Delayed but Complete Response following Oral Temozolomide Treatment in Melanoma Leptomeningeal Carcinomatosis

Isolated leptomeningeal recurrence of melanoma is rare, occurring in 2% of patients with central nervous system involvement secondary to melanoma. The optimal treatment of leptomeningeal carcinomatosis (LMC) in melanoma has not yet been determined and remains a major challenge. We report a melanoma patient who presented with isolated LMC in the form of a new-onset weakness of the lower limbs, paresthesia of the left hand and foot, lumbago and headache. A lumbar puncture and spinal MRI confirmed LMC. The patient was treated with temozolomide 75 mg/m2/day on a 4 weeks on/2 weeks off schedule. After an initial transient clinical deterioration, the patient showed a complete radiological response as well as a dramatic improvement in quality of life. The encouraging clinical response reported here suggests that dose-intensified temozolomide might have significant activity in the treatment of leptomeningeal dissemination of melanoma and may be a valid treatment option for patients who have not been previously exposed to this agent. Moreover, this treatment regimen is extremely well tolerated and obviates the need for repeated intrathecal administrations of chemotherapeutic agents, which are often not well tolerated by patients who have significant co-morbidities due to their disease. As illustrated in this case, response to temozolomide may occur in a delayed manner, highlighting the importance of following temozolomide treatment long enough before determining that it is inefficient in a given patient

Gastrointestinal relapse of multiple myeloma and sustained response to lenalidomide: a case report

<p>Abstract</p> <p>Introduction</p> <p>Gastrointestinal relapse in patients with multiple myeloma is very rare and, when reported, always associated with a poor prognosis.</p> <p>Case presentation</p> <p>We describe the case of a 71-year-old Caucasian man who presented with life-threatening hematemesis and melena due to a digestive relapse of his multiple myeloma. Despite the active hemorrhage, we initiated a third-line treatment with lenalidomide. The response was spectacular and long-lasting.</p> <p>Conclusions</p> <p>Clinicians must consider digestive tract involvement in myeloma patients presenting with a gastrointestinal hemorrhage. Furthermore, myeloma patients do benefit from novel oral drugs, even when they are critically ill.</p

Anticorps et tumeurs solides

Grâce aux progrès biotechnologiques récents, les anticorps monoclonaux constituent une nouvelle classe de médicaments pour le traitement des tumeurs solides. Afin d’illustrer l’intérêt de cette classe thérapeutique et son évolution, nous présentons deux anticorps utilisés en pratique quotidienne (le trastuzumab et le cétuximab), ainsi que deux cibles prometteuses pour lesquelles des anticorps devraient être prochainement disponibles (IGF-1R et c-MET). Le trastuzumab et le cétuximab ont bouleversé les stratégies thérapeutiques dans les cancers du sein, les cancers du côlon et ceux de la sphère ORL, mais leur efficacité est cependant limitée à une fraction de patients et est le plus souvent transitoire. Les défis actuels sont donc nombreux : mieux comprendre le mode d’action de ces molécules, élucider les mécanismes de résistance, exploiter la synergie entre anticorps et chimiothérapie, sélectionner les patients pour lesquels un bénéfice peut être espéré. Résoudre ces questions devrait permettre de proposer dans le futur des traitements individualisés sur la base des caractéristiques des tumeurs et des patients

Relapses of Immune Thrombocytopenia after the Second and Booster Doses of BNT162b2 Vaccine

We present here a 65-year-old male patient known for immune thrombocytopenic purpura (ITP) and fluctuating platelet count who experienced a severe exacerbation of thrombocytopenia following BNT162b2 COVID-19 vaccination. One month after the second dose, he presented petechiae and asthenia with isolated thrombocytopenia (platelet count: 3 × 109/L). He recovered after a 4-day course of intravenous corticosteroid treatment and intravenous immunoglobulin therapy. Eight months later, his platelet count was within the normal range, and he received a booster dose of vaccine after premedication with prednisone. Eight days later, his platelet count dropped to 29 × 109/L, but he remained asymptomatic. He received a rescue treatment with prednisone followed by rituximab over 4 weeks, allowing progressive improvement. Our case suggests a strong association between COVID-19 vaccination and the exacerbation of ITP

Complex influence of gonadotropins and sex steroid hormones on QT interval duration

International audienceQT interval duration is longer in women than in men. Sex steroid hormones have inconsistently been suggested to explain this difference. Implication of gonadotropins has never been studied.Objective:We here report the combined influence of sex steroid hormones and gonadotropins on QT interval duration in healthy subjects and patients with congenital adrenal hyperplasia (CAH) as a model of testosterone and progesterone overexpression.Design:Patients. Eighty four CAH patients (58 women) and 84 healthy subjects matched-paired for sex and age were prospectively included. Circulating concentrations of 17-OH-progesterone, progesterone, testosterone, estradiol, FSH and LH, were measured concomitantly to recording of a digitized electrocardiogram.Results:QTcFridericia(QTcF) was shorter in women with CAH than in control women (404±2 msec vs. 413±2.1 msec, p≤0.001). 17-OH-progesterone, progesterone, progesterone/estradiol ratio and total testosterone were higher in women with CAH than in women controls (p<0.05) whereas FSH was lower (p≤0.05). According to multivariable analysis in all women, progesterone/estradiol ratio (β=-0.33) and FSH levels (β=0.34) were related to QTcF (r=0.5, p<0.0001) with no influence of CAH or healthy status. QTcF was not different between CAH (404.7±3.7 msec) or healthy men (396±2.8 msec). For men, QTcF (r=0.48, p<0.01) was negatively related to free testosterone (β=-0.29) and positively to FSH levels (β=0.34).Conclusion:Cardiac repolarization is influenced by complex interactions between sex steroid hormones and gonadotropins depending on gender. Our results indicate that progesterone/estradiol ratio, in women, testosterone, in men, and FSH, in both genders, are major determinants of ventricular repolarization with opposite effects on QTc interval

A prospective study of the factors shaping antibody responses to the AS03-adjuvanted influenza A/H1N1 vaccine in cancer outpatients.

PURPOSE: To identify the determinants of antibody responses to adjuvanted influenza A/H1N1/09 vaccines in a cohort of cancer outpatients. PATIENTS AND METHODS: Patients with cancer and controls were enrolled in a prospective single-center field study. Two doses of AS03-adjuvanted pandemic influenza vaccine were administered to patients and one dose was administered to controls. Antibody responses were measured using hemagglutination inhibition and confirmed by microneutralization. Geometric mean titers (GMTs) and seroprotection rates (defined as GMTs ≥40) were compared. RESULTS: Immunizations were safe and well tolerated in 197 cancer patients (lymphoma, 57; glioma, 26; lung or head and neck, 37; gastrointestinal, 41; breast, 36) and 138 controls. Similar seroprotection rates (82.3% versus 87%) and GMTs (336.9 versus 329.9) were achieved after two doses of adjuvanted vaccine in cancer patients and one dose in controls. Univariate analyses identified older age, prior immunization against seasonal influenza, lymphoma, CD4 count, active chemotherapy, and rituximab and steroid treatments as being associated with weaker antibody responses. However, only age and chemotherapy plus rituximab remained independent determinants of vaccine responses in multivariate analyses. CONCLUSIONS: Two doses of AS03-adjuvanted influenza vaccine elicited potent antibody responses in most cancer patients despite ongoing chemotherapy, with the exception of rituximab-induced B-cell depletion. Oncology patients treated in an outpatient setting benefit from preventive vaccination against influenza with adjuvanted vaccines