide and dexamethasone (RD) in patients with relapsed and refractory multiple myeloma (RRMM) in the routine clinical practice. METHODS: A total of 344 patients treated with IRD (N = 127) or RD (N = 217) were selected for analysis from the Czech Registry of Monoclonal Gammopathies (RMG). Descriptive statistics were used to assess patient's characteristics associated with the respective therapy. The primary endpoint was progression free survival (PFS), secondary end points included response rates and overall survival (OS). Survival endpoints were plotted using Kaplan-Meier methodology at 95% Greenwood confidence interval. Univariable and multivariable Cox proportional hazards models were used to evaluate the effect of treatment regimens and the significance of uneven variables. Statistical tests were performed at significance level 0.05. RESULTS: In the whole cohort, median PFS for IRD was 17.5 and for RD was 11.5 months favoring the all-oral triplet, p = 0.005; in patients within relapse 1-3, the median PFS was 23.1 vs 11.6 months, p = 0.001. The hazard ratio for PFS was 0.67 (95% confidence interval [CI] 0.51-0.89, p = 0.006). The PFS advantage translated into improved OS for patients treated with IRD, median 36.6 months vs 26.0 months (p = 0.008). The overall response rate (ORR) was 73.0% in the IRD group vs 66.2% in the RD group with a complete response rate (CR) of 11.1% vs 8.8%, and very good partial response (VGPR) 22.2% vs 13.9%, IRD vs RD respectively. The IRD regimen was most beneficial in patients ≤75 years with ISS I, II, and in the first and second relapse. Patients with the presence of extramedullary disease did not benefit from IRD treatment (median PFS 6.5 months). Both regimens were well tolerated, and the incidence of total as well as grade 3/4 toxicities was comparable. CONCLUSIONS: Our analysis confirms the results of the TOURMALINE-MM1 study and shows benefit of all-oral triplet IRD treatment versus RD doublet. It demonstrates that the addition of ixazomib to RD improves key survival endpoints in patients with RRMM in a routine clinical setting.

Multicentered patient-based evidence of the role of free light chain ratio normalization in multiple myeloma disease relapse.

INTRODUCTION: The normalization of free light chain ratio (FLCr) has been introduced as a marker of stringent complete remission (CR) of multiple myeloma (MM). There is currently a lack of literature assessing the role of FLCr on MM disease progression and remission status. PATIENTS AND METHODS: A multicentered retrospective review of 125 patients with MM in CR and various FLCr values was completed. Parameters of interest included patient demographics, FLCr values, complete remission (CR)/relapse status, and time to progression (TTP). The FLCr values were recorded to provide time-dependent findings on the role of FLCr on progression-free survival and overall survival (OS). RESULTS: The mean follow-up time of 125 patients from five hospitals in the Czech Republic was 31 months. A total of 47.2% of patients relapsed (54 of 125) during the follow-up period. The median TTP of patients with normal FLCr (n = 66) was 54.4 and 40.2 months for patients with abnormal FLCr (n = 59) (P = 0.217). None of the patients reached median overall survival regardless of FLCr values (P = 0.821). In the subgroup of newly diagnosed patients after upfront autologous stem cell transplantation (ASCT), there were 55.6% of patients (35 of 63) with normal FLCr and 44.4% (28 of 64) with abnormal FLCr. A total of 34.9% of patients (22 of 63) relapsed in this subgroup. Within the abnormal FLCr patients, a median TTP was 56.3 months, but no median TTP was reached among the normal FLCr patients (P = 0.746). Median OS in patients with normal (nFLCr) and abnormal FLCr (aFLCr) was not reached (P = 0.787). CONCLUSION: We did not observe any benefit from FLCr normalization in CR in myeloma patients in terms of progression-free survival or overall survival.

Alveolar antral artery: cone beam computed tomography study and clinical context.

Purpose: Anastomosis between posterior superior alveolar artery and infraorbital artery can go through bony canal in the lateral wall of the maxilla. This artery is called alveolar antral artery. It can complicate lateral sinus lift procedure by bleeding and hemosinus formation or bone graft wash out. The artery can also go in soft tissues where is not visible on cone beam computed tomography. In previous studies, the relation of this artery to sinus floor or alveolar process was measured. These structures are highly unstable during lifetime and after tooth loss. The aim of this study is to study presence and relations of bony canal in the lateral maxillary wall, to characterize the group of patients which is more likely to have bone canal in the lateral maxilla. The aim and the novelty of this study is the describing of the relationship of the bony canal to the more stable structure of hard palate and describing the relation of presence of bony canal on width of maxillary sinus, and to facilitate the prediction of presence of the alveolar antral artery. Materials: The cone beam computed tomography scans of the patients (251 in number) of the university hospital were examined for presence of alveolar antral artery (148 was fulfilled inclusion criteria), patient were characterized by gender, age, and sinus type (wide, average, narrow). The diameter of the bony canal and its relation to the level of sinus floor and hard palate were measured. Results: The cone beam computed tomography scans of 148 patients, out of it 55 man (37,2%) and 93 women (62,8%). Bony canal containing alveolar anastomosis was found in 69 cases (57,0%). Presence of the bony canal in the lateral wall of maxillae showed statistical probability depending on age with p = 0, 064 according to Mann-Whitney test. The older patients have more likely the bony canal. The presence of the alveolar antral artery was found more likely in the wide sinuses. The hard palate level can serve as a prediction point of alveolar antral artery only in first molar and second premolar region. In accordance with previous studies the width of bony canal is significantly higher in group of man (p = 0, 015). There was found a correlation between smaller distance of bony canal from sinus floor in the presence of teeth (p = 0, 067). After tooth loss the distance between sinus floor and bony canal increases, but the distance of bony canal to hard palate level stays constant. This can be explained hypothetically so that periodontal ligaments and root surface acts as a barrier for sinus pneumatization. Conclusion: Lateral sinus lifting in some cases can be unenviable, the knowledge about alveolar antral artery anatomy can reduce the risk of arterial bleeding. The cone-beam computed tomography is a routine examination prior to augmentation surgery and therefore the data obtained from it has an impact on clinical practice.