Pomalidomide Treatment in Relapsed/Refractory Multiple Myeloma Patients-Real-World Data From Hungary.

Pomalidomide is a third generation immunomodulatory drug in the treatment of refractory and relapsed multiple myeloma patients. Our aim was to investigate the efficacy and safety of pomalidomide therapy in a real world setting. Eighty-six Hungarian patients were included, 45 of whom received pomalidomide ± an alkylating agent, while in 38 of them pomalidomide was combined with a proteasome inhibitor. 56 patients (65%) showed any response to the treatment with 18 complete or very good partial remissions and 38 partial remissions. At a median duration of follow-up of 18.6 months, the median progression-free survival (PFS) was 9.03 months, while the median overall survival (OS) was 16.53 months in the whole cohort. Patients with early stage disease (R-ISS 1 and 2) had better survival results than those with stage 3 myeloma (p = 0.002). Neither the number of prior treatment lines, nor lenalidomide refractoriness had a significant impact on PFS. PFS was found similar between the cohort of patients with impaired renal function and the cohort without kidney involvement. During the study, eight mortal infections and two fatal bleeding complications occurred, however, mild hematologic and gastrointestinal toxicities were identified as the most frequent adverse events. The results of our investigations confirm that pomalidomide is an effective treatment option for relapsed/refractory MM, besides, the safety profile is satisfactory in subjects with both normal and impaired renal function.

Beneficial Effect of Lenalidomide-Dexamethason Treatment in Relapsed/Refractory Multiple Myeloma Patients: Results of Real-Life Data From 11 Hungarian Centers.

In Hungary, the cost of lenalidomide-based therapy is covered only for relapsed multiple myeloma (MM) patients, therefore lenalidomide is typically used in the second-line either as part of a triplet with proteasome inhibitors or as a doublet. Lenalidomide-dexamethasone is a standard treatment approach for relapsed/refractory MM, and according to recent large randomized clinical trials (RCT, the standard arm of POLLUX, ASPIRE, TOURMALINE), the progression-free survival (PFS) is expected to be approximately 18 months. We surveyed ten Hungarian centers treating MM and collected data of 278 patients treated predominantly after 2016. The median age was 65 years, and patients were distributed roughly equally over the 3 international staging system groups, but patients with high risk cytogenetics were underrepresented. 15.8% of the patients reached complete response, 21.6% very good partial response, 40.6% partial response, 10.8% stable disease, and 2.5% progressed on treatment. The median PFS was unexpectedly long, 24 months, however only 9 months in those with high risk cytogenetics. We found interesting differences between centers regarding corticosteroid type (prednisolone, methylprednisolone or dexamethasone) and dosing, and also regarding the choice of anticoagulation, but the outcome of the various centers were not different. Although the higher equivalent steroid dose resulted in more complete responses, the median PFS of those having lower corticosteroid dose and methylprednisolone were not inferior compared to the ones with higher dose dexamethasone. On multivariate analysis high risk cytogenetics and the number of prior lines remained significant independent prognostic factors regarding PFS (p < 0.001 and p = 0.005). Our results show that in well-selected patients Lenalidomide-dexamethasone can be a very effective treatment with real-world results that may even outperform those reported in the recent RCTs. This real world information may be more valuable than outdated RCT data when treatment options are discussed with patients.

Real-world data on the efficacy and safety of daratumumab treatment in Hungarian relapsed/refractory multiple myeloma patients.

Daratumumab is a human anti-CD38 monoclonal antibody used in the treatment of refractory and relapsed multiple myeloma. We investigated the efficacy and safety of daratumumab therapy in a real-world setting. Ninety-nine Hungarian patients were included; 48 received monotherapy, while lenalidomide and bortezomib combinations were administered in 29 and 19 cases, respectively. Overall response rate was assessable in 88 patients, with 12 complete, 10 very good partial, 34 partial, and seven minor responses. At a median duration of follow-up of 18.6 months, median progression-free survival (PFS) among all patients was 17.0 months. These values were inferior in the bortezomib combination and monotherapy groups. Patients with early-stage disease (ISS1) had better survival results than those with stage 2 or 3 myeloma (p = 0.009). Heavily pretreated patients had inferior PFS compared to those with 1-3 therapies (p = 0.035). Patients with impaired renal function had PFS results comparable with those having no kidney involvement. There were 10 fatal infections, and the most frequent adverse events were mild infusion-associated reactions and hematologic toxicities. Our results confirm that daratumumab is an effective treatment option for relapsed/refractory MM with an acceptable safety profile in patients with normal and impaired renal function.

Validity of the EQ-5D-5L and EQ-5D-3L in patients with Crohn's disease.

PURPOSE: The EuroQol five-dimension questionnaire (EQ-5D) is the most commonly used instrument to obtain utility values for cost-effectiveness analyses of treatments for Crohn's disease (CD). We aimed to compare the measurement properties of the two adult versions of EQ-5D (EQ-5D-3L and EQ-5D-5L) in patients with CD. METHODS: Between 2016 and 2017, a multicentre cross-sectional survey was carried out. Consecutive outpatients with CD completed the 3L, 5L and EQ visual analogue scale (VAS). Disease severity was graded by the Crohn's Disease Activity Index (CDAI) and Perianal Disease Activity Index (PDAI). The 3L and 5L were compared in terms of feasibility, agreement, ceiling effect, redistribution properties, discriminatory power, convergent and known-groups validity. RESULTS: Two-hundred and six patients (54.9% male, mean age 35 ± 11 years) participated in the survey. For 3L, 25 unique health states were observed versus 59 for the 5L. The overall ceiling effect decreased from 29.6% (3L) to 25.5% (5L). Absolute discriminatory power improved (mean Shannon index 0.84 vs. 1.18). The 3L correlated stronger with EQ VAS and CDAI scores, whereas the 5L with PDAI. The 5L demonstrated a better known-groups validity on the basis of age, perianal fistulas, extraintestinal manifestations and disability. CONCLUSIONS: This is the first study to report the impact of CD on quality of life using the EQ-5D-5L questionnaire. The 5L seems to perform better than 3L in terms of feasibility, ceiling effect, discriminatory power and known-groups validity. Understanding the differences in psychometrics between the 3L and 5L is essential as they have substantial implications for financial decision-making about CD treatments.

Infliximab biosimilar CT-P13 therapy is effective in maintaining endoscopic remission in ulcerative colitis - results from multicenter observational cohort.

BACKGROUND: CT-P13, the first biosimilar monoclonal antibody to infliximab (IFX), has previously been confirmed to be efficacious in inducing mucosal healing in ulcerative colitis (UC) patients. The aim of this study was to evaluate the efficacy of CT-P13 therapy in maintaining mucosal healing in UC. METHODS: CT-P13 trough levels, antibody positivity, serum inflammatory markers as CRP level, fecal calprotectin at weeks 14 and 54, concomitant steroid and azathioprine therapy at the time of induction therapy and at weeks 14 and 54, previous use of anti TNF drug and the need of dose intensification as possible predictive factors for mucosal healing at week 54 were evaluated in this prospective study. RESULTS: 61 patients had already completed the 54-week treatment period. Mucosal healing was shown in 65.5 % and 62.1 %, complete mucosal healing was present in 31% and 38 % at week 14 and 54, respectively. The median values of CRP, leukocytes, thrombocytes, and albumin showed significant difference between baseline and week 54. Serum antibody positivity was proved in 6.5 % and 19.7 % of cases at week 14 and 54, respectively. CONCLUSION: Our study confirmed the long-term efficacy of CT-P13 therapy on mucosal healing in UC.

The potential role of FDG PET-CT in the characterization of the activity of Crohn's disease, staging follow-up and prognosis estimation: a pilot study.

OBJECTIVES: FDG PET-CT is a global, noninvasive, sensitive method to determine the location and activity of inflammatory lesions. Segmental FDG uptake is proportional with immune cell infiltration of bowel. Our aim was to evaluate prospectively the role of PET in patients with active Crohn's disease (CD) before and after one year's biological therapy, and to compare simple endoscopic score for CD (SES-CD), CD activity index (CDAI) and global PET scores. We also analyzed the prognostic value of initial PET scores. PATIENTS: Twelve patients were selected: six male/six female, ages between 18 and 39, average: 24 years, with CDAI values >300. METHODS: We scored the FDG uptake in the small intestine and the four colon segments (on a scale 0-3 for each), and summed them thus forming a global PET score. The scoring was based on the maximal standardized uptake value of the intestinal segment, related to the SUVmax of the liver (as a reference for normal tissue activity). The SES-CD, CDAI and global PET scores before and after treatment were statistically compared. RESULTS: There were significant changes in CDAI and SES-CD after therapy, PET scores improved only in patients' subgroup with high (>4) initial PET score, indicating good prognosis of biological treatment. In active disease, PET was more informative than endoscopy to access the extent of the inflammation, and small intestine involvement. CONCLUSIONS: FDG PET-CT score is a promising, noninvasive complementary method in the staging, treatment planning and follow-up of CD. Limitation of the study is the small number of patients.