Publications

This phase 1b, open-label, dose-escalation study assessed the safety, efficacy, and pharmacokinetics of anti-CD38 monoclonal antibody isatuximab given in 2 schedules (3, 5, or 10 mg/kg every other week [Q2W] or 10 or 20 mg/kg weekly [QW] for 4 weeks and then Q2W thereafter [QW/Q2W]), in combination with lenalidomide 25 mg (days 1-21) and dexamethasone 40 mg (QW), in patients with relapsed/refractory multiple myeloma (RRMM). Patients received 28-day treatment cycles; the primary objective was to determine the maximum tolerated dose (MTD) of isatuximab with lenalidomide and dexamethasone. Fifty-seven patients (median 5 [range 1-12] prior regimens; 83% refractory to previous lenalidomide therapy) were treated. Median duration of dosing was 36.4 weeks; 15 patients remained on treatment at data cutoff. Isatuximab-lenalidomide-dexamethasone was generally well tolerated with only 1 dose-limiting toxicity reported (grade 3 pneumonia at 20 mg/kg QW/Q2W); the MTD was not reached. The most common isatuximab-related adverse events were infusion-associated reactions (IARs) (56%), which were grade 1/2 in 84% of patients who had an IAR and predominantly occurred during the first infusion. In the efficacy-evaluable population, the overall response rate (ORR) was 56% (29/52) and was similar between the 10 mg/kg Q2W and 10 and 20 mg/kg QW/Q2W cohorts. The ORR was 52% in 42 evaluable lenalidomide-refractory patients. Overall median progression-free survival was 8.5 months. Isatuximab exposure increased in a greater than dose-proportional manner; isatuximab and lenalidomide pharmacokinetic parameters appeared independent. These data suggest that isatuximab combined with lenalidomide and dexamethasone is active and tolerated in heavily pretreated patients with RRMM. This trial was registered at www.clinicaltrials.gov as #NCT01749969.

BACKGROUND

Despite their well-recognised shortcomings, haemodialysis catheters (HDCs) remain an important form of haemodialysis access for many patients. There are several HDCs commercially available, each differing considerably in design, which is known to significantly influence performance and survival. We sought to determine which of two tunnelled HDCs, DuraMax® (Angiodynamics, NY, USA) or SplitCath® (MedComp, PA, USA) delivers the best performance, safety and reliability for dialysis patients.

METHODS

Eighty-six patients were prospectively randomised to receive either DuraMax® (DM) or SplitCath® (SC). Outcomes included: (i) mean flow rates (mL/min) averaged over the first 10 weeks of dialysis, and urea reduction ratio (URR); and (ii) long-term catheter survival with appraisal of any events leading to catheter dysfunction and early removal.

RESULTS

Median flow rates (interquartile range) in the DM and SC groups were 321 (309-343) and 309 (294-322) mL/min, respectively (p = 0.002). URR values for the DM and SC groups were 71 (65-76) and 74 (70-78), respectively, (p = 0.094). There was no significant difference in long-term survival or frequency of incidents that required early HDC removal (9/43 in the DM group, 5/43 patients SC). A slightly higher incidence of HDC dislodgement was noted in the DM group, although this study was not statistically powered to determine its significance.

CONCLUSIONS

We conclude that DM yields slightly higher flow rates in the first 10 weeks of dialysis, and a similar low incidence of complications and long-term survival for both DM and SC HDCs.