ASH Clinical News March 2015 | Page 24

Written in Blood Low-Molecular-Weight Heparin Fails to Boost Live Birth Rates in Women with Recurrent Miscarriage percent of the enoxaparin group and 23.7 percent of the placebo group had another miscarriage (RR = 1.28, 95% CI 0.85 to 1.93), with the majority (84.3%) occurring before ten weeks’ gestation. “Prophylactic doses of LMWH do not improve the chance of a live birth in nonthrombophilic women with unexplained recurrent miscarriage and should consequently no longer be routinely prescribed in this clinical setting,” the researchers stated. Asked if aspirin may prove more effective in this patient population, Dr. Pasquier explained that the Scottish Pregnancy Intervention (SPIN) study, which assessed LWMH and low-dose aspirin in women with recurrent miscarriage, “showed no efficacy of openlabel LMWH plus aspirin versus intense pregnancy surveillance alone.” Antithrombotic medications are often prescribed to women with histories of unexplained recurrent miscarriages , although there is little evidence of the efficacy of this approach. But the use of low-molecular-weight heparin (LMWH) in non-thrombophilic women with unexplained recurrent miscarriages did not improve live birth rates, according to a report in Blood. Given these results, clinicians should stop prescribing LMWH in this particular patient population, lead investigator Elisabeth Pasquier, MD, of Brest University Hospital in Brest, France, told ASH Clinical News. N O W AVA I L A B L E The theory that women with recurrent miscarriages and negative tests F O R T H E T R E A T M E N T O F P h - N E G A T I V E R E L A P S E D / R E F R A C T O RY for antiphospholipid antibodies (or B - C E L L A C U T E LY M P H O B L A S T I C L E U K E M I A ( A L L ) negative tests for inherited thrombophilia) may have some other blood clotting disorder resulted in the use of LMWH therapy among these patients, Dr. Pasquier explained. Dr. Pasquier and colleagues conducted a randomized, double-blind, placebo-controlled trial of enoxaparin in 256 women with a history Discover the first and only FDA-approved Bispecific CD19-directed CD3 T-cell Engager of two or more consecutive miscarriages before 15 weeks gestation and In a phase 2, open-label, multicenter, a negative thrombophilia work-up single-arm clinical trial: at 13 French hospital centers from April 2007 to October 2012. About (95% CI: 64.2-84.4) • The primary endpoint was the complete 70 percent of the women had three or remission/complete remission with partial with CR/CRh* also had an hematological recovery (CR/CRh*) rate more consecutive miscarriages. MRD response (defined within 2 cycles of treatment with BLINCYTO™. Most of the patients were early as MRD by PCR < 1 x 10-4) in their pregnancy, between 5 to • Eligible patients were ≥ 18 years of age with (n=58/77)1 (95% CI: 34.4-49.1) Philadelphia chromosome-negative relapsed 6 weeks’ gestation, at the time of of R/R ALL evaluable or refractory B-precursor ALL. study enrollment. After training patients achieved a • Relapsed or refractory was defined as relapsed for self-injection, the participants with first remission duration of ≤ 12 months CR/CRh* (n=77/185)1 were randomly assigned to receive of patients who achieved in first salvage or relapsed or refractory after enoxaparin 40 mg or saline-solution CR/CRh* went on to receive first salvage therapy or relapsed within placebo daily. Baseline characteristics allogeneic transplant 12 months of allogeneic hematopoietic stem were similar among the groups. (n=30/77)1 cell transplantation (HSCT), and had ≥ 10% Therapy began on the enrollment blasts in bone marrow. visit and continued until 35 weeks’ gestation. Patients maintained a log INDICATION of their injection site and treatment BLINCYTO™ is indicated for the treatment of Philadelphia chromosome-negative relapsed or refractory B-cell precursor time on a daily basis to ensure protoacute lymphoblastic leukemia (ALL). col compliance. Nearly 70 percent of all women in This indication is approved under accelerated approval. Continued approval for this indication may be contingent upon the study had a live and viable birth, verification of clinical benefit in subsequent trials. the study’s primary outcome: 66.6 IMPORTANT SAFETY INFORMATION percent of the enoxaparin patients and 72.9 percent of the placebo WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES patients. • Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving The rates of live and viable births BLINCYTO™. Interrupt or discontinue BLINCYTO™ as recommended. did not differ significantly between • Neurological toxicities, which may be severe, life-threatening or fatal, occurred in patients receiving BLINCYTO™. groups (absolute difference in liveInterrupt or discontinue BLINCYTO™ as recommended. birth rates = –6% [95% CI −17.1 to 5.1; p = 0.34]), the researchers noted. Contraindications There were also no significant differBLINCYTO™ is contraindicated in patients with a known hypersensitivity to blinatumomab or to any component of the ences in secondary outcomes (rates product formulation. of miscarriage, obstetric complications, maternal thrombocytopenia, Warnings and Precautions bleeding episodes, and skin reaction) • Cytokine Release Syndrome (CRS): Life-threatening or fatal CRS occurred in patients receiving BLINCYTO™. Infusion among the groups. reactions have occurred and may be clinically indistinguishable from manifestations of CRS. Closely monitor patients Over the course of the study, 30.4 75.3% 41.6% 39% for signs and symptoms of serious events such as pyrexia, headache, nausea, asthenia, hypotension, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased total bilirubin (TBILI), disseminated intravascular coagulation (DIC), capillary leak syndrome (CLS), and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS). Interrupt or discontinue BLINCYTO™ as outlined in the Prescribing Information (PI). 20 ASH Clinical News