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At the time of data cutoff , median durations of treatment were 80 weeks for the isatuximab group and 61.4 weeks for the control regimen . Both groups received a similar median relative dose intensity of Kd during the study period .
Median PFS was not reached at follow-up for the isatuximab plus Kd arm , while the median PFS for the Kd group was 19.2 months ( 95 % CI 15.77 to not reached ). The interim analysis revealed that the addition of isatuximab led to a significantly prolonged PFS compared with only Kd ( hazard ratio [ HR ] = 0.53 ; 99 % CI 0.32 – 0.89 ; p = 0.0007 ).
The two-year estimated PFS was 68.9 % for the isatuximab arm compared with 45.7 % for the control group ( HR = 0.58 ; 99 % CI 0.36 – 0.92 ; p = 0.0010 ).
In the intention-to-treat cohort , most patients in the isatuximab group and the control group experienced an overall response ( 87 % vs . 83 %, respectively ; p = 0.19 ). A significantly greater proportion of patients assigned to isatuximab experienced a very good partial response or better ( 73 % vs . 56 %; p = 0.0011 ). A higher proportion of patients treated with isatuximab also had a complete response : 40 % vs . 28 %.
The measurable residual disease negativity rate was significantly greater in patients treated with isatuximab versus those treated with only Kd ( 30 % vs . 13 %; p = 0.0004 ).
Approximately 77 % of patients in the isatuximab arm and 67 % of patients in the control group experienced grade ≥3 treatment-emergent adverse events ( TEAEs ). Serious TEAEs were reported in 59 % of patients randomized to isatuximab compared with 57 % patients assigned to Kd .
In addition , 8 % of patients in the isatuximab combination group and 14 % of patients in the control group experienced TEAEs , which led to treatment discontinuation . Up to 3 % of patients in each group experienced fatal TEAEs during the study .
One limitation of this study was the low prevalence of Black patients ( 3 %), mostly because of lower recruitment at U . S . -based sites . The researchers stated that evidence shows these patients derive nearly the same benefits from proteasome inhibitors as patients who are white .
Study authors report relationships with Sanofi , which sponsored this trial .
Reference Moreau P , Dimopoulos MA , Mikhael J , et al . Isatuximab , carfilzomib , and dexamethasone in relapsed multiple myeloma ( IKEMA ): a multicentre , open-label , randomised phase III trial . Lancet Haematol . 2021 ; 397:2361-2371 .
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Comparing VTE Recurrence , Bleeding , and Death in Isolated Distal Versus Proximal DVT
Patients with isolated distal deep-vein thrombosis ( DVT ) and proximal DVT have similar longterm rates of venous thromboembolism ( VTE ) recurrence , bleeding , and death , according to an analysis of real-world data published in the Journal of Thrombosis and Haemostasis . Treatment with direct oral anticoagulants ( DOACs ) was associated with lower rates of VTE recurrence , major bleeding , and mortality in these patients .
Approximately 70 % of acute VTE events in the U . S . involve deep veins in the lower extremities . Lower extremity DVT is divided into two categories based on proximal extent of the thrombosis : isolated distal DVT and proximal DVT .
Currently , the management of isolated distal DVT varies across centers , given its high prevalence . In addition , there are limited data available to guide clinicians on appropriate management strategies , anticoagulation intensity , and duration of treatment for patients with this form of DVT .
To gauge the clinical outcomes of patients with isolated distal DVT versus patients with proximal DVT , Robert McBane , MD , of Mayo Clinic , and researchers evaluated rates of recurrent VTE , major and clinically relevant nonmajor bleeding , and death in consecutive patients with confirmed acute DVT from the Mayo Clinic Gonda Vascular Center Ultrasound and VTE Registry databases .
Patients were stratified into two groups based on DVT location :
• isolated distal DVT ( n = 746 )
• proximal DVT ( n = 1,176 )
Patients were also divided based on the type of anticoagulant used ( low-molecular weight heparin vs . DOAC ).
Average age in the isolated distal DVT and proximal DVT groups was 62.4 ± 14.7 years and 62.8 ± 14.1 years , respectively . Individuals in the isolated distal DVT group had thrombus at either the axial or muscular venous segments , or both . In contrast , patients with proximal DVT had acute thrombus that involved the popliteal , femoral , or iliac veins .
At baseline , a significantly higher proportion of patients in the proximal DVT group had unprovoked events ( 24.8 % vs . 10.6 %; p < 0.001 ) and a prior history of VTE ( 28.1 % vs . 20.2 %; p < 0.001 ).
The investigators assessed rates of VTE recurrence , major bleeding , and death within and between the DVT and anticoagulant groups .
Respectively , the average follow-up periods for the VTE Registry and Calf DVT Registry were 8.6 ± 10.0 months and 11.1 ± 9.4 months . Over follow-up , the rates of VTE recurrence were similar between the isolated distal DVT group ( 4.60 per 100 person-years ) and the proximal DVT group ( 5.77 per 100 person-years ; p = 0.336 ).
At three months , mortality rates were significantly higher in patients with isolated distal DVT ( 7.2 % vs . 3.9 %; p = 0.001 ), but the difference did not last beyond this period .
A total of 440 patients with isolated distal DVT and 755 patients with proximal DVT used
Patients with isolated distal and proximal DVT have similar long-term rates of VTE recurrence , bleeding , and death .
DOACs . In this pooled subgroup , patients with isolated distal DVT had a significantly lower VTE recurrence rate ( 0.9 % vs . 3.0 %; p = 0.03 ). Treatment with DOACs in both groups was associated with more favorable rates of VTE recurrence , major bleeding , and death .
Patients with proximal DVT were more likely to have active cancer ( 39.5 % vs . 29.8 %; p < 0.001 ). In contrast , patients with isolated distal DVT more often had major trauma ( 15 % vs . 6.4 %; p < 0.001 ), recent surgery ( 34 % vs . 17.3 %; p < 0.001 ), or confinement ( 39 % vs . 19 %; p < 0.001 ).
Multivariable modeling revealed warfarin use ( vs . DOAC ), increasing age , and active cancer were independent predictors of mortality .
This study is limited by its retrospective design . In addition , the inclusion of patients from only a tertiary care setting may limit the generalizability of the findings .
The authors report no relevant conflicts of interest .
Reference Vlazny DT , Pasha AK , Kuczmik W , et al . Outcome of anticoagulation in isolated distal deep vein thrombosis compared to proximal deep venous thrombosis [ published online ahead of print , 2021 Jun 1 ]. J Thromb Haemost . doi : 10.1111 / jth . 15416 .
28 ASH Clinical News August 2021