ASH Clinical News ACN_4.13_full issue_Web | Page 32

Written in Blood Risk of Thrombosis in Patients With Cancer and Implanted Ports Although patients with solid-tumor cancers and implanted ports have a high risk for venous thromboembolism (VTE), guidelines advise against routine thromboprophylaxis, given the wide variation in thrombotic risks in this setting. In results from a prospective cohort study published in Blood, researchers determined risk factors associated with thromboembolic events in this patient population that could help identify patients who would benefit from thromboprophylaxis. Specifically, the use of the cephalic vein for catheter insertion was a substantial risk factor for catheter- related thrombosis, but not for non– catheter-related thrombosis. “That risk factors for catheter- related thrombosis differ from those for VTE unrelated to the catheter was an unexpected finding and may have clinical implications,” the authors, led by Hervé Decousus, MD, of the Cen- tre d’Investigation Clinique, in Saint- Etienne, France, wrote. Data from this real-world study may help risk-stratify patients and guide decisions about catheter insertion site and antiplatelet or anticoagulant therapy. To identify risk factors for catheter-related thrombosis and non– catheter-related VTE in patients with an implanted port, the ONCOCIP (ONCOlogie et Chambres ImPlant- ables) study included 3,032 adult patients (median age = 63 years; range not reported) from 29 French medi- cal centers. The most common cancer sites were breast (33.7%), lung (18.5%), and colon (15.6%), and 43.2 percent of patients had metastatic cancer. Nearly all patients (97.1%) received chemo- therapy. Follow-up consisted of in-person, face-to-face visits every month for up to six months, then every three months for up to 12 months (or until death or port removal). Participants were directed to report to the study center immediately if any signs or symptoms occurred, including any thromboembolic event, infection, or local port-related complication. At 12-month follow-up, 656 pa- tients (21.6%) had died, and 48 (1.6%) were lost to follow-up. Another 479 patients (15.8%) discontinued the study prematurely due to definitive port removal. Overall, thrombosis occurred in 397 patients (13.8%), including: • catheter-related thrombosis: 111 patients (3.8%) • non–catheter-related VTE: 276 patients (9.6%) 30 ASH Clinical News Catheter-related thrombosis included 106 patients (3.8%) who developed an upper- extremity deep vein thrombosis and five patients (0.2%) who developed a pulmo- nary embolism associated with upper- extremity deep vein thrombosis. The median time to any symptomatic catheter-related thrombosis was 45 days (range = 23-99 days). In addition, of the 397 patients who experienced a throm- boembolic event, 329 (82.9%) received anticoagulation at therapeutic dose. In multivariate analyses, use of the cephalic vein for catheter insertion was the only risk factor significantly and independently associated with 12-month catheter-related thrombosis (hazard ratio [HR] = 2.51; 95% CI 1.68-3.75; p<0.0001). Conversely, ongoing use of antiplatelet therapy at baseline had a protective effect and was independently associated with a reduced risk of catheter-related throm- bosis at 12 months (HR=0.44; 95% CI 0.21-0.90; p=0.024). However, neither of these risk factors were associated with rates of non–catheter- related VTE at 12 months. The researchers NOW APPROVED The FIRST AND ONLY oral dual PI3K-δ and PI3K-γ inhibitor that targets malignant B cells and the tumor microenvironment. 1,2 COPIKTRA is a kinase inhibitor indicated for the treatment of adult patients with 1 : • Relapsed or refractory CLL or SLL after at least 2 prior therapies • Relapsed or refractory FL after at least 2 prior systemic therapies This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. VISIT COPIKTRAHCP.COM/NOWAPPROVED FOR MORE INFORMATION CLL, chronic lymphocytic leukemia; FL, follicular lymphoma; PI3K, phosphoinositide 3-kinase; SLL, small lymphocytic lymphoma. IMPORTANT SAFETY INFORMATION WARNING: FATAL AND SERIOUS TOXICITIES: INFECTIONS, DIARRHEA OR COLITIS, CUTANEOUS REACTIONS, and PNEUMONITIS • Fatal and/or serious infections occurred in 31% of COPIKTRA-treated patients. Monitor for signs and symptoms of infection. Withhold COPIKTRA if infection is suspected. • Fatal and/or serious diarrhea or colitis occurred in 18% of COPIKTRA-treated patients. Monitor for the development of severe diarrhea or colitis. Withhold COPIKTRA. • Fatal and/or serious cutaneous reactions occurred in 5% of COPIKTRA-treated patients. Withhold COPIKTRA. • Fatal and/or serious pneumonitis occurred in 5% of COPIKTRA-treated patients. Monitor for pulmonary symptoms and interstitial infiltrates. Withhold COPIKTRA. WARNINGS AND PRECAUTIONS Infections: Serious, including fatal (18/442; 4%), infections occurred in 31% of patients receiving COPIKTRA 25 mg BID (N=442). The most common serious infections were pneumonia, sepsis, and lower respiratory infections. Median time to onset of any grade infection was 3 months (range: 1 day to 32 months), with 75% of cases occurring within 6 months. Treat infections prior to initiation of COPIKTRA. Advise patients to report new or worsening signs and symptoms of infection. For grade 3 or higher infection, withhold COPIKTRA until infection is resolved. Resume COPIKTRA at the same or reduced dose. Serious, including fatal, Pneumocystis jirovecii pneumonia (PJP) occurred in 1% of patients taking COPIKTRA. Provide prophylaxis for PJP during treatment with COPIKTRA and following completion of treatment with COPIKTRA until the absolute CD4+ T cell count is greater than 200 cells/µL. Withhold COPIKTRA in patients with suspected PJP of any grade, and permanently discontinue if PJP is confirmed. Cytomegalovirus (CMV) reactivation/infection occurred in 1% of patients taking COPIKTRA. Consider prophylactic antivirals during COPIKTRA treatment to prevent CMV infection including CMV reactivation. For clinical CMV infection or viremia, withhold COPIKTRA until infection or viremia resolves. If COPIKTRA is resumed, administer the same or reduced dose and monitor patients for CMV reactivation by PCR or antigen test at least monthly. Diarrhea or Colitis: Serious, including fatal (1/442; <1%), diarrhea or colitis occurred in 18% of patients receiving COPIKTRA 25 mg BID (N=442). Median time to onset of any grade diarrhea or colitis was 4 months (range: 1 day to 33 months), with 75% of cases occurring by 8 months. The median event duration was 0.5 months (range: 1 day to 29 months; 75 th percentile: 1 month). Advise patients to report any new or worsening diarrhea. For patients presenting with mild or moderate diarrhea (Grade 1-2) (i.e., up to 6 stools per day over baseline) or asymptomatic (Grade 1) colitis, initiate supportive care with antidiarrheal agents, continue COPIKTRA at the current dose, and monitor the patient at least weekly until the event resolves. If the diarrhea is unresponsive to antidiarrheal therapy, withhold COPIKTRA and initiate supportive therapy with enteric acting steroids (e.g., budesonide). Monitor the patient at least weekly. Upon resolution of the diarrhea, consider restarting COPIKTRA at a reduced dose. For patients presenting with abdominal pain, stool with mucus or blood, change in bowel habits, peritoneal signs, or with severe diarrhea (Grade 3) (i.e., > 6 stools per day over baseline), withhold COPIKTRA and initiate supportive therapy with enteric acting steroids (e.g., budesonide) or systemic steroids. A diagnostic work-up to determine etiology, including colonoscopy, should be performed. Monitor at least weekly. Upon resolution of the diarrhea or colitis, restart COPIKTRA at a reduced dose. For recurrent Grade 3 diarrhea or recurrent colitis of any grade, discontinue COPIKTRA. Discontinue COPIKTRA for life-threatening diarrhea or colitis. Cutaneous Reactions: Serious, including fatal (2/442; <1%), cutaneous reactions occurred in 5% of patients receiving COPIKTRA 25 mg BID (N=442). Fatal cases included drug reaction with eosinophilia and systemic symptoms (DRESS) and toxic epidermal necrolysis (TEN). Median time to onset of any grade cutaneous reaction was 3 months (range: 1 day to 29 months, 75 th percentile: 6 months) with a median event duration of 1 month (range: 1 day to 37 months, 75 th percentile: 2 months). Presenting features for the serious events were primarily described as pruritic, erythematous, or maculo-papular. Less common presenting features include exanthem, desquamation, erythroderma, skin exfoliation, keratinocyte necrosis, and papular rash. Advise patients to report new or worsening cutaneous reactions. Review all concomitant medications and discontinue any medications potentially contributing to the event. For patients presenting with