Prophylaxis with intrathecal or high-dose methotrexate in diffuse large B-cell lymphoma and high risk of CNS relapse

Limfoma de cèl·lules B; Supervivència lliure de malaltiaLinfoma de células B; Supervivencia libre de enfermedadB-cell lymphoma; Disease-free survivalAlthough methotrexate (MTX) is the most widely used therapy for central nervous system (CNS) prophylaxis in patients with diffuse large B-cell lymphoma (DLBCL), the optimal regimen remains unclear. We examined the efficacy of different prophylactic regimens in 585 patients with newly diagnosed DLBCL and high-risk for CNS relapse, treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or R-CHOP-like regimens from 2001 to 2017, of whom 295 (50%) received prophylaxis. Intrathecal (IT) MTX was given to 253 (86%) and high-dose MTX (HD-MTX) to 42 (14%). After a median follow-up of 6.8 years, 36 of 585 patients relapsed in the CNS, of whom 14 had received prophylaxis. The CNS relapse risk at 1 year was lower for patients who received prophylaxis than patients who did not: 2% vs. 7.1%. However, the difference became less significant over time (5-year risk 5.6% vs. 7.5%), indicating prophylaxis tended to delay CNS relapse rather than prevent it. Furthermore, the CNS relapse risk was similar in patients who received IT and HD-MTX (5-year risk 5.6% vs. 5.2%). Collectively, our data indicate the benefit of MTX for CNS prophylaxis is transient, highlighting the need for more effective prophylactic regimens. In addition, our results failed to demonstrate a clinical advantage for the HD-MTX regimen.This work was supported in part by research funding from Fundación Alfonso Martín Escudero to SB. Data from this manuscript were presented at the 61st Annual Meeting of the American Society of Hematology, Orlando, FL, December 7th–10th, 2019

B-Type Natriuretic Peptide in Pregnant Women With Heart Disease

ObjectivesThe objectives of this study were to examine: 1) B-type natriuretic peptide (BNP) response to pregnancy in women with heart disease; and 2) the relationship between BNP levels and adverse maternal cardiac events during pregnancy.BackgroundPregnancy imposes a hemodynamic stress on the heart. BNP might be a useful biomarker to assess the ability of the heart to adapt to the hemodynamic load of pregnancy.MethodsThis was a prospective study of women with structural heart disease seen at our center. Serial clinical data and plasma BNP measurements were obtained during the first trimester, third trimester, and after delivery (>6 weeks).ResultsSeventy-eight pregnant women were studied; 66 women with heart disease (age 31 ± 5 years), and 12 healthy women (age 33 ± 5 years). During pregnancy, the median peak BNP level was higher in women with heart disease compared with control subjects (median 79, interquartile range 51 to 152 pg/ml vs. median 35, interquartile range 21 to 43 pg/ml, p < 0.001). In women with heart disease, those with subaortic ventricular dysfunction had higher BNP levels (p = 0.03). A BNP >100 pg/ml was measured in all women with events during pregnancy (n = 8). Sixteen women had increased BNP levels during pregnancy but did not have clinical events. None of the women with BNP ≤100 pg/ml had events. BNP ≤100 pg/ml had a negative predictive value of 100% for identifying events during pregnancy.ConclusionsMany pregnant women with heart disease have increased BNP levels during pregnancy. Incorporating serial BNP levels in into clinical practice can be helpful, specifically in adjudicating suspected adverse cardiac events during pregnancy

Feasibility of a lifestyle intervention in early pregnancy to prevent deterioration of glucose tolerance

<p>Abstract</p> <p>Background</p> <p>In conjunction with the growing prevalence of obesity and the older age of pregnant women gestational diabetes (GDM) is a major health problem.</p> <p>The aim of the study was to evaluate if a lifestyle intervention since early pregnancy is feasible in improving the glucose tolerance of women at a high-risk for GDM in Finland.</p> <p>Methods</p> <p>A 75-g oral glucose tolerance test (OGTT) was performed in early pregnancy (n = 102). Women at high risk for GDM (n = 54) were randomized at weeks 8-12 from Apr 2005 to May 2006 to a lifestyle intervention group (n = 27) or to a close follow-up group (n = 27). An OGTT was performed again at weeks 26-28 for the lifestyle intervention and close follow-up groups.</p> <p>Results</p> <p>The values of the OGTT during the second trimester did not differ between the lifestyle intervention and close follow-up groups. In the lifestyle intervention group three women had GDM in the second trimester and respectively one woman in the close follow up group. Insulin therapy was not required in both groups. The intervention resulted in somewhat lower weight gain 11.4 ± 6.0 kg vs. 13.9 ± 5.1 kg, p = 0.062, adjusted by the prepregnancy weight.</p> <p>Conclusions</p> <p>Early intervention with an OGTT and simple lifestyle advice is feasible. A more intensive lifestyle intervention did not offer additional benefits with respect to glucose tolerance, although it tended to ameliorate the weight gain.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01130012">NCT01130012</a></p

Herpes Simplex Encephalitis as a Complication of Whole-Brain Radiotherapy: A Case Report and Review of the Literature

A 55-year-old male recently diagnosed with stage IV lung adenocarcinoma presented with altered mental status approximately 1 week after the completion of 14 fractions of whole-brain radiotherapy (WBRT) for brain metastases. On admission, he was somnolent but oriented and without focal neurological deficits. Brain imaging revealed marked regression of his brain metastases. Laboratory values were only significant for hyponatremia with urine hyperosmolality consistent with syndrome of inappropriate antidiuretic hormone secretion. The patient developed seizures 3 days after admission, at which time cerebrospinal fluid was significant for positive herpes simplex virus (HSV)-1 PCR but with a negative cell count, and acyclovir was started for HSV encephalitis (HSE). After 3 weeks of acyclovir 10 mg/dl i.v. 3 times per day, he had significant neurological recovery and was discharged. Although HSE is a relatively rare condition, it is the most common cause of sporadic encephalitis in Western countries. Since the pathogenesis is believed to be due to the reactivation of latent HSV, it is possible that patients who are immunosuppressed are at higher risk for HSE. In addition, patients who are immunosuppressed or immunocompromised often present atypically, which may delay time to diagnosis and treatment, thus significantly worsening prognosis. This case report intends to raise awareness of this severe condition in the context of patients who have received WBRT and immunosuppressive therapy. In addition, important considerations of diagnosis and treatment of HSE in this patient population are discussed

Early data from a phase II trial investigating the combination of pembrolizumab (PEM) and entinostat (ENT) in relapsed and refractory (R/R) Hodgkin lymphoma (HL)

Abstract only e20018 Background: Histone deacetylase (HDAC) inhibitors have single agent activity in various types of lymphoma. They have been shown to restore antigen-specific immune recognition in cancer cells and to downregulate PD-1 expression in circulating T lymphocytes. In preclinical studies, the combination of HDAC inhibitors and anti-PD-1 antibodies acts synergistically against various tumor models in mice. Accordingly, we investigated the safety and efficacy of the novel combination of the HDAC inhibitor ENT and the PD-1-blocking antibody PEM in patients with R/R HL. Methods: Patients with R/R HL received ENT 5-7 mg orally once weekly and PEM 200 mg intravenously once every three weeks. The primary objective is overall response rate (ORR) and 12-month progression-free survival (PFS). Multiplexed serum cytokine analysis of 20 pro-inflammatory cytokines and chemokines was performed on sera from peripheral blood samples collected at baseline and at 21 days on treatment. Results: At data cutoff on 2/5/20, 14 patients with HL have been enrolled. Out of 13 evaluable patients, 12 responded (92% ORR), including 3 who progressed on prior anti-PD-1 therapy. With a median duration of follow-up of 176 days (21-632), 9 patients are currently receiving treatment on study, 2 discontinued due to toxicity, 1 for progression, and 2 for consolidation with transplant or radiation. After 21 days on treatment, there was a decrease in median serum levels of eotaxin (-39%, p = 0.002), eotaxin-3 (-56%, p = 0.04), MDC (-78%, p = 0.025), MIP1a (-60%, p = 0.025), and TARC (-98%, p < 0.001) and a 3-fold increase in median levels of IFNγ (p = 0.032). There was an association between extent of tumor reduction and greater decrease in the cytokines eotaxin-3 (-62%, p = 0.064), MDC (-90%, p = 0.064), and MIP1a (-85%, p = 0.064), which trended towards statistical significance. Out of 22 total patients enrolled in this study (including 8 patients with follicular lymphoma), 62% had grade ≥3 adverse events (AE), which were predominantly hematologic, including neutropenia (48%), thrombocytopenia (19%), and anemia (10%). Immune-related AEs included 3 cases of hypothyroidism, 2 cases of hepatitis and 1 case of pneumonitis. Four patients who experienced serious AEs due to pericarditis (n = 2), hemophagocytic lymphohistiocytosis, and bullous dermatitis were taken off study. Conclusions: Early results from this ongoing phase II clinical trial suggest that the combination of PEM and ENT is safe with encouraging responses in HL. Clinical trial information: NCT03179930

Use of a real-world synthetic control arm for direct comparison of lisocabtagene maraleucel and conventional therapy in relapsed/refractory large B-cell lymphoma

This study used a real-world population as a synthetic comparator for the single-arm TRANSCEND NHL 001 study (TRANSCEND; NCT02631044) to evaluate the efficacy of lisocabtagene maraleucel (liso-cel) compared with conventional (noncellular) therapies in patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Inclusion and exclusion criteria for the real-world study closely matched the enrollment criteria in TRANSCEND. The analytic comparator cohort was created by matching and balancing observed baseline characteristics of real-world patients with those in TRANSCEND using propensity score methodology. Efficacy outcomes comparing liso-cel– (n = 257) and conventional therapy–treated (n = 257) patients, respectively, significantly favored liso-cel: overall response rate (74% vs 39%; p < 0.0001), complete response rate (50% vs 24%; p < 0.0001), median overall survival (23.5 vs 6.8 months; p < 0.0001), and median progression-free survival (3.5 vs 2.2 months; p < 0.0001). These results demonstrated a statistically significant and clinically meaningful benefit of liso-cel in patients with third- or later-line R/R LBCL relative to conventional therapies. Clinical trial registration: ClinicalTrials.gov identifier: NCT02631044