Updated results from the phase 3 HELIOS study of ibrutinib, bendamustine, and rituximab in relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma.

We report follow-up results from the randomized, placebo-controlled, phase 3 HELIOS trial of ibrutinib+bendamustine and rituximab (BR) for previously treated chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) without deletion 17p. Overall, 578 patients were randomized 1:1 to either ibrutinib (420 mg daily) or placebo, in combination with 6 cycles of BR, followed by ibrutinib or placebo alone. Median follow-up was 34.8 months (range: 0.1-45.8). Investigator-assessed median progression-free survival (PFS) was not reached for ibrutinib+BR, versus 14.3 months for placebo+BR (hazard ratio [HR] [95% CI], 0.206 [0.159-0.265]; P < 0.0001); 36-month PFS rates were 68.0% versus 13.9%, respectively. The results are consistent with the primary analysis findings (HR = 0.203, as assessed by independent review committee, with 17-month median follow-up). Median overall survival was not reached in either arm; HR (95% CI) for ibrutinib+BR versus placebo: 0.652 (0.454-0.935; P = 0.019). Minimal residual disease (MRD)-negative response rates were 26.3% for ibrutinib+BR and 6.2% for placebo+BR (P < 0.0001). Incidence of treatment-emergent adverse events (including grades 3-4) were generally consistent with the initial HELIOS report. These long-term data support improved survival outcomes and deepening responses with ibrutinib+BR compared with BR in relapsed CLL/SLL.

Autologous stem cell transplantation for patients aged 60 years or older with refractory or relapsed classical Hodgkin's lymphoma: a retrospective analysis from the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC).

This report retrospectively analyzed the outcome of 91 patients aged 60 years or older with refractory/relapsed (R/R) classical Hodgkin's lymphoma (cHL) who underwent autologous stem cell transplantation (ASCT) between 1992 and 2013 and were reported to the French Society of Bone Marrow Transplantation and Cell Therapies registry. The median age at transplant was 63 years. The majority of patients exhibited disease chemosensitivity to salvage treatment (57 complete responses, 30 partial responses, 1 progressive disease and 3 unknown). The most frequent conditioning regimen consisted of BCNU, cytarabine, etoposide, melphalan (BEAM) chemotherapy (93%). With a median follow-up of 54 months, 5-year estimates of overall survival (OS) and progression free survival (PFS) for the entire group were 67 and 54%, respectively. Despite the missing data, in univariate analysis, the number of salvage chemotherapy lines (1-2 versus ⩾3) significantly influenced the OS, unlike the other prognostic factors (stage III-IV at relapse, disease status before ASCT and negative positron emission tomography (PET) scan) encountered in younger patients. In spite of its limitations, this retrospective study with a long-term follow-up suggests that ASCT is a valid treatment option for chemosensitive R/R cHL in selected elderly patients, with an acceptable rate of toxicity.

Ofatumumab in refractory chronic lymphocytic leukemia: experience through the French early access program.

BACKGROUND: The Autorisation Temporaire d'Utilisation (ATU) is an early access program available in France for drugs aimed at treating severe diseases not yet covered by a marketing authorization, for patients without any other therapeutic option and who cannot be included in a clinical trial. PATIENTS AND METHODS: This report presents the use of single-agent ofatumumab in 30 patients with advanced chronic lymphocytic leukemia (CLL) in the French ATU program. RESULTS: These very-high-risk patients had received multiple previous treatments (median = 6), and most had disease that was fludarabine-refractory or alemtuzumab-refractory (or both) or was unsuitable for alemtuzumab treatment. In the intent-to-treat analysis, the overall response rate was 47% (4 of 30, complete response; 10 of 30, partial response). Of 13 patients with 17p deletion, 6 displayed response to ofatumumab, including 2 complete responses. Treatment was well tolerated, with 17 grade 3 or 4 adverse events; 4 cases of grade 3 or 4 infusion reactions were reported, with favorable immediate outcome. Among nonhematologic complications, infections were the most frequent. CONCLUSION: The results confirm the efficacy and acceptable tolerability profile of ofatumumab as a single agent in severely ill patients with CLL. Attention should be paid to possible early infusion reactions to ofatumumab, as well as to the risk of infection.

Combination of gemcitabine and doxorubicin in rapidly progressive metastatic renal cell carcinoma and/or sarcomatoid renal cell carcinoma.

BACKGROUND/AIMS: Metastatic renal cell carcinoma (mRCC) can be rapidly progressive when tumors exhibit sarcomatoid or Fuhrman grade 4 features. Efficacy of gemcitabine (Gem) with doxorubicin (Dox) in sarcomatoid or rapidly progressive mRCC has been reported. We retrospectively evaluated Gem + Dox in a consecutive cohort of this particular patient population. PATIENTS AND METHODS: Patients had an Eastern Cooperative Oncology Group performance status of 2 or more and rapidly progressive mRCC or mRCC with sarcomatoid features. Gem (1,500 mg/m(2)) and Dox (50 mg/m(2)) were given every 2 weeks with granulocyte colony-stimulating factor. RESULTS: Twenty-nine patients were treated. Sarcomatoid features were predominant in 6 patients, while 14 tumors were Fuhrman grade 4. All patients had progressive mRCC within 4 months. No grade 4 toxicity or drug-related death was reported. One partial response (7 months), 1 mixed response, and 14 stable diseases (≥4 months for 9 patients) were observed and no response was seen in sarcomatoid tumors. The median disease-free survival was 3.7 months (≥6 months for 8 patients) and the median overall survival was 4.8 months (>12 months for 5 patients). CONCLUSION: This study showed a lower response rate than previously reported. Nevertheless, some patients had prolonged survival outcomes. This combination could be an option in sarcomatoid histology (NCCN guidelines) or rapidly progressive disease, but this population represents an unmet medical need.

PET scans for decision-making in metastatic renal cell carcinoma: a single-institution evaluation.

OBJECTIVE: Therapeutic decision-making in metastatic renal cell carcinoma (MRCC) is based on conventional radiological evaluation. Fluorodeoxyglucose positron emission tomography (FDG-PET) scans may modify this strategy. METHODS: Patients with MRCC for whom a therapeutic decision had been made underwent an FDG-PET scan in order to complete the standard radiological evaluation. RESULTS: Twenty-four patients and 26 FDG-PET scans were eligible. In 18 patients, metastatic disease was evaluable on the computed tomography (CT) scan; the FDG-PET scan was positive in 16 patients and negative in 10. In 2 patients, the FDG-PET scan was positive while they were considered disease free on radiological evaluation. In 5 patients (20.8%), the previous therapeutic decision was changed. Thirteen patients had a pathological evaluation for 19 sites. One patient out of 13 had a false-positive FDG-PET scan, while 4 sites out of 6 were false-negative. The sensitivity was 75% (95% CI: 47.6-92.7) and the predictive positive value was 92.3% (95% CI: 64-99.8). With a median follow-up of 24 months, 3 patients developed new metastatic sites. CONCLUSION: Our data suggest that, when positive, an FDG-PET scan may modify the decision made; when negative, it should not modify decision-making especially for surgery, owing to its sensitivity.

[Hemolytic-uremic syndrome complicating a long-term treatment with gemcitabine. Report of a case and review of the literature]. / Syndrome hémolytique et urémique compliquant un traitement au long cours par gemcitabine. A propos d'un cas, revue de la littérature.

INTRODUCTION: Gemcitabine is a nucleoside analog used in solid tumors since 1987. The main side effect is myelosuppression. Acute renal failure with thrombotic microangiopathy has also been reported. We report a new case and suggest to screen for this complication. EXEGESIS: A 71-year-old man with metastatic adenocarcinoma of the pancreas was treated with gemcitabine. He developed episodes of recurred haemolysis followed by haemolytic uremic syndrome. One single haemodialysis session was performed. No other known causes for haemolytic and uremic syndrome were found. Gemcitabine appears to be a new cause of thrombotic microangiopathy. It results from cumulative effects, arises preferentially when there is a renal dysfunction and diagnosis is often delayed. Treatment must be stopped. CONCLUSION: We suggest that reticulocyte count, haptoglobin level and urinalysis could help the clinician to maintain high vigilance and to have a rapid diagnosis for this rare disorder.

[Natural killer cell nasal lymphoma mimicking localized Wegener's disease]. / Lymphome nasal natural killer mimant une maladie de Wegener localisée.

INTRODUCTION: Primary non-Hodgkin's lymphoma of the nasal cavity is particular. Pathological characteristics mainly associate a prevalent NK lymphocyte phenotype, a frequent exposure to the Epstein-Barr virus and a poor sensitivity to radiotherapy compared to other lymph node localizations. EXEGESIS: The authors report the case of a 38-year-old man. The patient had previously presented a chronic maxillary sinusitis. After a diagnosis of Wegener's disease, the poor course under therapy resulted in a nasal lymphoma. Natural killer cell nasal lymphoma was confirmed with a leading biopsy at the same time as a serious clinical outcome. The patient died of septic shock with multivisceral failure. CONCLUSION: The two differential diagnoses of ulcerative lymphoma of the midface are ulcerative infectious diseases and Wegener's disease. We must not miss this severe disease, with its poor prognosis and variable, though sometimes rapid speed of evolution.

[Fatigue and radiotherapy. Literature review]. / Fatigue et radiothérapie. Revue de la littérature.

Fatigue is a common complaint for the cancer patient during and after radiotherapy, according to the published studies. Fatigue is a subjective symptom mostly underestimated by oncologists and other care givers. Etiology is complex, poorly understood in spite of obvious causes like insomnia, nausea, pain, depression, psychological distress, anemia, hypothyroidism, menopause disturbances, treatment adverse effects. Fatigue presents multifactorial and multidimensional aspects. To evaluate it, many tools can be used as single-item, unidimensional and multidimensional instruments. Practically, the open discussion with the patient throughout radiotherapy is essential to define it. Taking charge fatigue requires its acknowledgment by radiotherapist, treatment of associated symptoms with a multidisciplinary approach.

[Splenic vascular occlusion in the course of pancreatic cancer]. / Occlusions vasculaires spléniques au cours du cancer du pancréas.

INTRODUCTION: Pancreatic cancer is responsible for 6,000 deaths per year in France. During the course of the disease, venous thrombosis is common. Conversely, arterial thrombosis is rarely described. EXEGESIS: We report the case of a 59-year-old patient with pancreatic adenocarcinoma. Treatment by gemcitabine allowed rapid and persistent improvement of the body weight and a prolonged survival (18 months). Sudden complication, i.e. splenic arterial thrombosis, reversed the favorable outcome. CONCLUSION: Splenic venous thrombosis is a frequent complication occurring in the course of pancreatic cancer. It is easily diagnosed using abdominal computerized tomography. Arterial thrombosis is rarely observed. It might be due to either sporadic, unexpected, occurrence of cases related to the evolution of underlying pathological mechanisms, or to omitted treatment of vascular complications, as until the introduction of new anticancer drugs this disease was considered to be of very poor prognosis.

[Acute renal failure after polyvalent immunoglobulin therapy]. / Inuffisance rénale aiguë après cure d'immunoglobulines polyvalentes.

BACKGROUND: Acute renal failure can be induced by intravenous administration of immunoglobulins, especially in patients with a predisposition for nephrotoxicity. The onset and resolution of acute renal failure is typically rapid, but in some cases hemodialysis may be needed. CASE REPORT: We present 2 cases of acute renal failure associated with intravenous immunoglobulin therapy: a 76-year-old man with a history of non-insulin-dependent diabetes mellitus and hypertension and a 77-year-old woman using nonsteroidal antiinflammatory drugs. DISCUSSION: Intravenous immunoglobulins must be used with precaution in patients with risk factors for acute renal failure. In such patients, renal failure may be avoided by using preparations without sucrose.

[Acrodystrophic neuropathy of Bureau and Barrière]. / Acropathie ulcéromutilante de Bureau et Barrière.

INTRODUCTION: The acrodystrophic neuropathy described by Bureau and Barrière in the 1950s is a rare trophic complication of chronic, analgesic neuropathy due to alcohol abuse, which is at the origin of perforating ulcers of the foot, vasomotor disorders with dysautonomia, and leads to mutilating arthropathy of the lower limb. This neuroacropathy, also termed vagabonds' or vagrants' disease, usually occurs in subjects with a debilitated condition, chronic alcoholism, and unfavourable socioeconomic conditions. EXEGESIS: We report four cases of Bureau-Barrière disease which occurred in male subjects who were on average 55 years of age. The clinical presentation was close to that reported in the literature. Indeed, all four patients were alcoholic, nondiabetic and lived under conditions of precarious hygiene. Therapeutic management of the patients was difficult due to bad compliance with the treatment and persistence of alcohol abuse. Immobilization of the foot is considered to be the primary treatment. Local care including baths and bandages with hydrocolloids must be continued during several months, and associated with antibiotic therapy, administered by infusion when necessary. The outcome is often chronic, with poor prognosis. Given the limited therapeutic possibilities, acrodystrophic neuropathy is an invalidating disease with high morbidity. CONCLUSION: Bureau-Barrière disease is a rare, serious invalidating disease. The clinical symptomatology is usually based on the diagnostic triad: analgesia of the foot, perforating ulcers of the foot, and deforming and mutilating arthropathy of the lower limb. Treatment is often hampered due to poor compliance with local care and persistence of alcohol abuse.