Using a specialized orthopedic software package, the authors investigated the sagittal spinal shape and the position of the pelvis in the space in patients with isthmic spondylolisthesis and in persons with no such symptoms. Digitized lateral spinal radiographs of 30 healthy volunteers and 48 patients were evaluated. The absolute values and significant correlations between parameters were analyzed. The pelvic parameters correlated well with lordosis, which shows sagittal balance in the asymptomatic group. The hyperlordosis and the horizontally positioned sacrum in isthmic spondylolisthesis enlarge the tensile force component of gravity, which may cause the lysis. Finally, the authors developed a new balance between the pelvis and the spine after slipping of the vertebral body. The degree of slipping correlated well with the sacrofemoral anatomic constant (incidence), which is unique in each person.
Carfilzomib, a proteasome inhibitor, is approved as monotherapy and in combination with dexamethasone or lenalidomide–dexamethasone (Rd) for relapsed or refractory multiple myeloma. The approval of carfilzomib–lenalidomide–dexamethasone (KRd) was based on results from the randomized, phase 3 study ASPIRE (NCT01080391), which showed KRd significantly improved progression-free survival (PFS) vs Rd (median 26.3 vs 17.6 months; hazard ratio (HR)=0.690; P=0.0001). This subgroup analysis of ASPIRE evaluated KRd vs Rd by number of previous lines of therapy and previous exposure to bortezomib, thalidomide or lenalidomide. Treatment with KRd led to a 12-month improvement in median PFS vs Rd after first relapse (HR 0.713) and a 9-month improvement after ⩾2 previous lines of therapy (HR 0.720). Treatment with KRd led to an approximate 8-month improvement vs Rd in median PFS in bortezomib-exposed patients (HR 0.699), a 15-month improvement in thalidomide-exposed patients (HR 0.587) and a 5-month improvement in lenalidomide-exposed patients (HR 0.796). Objective response and complete response or better rates were higher with KRd vs Rd, irrespective of previous treatment. KRd had a favorable benefit–risk profile and should be considered an appropriate treatment option for patients with 1 or ⩾2 previous lines of therapy and those previously exposed to bortezomib, thalidomide or lenalidomide.
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.
SummaryA primary analysis of the ASPIRE study found that the addition of carfilzomib to lenalidomide and dexamethasone (carfilzomib group) significantly improved progression‐free survival (PFS) compared with lenalidomide and dexamethasone alone (control group) in patients with relapsed multiple myeloma (RMM). This post hoc analysis examined outcomes from ASPIRE in patients categorised by age. In the carfilzomib group, 103/396 patients were ≥70 years old, and in the control group, 115/396 patients were ≥70 years old. Median PFS for patients <70 years old was 28·6 months for the carfilzomib group versus 17·6 months for the control group [hazard ratio (HR), 0·701]. Median PFS for patients ≥70 years old was 23·8 months for the carfilzomib group versus 16·0 months for the control group (HR, 0·753). For patients <70 years the overall response rate (ORR) was 86·0% (carfilzomib group) and 66·9% (control group); for patients ≥70 years old the ORR was 90·3% (carfilzomib group) and 66·1% (control group). Within the carfilzomib group, grade ≥3 cardiovascular adverse events occurred more frequently among patients ≥70 years old compared with patients <70 years old. Carfilzomib‐lenalidomide‐dexamethasone has a favourable benefit‐risk profile for patients with RMM, including elderly patients ≥70 years old. Trial Registration: clinicaltrials.gov identifier: NCT01080391.
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