Pulmonary embolism (PE) represents a serious cause of morbidity and mortality, particularly in hospitalized patients. It is estimated that PE leads to more than 200 000 deaths annually in the United States.¹ For these patients and those at risk for PE, anticoagulant therapy remains the standard of care.² If the patient has a contraindication to anticoagulants, an inferior vena cava (IVC) filter is often considered. The concept of surgical vena cava interruption was first introduced in 1865 by Trousseau.³ Surgical insertion of IVC filters was pioneered in the 1960s but was used infrequently until the development of the percutaneous IVC filter insertion technique in 1973 by Greenfield.⁴ The arrival of retrievable devices in the 1990s facilitated potential removal of IVC filters.⁵

To identify the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in patients with transthyretin (ATTR) amyloidosis. We performed a retrospective analysis of patients with biopsy-proven ATTRwt (wild-type transthyretin amyloid protein) and genopositive ATTR V122I (valine-to-isoleucine substitution at position 122 of the TTR gene) amyloidosis evaluated at the Amyloidosis Center at Boston University and Boston Medical Center between 1 January 2003 and 31 December 2016. There were a total of 226 patients with ATTRwt and ATTR V122I amyloidosis evaluated during the specified time frame with 155 and 71 patients in each cohort, respectively. Those with complete medical records, 140 patients with ATTRwt and 57 V1221 ATTRm subjects, were included in the analyses. Fifty-five patients (39%) in the ATTRwt cohort and 28 patients (49%) in the ATTR V122I cohort had an MGUS, as indicated by an abnormality in the serum-free light-chain ratio and/or serum immunofixation electrophoresis. These data confirm the high prevalence of coexistent MGUS with ATTR amyloidosis in this patient population, with an MGUS rate that is higher than the general population. These findings also highlight the importance of a thorough diagnostic evaluation in patients with amyloidosis to determine the precursor protein, as the clinical course and treatment of AL (light-chain amyloid protein) and ATTR amyloidosis are distinct.

Daratumumab, a monoclonal CD38 antibody, is approved in the treatment of myeloma, but its efficacy and safety in light-chain (AL) amyloidosis has not been formally studied. This prospective phase 2 trial of daratumumab monotherapy for the treatment of AL amyloidosis was designed to determine the safety, tolerability, and hematologic and clinical response. Daratumumab 16 mg/kg was administered by IV infusion once weekly for weeks 1 to 8, every 2 weeks for weeks 9 to 24, and every 4 weeks thereafter until progression or unacceptable toxicity, for up to 24 months. Twenty-two patients with previously treated AL amyloidosis were enrolled. The majority of the patients had received high-dose melphalan and stem cell transplantation and/or treatment with a proteasome inhibitor. The median time between prior therapy and trial enrollment was 9 months (range, 1-180 months). No grade 3-4 infusion-related reactions occurred. The most common grade ≥3 adverse events included respiratory infections (n = 4; 18%) and atrial fibrillation (n = 4, 18%). Hematologic complete and very-good-partial response occurred in 86% of patients. The median time to first and best hematologic response was 4 weeks and 3 months, respectively. Renal response occurred in 10 of 15 patients (67%) with renal involvement and cardiac response occurred in 7 of 14 patients (50%) with cardiac involvement. In summary, daratumumab is well tolerated in patients with relapsed AL amyloidosis and leads to rapid and deep hematologic responses and organ responses. This trial was registered at www.clinicaltrials.gov as #NCT02841033.

PURPOSE: BCL2 is overexpressed and confers prosurvival signaling in malignant lymphoplasmacytic cells in Waldenström macroglobulinemia (WM). Venetoclax is a potent BCL2 antagonist and triggers in vitro apoptosis of WM cells. The activity of venetoclax in WM remains to be clarified. PATIENTS AND METHODS: We performed a multicenter, prospective phase II study of venetoclax in patients with previously treated WM ( NCT02677324 ). Venetoclax was dose-escalated from 200 mg to a maximum dose of 800 mg daily for up to 2 years. RESULTS: Thirty-two patients were evaluable, including 16 previously exposed to Bruton tyrosine kinase inhibitors (BTKis). All patients were MYD88 L265P–mutated, and 17 carried CXCR4 mutations. The median time to minor and major responses was 1.9 and 5.1 months, respectively. Previous exposure to BTKis was associated with a longer time to response (4.5 v 1.4 months; P < .001). The overall, major, and very good partial response rates were 84%, 81%, and 19%, respectively. The major response rate was lower in those with refractory versus relapsed disease (50% v 95%; P = .007). The median follow-up time was 33 months, and the median progression-free survival was 30 months. CXCR4 mutations did not affect treatment response or progression-free survival. The only recurring grade ≥ 3 treatment-related adverse event was neutropenia (n = 14; 45%), including one episode of febrile neutropenia. Laboratory tumor lysis without clinical sequelae occurred in one patient. No deaths have occurred. CONCLUSION: Venetoclax is safe and highly active in patients with previously treated WM, including those who previously received BTKis. CXCR4 mutation status did not affect treatment response.

Herein, we present the final report of a single-center, prospective phase II study evaluating ibrutinib 420 mg once daily in 30 treatment-naive patients with Waldenstrom macroglobulinemia (WM). The present study is registered with ClinicalTrials.Gov (NCT02604511). With a median follow-up of 50 months, the overall, major, and VGPR response rates were 100%, 87%, and 30%. The VGPR rate was numerically but not significantly lower in patients with than without CXCR4 mutations (14% vs. 44%; p = 0.09). The median time to a minor response was 0.9 months, and to a major response was 1.9 months, though were longer in those with mutated CXCR4 at 1.7 months (p = 0.07) and 7.3 months (p = 0.01). Six patients had disease progression. The median progression-free survival (PFS) was not reached, and the 4-year PFS rate was 76%. There was also a non-significant lower 4-year PFS rate in patients with than without CXCR4 mutations (59% vs. 92%; p = 0.06). The most common treatment-related adverse events were fatigue, upper respiratory infection, and hematoma. Atrial fibrillation occurred in 20% of patients. Ibrutinib monotherapy induced durable responses in treatment-naive patients with WM. CXCR4 mutations impacted VGPR attainment, time to major response, and 4-year PFS rate.

Despite achieving a hematologic complete response after treatment, many patients with AL amyloidosis do not attain recovery of organ function and/or experience hematologic relapse. A persistent plasma cell clone producing amyloidogenic light chains at levels below the detection threshold of traditional serologic methods is hypothesized to impede organ response in some patients. Assessment of minimal residual disease (MRD) may therefore have clinical importance as a more stringent treatment response tool for patients in a hematologic complete response. We used 2-tube, 10-color combination multiparametric flow cytometry to assess for MRD at a minimum sensitivity of 1 in 105 nucleated cells. Of 65 patients in hematologic complete response, 36 (55%) were found to have a residual clonal plasma cell population in the bone marrow. Comparing the MRD-negative and MRD-positive groups, renal response was observed in 88% vs 64% (P = .06), cardiac response in 75% vs 59% (P = .45), and any organ response in 90% vs 75% (P = .20) of patients. Depth of organ response as measured by the percent decrease in 24-hour proteinuria and brain natriuretic peptide was 96% vs 91% (P = .16) and 55% vs 46% (P = .66), respectively. These data suggest a possible correlation between MRD negativity and higher probability of organ response after treatment in AL amyloidosis. Future prospective studies with a larger cohort are needed to determine the clinical relevance of these improvements. This trial was registered at www.clinicaltrials.gov as #NCT00898235.