Real world risk of infusion reactions and effectiveness of front-line obinutuzumab plus chlorambucil compared with other frontline treatments for chronic lymphocytic leukemia.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in North America. Previous studies have shown improved progression free survival (PFS) and response rates in unfit patients treated with obinutuzumab compared to other regimens. The aim of this study was to evaluate the obinutuzumab-chlorambucil regimen in the context of historical treatments and first-dose infusion reactions at CancerCare Manitoba (CCMB). METHODS: A retrospective chart review was conducted for patients treated with obinutuzumab from January 1, 2014 to December 31, 2017 at CCMB. A minimum data set was extracted for patients treated with other front-line therapies. Descriptive statistics were used to evaluate patient demographics, toxicity, duration and dosing of obinutuzumab treatment. Kaplan-Meier curves were used to evaluate time-to-next-treatment (TTNT), overall survival (OS) and PFS for patients treated with obinutuzumab. A multivariable logistic regression model was used to investigate associations between infusion related reactions (IRRs) and age at treatment, pre-treatment lymphocyte count, cumulative illness rating scale (CIRS) and receipt of prior chemotherapy. RESULTS: Forty seven percent of patients receiving frontline therapy received chlorambucil and obinutuzumab. Sixty-seven patients were treated with obinutuzumab and consisted of 36 males (53.7%) and 31 females (46.3%) with 29 patients (43.3%) over age 75 years. Rates of grade 3 and 4 obinutuzumab IRRs were lower (6%) compared to the CLL11 clinical trial (20%) due to local practices including slower infusion rates and using chlorambucil before starting obinutuzumab treatment. Many patients had difficulty tolerating the full dosage of chlorambucil. Only 26 patients (38.8%) had their dose of chlorambucil escalated to the full dose of 0.5 mg/kg. In addition, only 18 patients (26.9%) received all doses of obinutuzumab and all 12 doses of chlorambucil. CONCLUSIONS: In summary, first dose infusion reactions with obinutuzumab can be markedly reduced by using chlorambucil to decrease the lymphocyte count before obinutuzumab and by using a very slow initial obinutuzumab infusion rate. Modifications in chlorambucil dosing and obinutuzumab administration can improve tolerance without significant loss in efficacy.

Low-dose subcutaneous immunoglobulin is an effective treatment for autoimmune bullous skin disorders: A case report.

Intravenous immunoglobulin is a recognized treatment in recalcitrant autoimmune bullous diseases. Infusions are administered monthly over 1-5 days in the hospital setting and associated with mild to severe infusion-related systemic effects, in part due to the high doses necessary to induce and achieve remission. We present a case series of four patients with bullous diseases treated successfully with low-dose subcutaneous IgG who achieved remission with maintenance therapy. Patient-administered smaller, more frequent doses of IgG into subcutaneous tissue more closely mimics the body's own antibody production and produces a more stable serum trough level. Subcutaneous IgG is a novel treatment approach in bullous diseases which can induce a state remission.

IgA levels at diagnosis predict for infections, time to treatment, and survival in chronic lymphocytic leukemia.

To better understand the relationship between baseline immunoglobulin measurements and subsequent clinical outcomes in chronic lymphocytic leukemia (CLL), we performed a retrospective analysis on 660 patients with CLL (72%), monoclonal B-cell lymphocytosis (MBL) (13%), and small lymphocytic lymphoma (SLL) (14%), diagnosed between 2005 and 2014 at CancerCare Manitoba. Of 511 patients who had their first immunoglobulin level determined within 3 months of diagnosis, abnormal (either increased or decreased) immunoglobulin M (IgM), IgG, and IgA values were observed in 58% of patients with CLL, 27% of patients with MBL, and 20% of patients with SLL. Immunoglobulin deviances were similar for MBL and CLL Rai stage 0 and for SLL and Rai stages I and II; for CLL, IgG and IgA abnormalities occurred with increasing frequency with advancing Rai stage. In contrast, the frequency of IgM abnormalities was similar in all patient groups. IgA abnormalities significantly correlated with high ß2-microglobulin (B2M) expression, whereas abnormal IgG and IgA levels were associated with the use of IGHV1-69, 3-21, and 3-49 subtypes. Increases in IgG or IgM were commonly associated with the presence of a CLL-type M-band, whereas oligoclonal bands were frequently observed with increased IgA levels. Although abnormal levels of IgG and IgA at diagnosis were independent predictors for future immunoglobulin replacement, only abnormal IgA levels were associated with shorter time to first treatment and overall survival. These findings indicate that both reduced and elevated levels of IgG and IgA at diagnosis are important and independent prognostic markers for infection in CLL, with IgA being more relevant as a marker of disease progression and survival.

Risk factors for skin cancer and solid tumors in newly diagnosed patients with chronic lymphocytic leukemia and the impact of skin surveillance on survival.

A retrospective analysis on 587 patients with chronic lymphocytic leukemia (CLL) assessed risk factors for skin cancer and the influence of skin cancers on survival and incidence of solid tumors (STs). Patients underwent skin surveillance and were followed for a median of 6.65 years. The relative risk for skin cancer increased prior to CLL diagnosis rising 4-fold one-year post-diagnosis. Independent predictors for skin cancer were male gender (p = .0001), age ≥70 years (p = .0036) and prior chemotherapy (p = .0116). There was no increase in mortality from skin cancer and neither skin cancer nor chemotherapy increased the risk for a ST. The development of a ST was an independent predictor of survival (p < .0001) and 43% of deaths were related to STs. Thus, regular skin surveillance can prevent increased mortality from skin cancer, but not STs, in CLL. Close skin monitoring is required for elderly males who received chemotherapy.

The Evolving Context of Driver Mutations: ROS1 Rearrangement in Metastatic Non-Small Cell Lung Cancer.

A previously healthy, 30-year-old Filipino woman presented to an emergency department with complaints of shortness of breath and mild cough. She denied constitutional symptoms, such as night sweats, fevers, loss of appetite, or weight loss. Additional investigation revealed bilateral pleural and pericardial effusions with no obvious lung lesions or masses. The pericardial fluid was drained and preliminary cytology revealed atypical carcinoma cells. Her past medical history included an embryonic pregnancy and a benign breast cyst that was biopsied in the Philippines. She had immigrated to Canada two years earlier, was working full-time, and was living with her sister. She was planning on returning to the Philippines to wed and had a strong support system in Canada. She had never smoked cigarettes or consumed alcohol and had no family history of cancer. The patient was exposed to secondhand smoke as a child.
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Subcutaneous Immunoglobulin in Oncology Clinical Practice.

The administration of gammaglobulin as replacement therapy to boost immune function in patients with immunodeficiency secondary to malignancy is traditionally given in the IV formulation. A pilot program at a large Canadian cancer center led by an advanced practice nurse (APN) demonstrated that transitioning patients to home-based, self-administered subcutaneous infusions (subcutaneous immunoglobulin [SCIG]) led to savings and benefits for patients and the institution. The implementation of SCIG in oncology by an APN is a novel and innovative patient-centered approach to supportive care.

Severe Obesity in Cancer Care.

Increasing weight and body fat composition has an impact on cancer detection and staging. Obese women are less likely to engage in breast and cervical screening practices. Excessive adipose tissue makes physical assessment more difficult, and patients with a BMI greater than 35 kg/m2 may have deeper and wider pelvic structures, which make internal examinations problematic. A retrospective review of 324 primary surgical patients found that patients with a BMI greater than 40 kg/m2 are seven times less likely to undergo complete surgical staging for endometrial cancer compared with individuals with a BMI less than 40 kg/m2. In addition, healthcare provider bias against the need for screening, feelings of discomfort and embarrassment, as well as patient's fears of guilt, humiliation, and shame pose significant barriers to addressing the issue of obesity in clinical care with patients and family members. 
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Hairy Cell Leukemia and Bone Pain.

Hairy cell leukemia is a relatively rare but distinct B-cell lympho-proliferative disorder of the blood, bone marrow, and spleen that accounts for only 2% of all adult leukemia cases. The median age at presentation is 50-55 years, with a 4:1 male to female predominance. Although considered uncommon, a number of unusual clinical presentations have been noted in the literature, including the presence of peripheral lymphadenopathy, lytic bone lesions, skin involvement, organ involvement, and central nervous system involvement. Unlike the clinical management of other hematologic malignancies, no current system is used to stage hairy cell leukemia.

Virchow's Node and Carcinoma of Unknown Primary.

Virchow's node is the enlargement of the left supraclavicular lymph node and is considered by clinicians to be a strong indicator of metastatic abdominal malignancy. Virchow's node is located medially and is a deep-seeded node, making it difficult to assess in a healthy individual.

Malakoplakia After Allogeneic Hematopoietic Stem Cell Transplantation.

A 32-year-old woman named A.C. was diagnosed five years ago with stage IIIB nodular sclerosing Hodgkin lymphoma (HL). Following initial chemotherapy, she had refractory disease as evidenced by hypermetabolic activity on positron-emission tomography (PET) scan. A.C. was treated with a short course of salvage chemotherapy, stem cell collection, and autologous HSCT about 11 months after initial diagnosis. Her post-transplantation course was complicated by pneumonia and interstitial lung disease secondary to chemotherapy that rapidly improved with high-dose steroids
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Richter syndrome: an aggressive transformation.

A 71-year-old male patient named M.R. was diagnosed with chronic lymphocytic leukemia (CLL). At the time of diagnosis, M.R. had generalized lymphadenopathy and splenomegaly, which caused him to experience significant abdominal discomfort. M.R. was treated with six cycles of fludarabine, cyclophosphamide, and rituximab (FCR), which is standard first-line chemotherapy, and tolerated this fairly well. His lymphadenopathy quickly resolved and, aside from mild nausea, had no complications from treatment. 
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