On November 30, 2016 X4 Pharmaceuticals, a clinical stage biotechnology company developing novel CXCR4 inhibitor drugs to improve immune cell trafficking and increase the ability for T-cells to track and destroy cancer, reported the presentation of preclinical data for X4P-001, the Company’s lead drug candidate, at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Molecular Targets and Cancer Therapeutics Symposium, held November 29 – December 2 in Munich, Germany (Press release, X4 Pharmaceuticals, NOV 30, 2016, View Source [SID1234516899]). The findings in preclinical models of renal cell carcinoma (RCC) elucidate the molecular mechanism that directs the trafficking of key immune cells in the tumor microenvironment that result in synergistic anti-tumor effect of X4P-001 and axitinib, a tyrosine kinase inhibitor approved for use as a targeted therapy for RCC. The data also showed that X4P-001 blocks the critical escape mechanism that leads to resistance to treatment with axitinib, a vascular endothelial growth factor receptor (VEGF-R) antagonist cancer therapy.

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"While treatment with VEGF-R antagonists is first line therapy, it can be hindered by acquired resistance," said James W. Mier, M.D., Associate Professor of Medicine at the Beth Israel Deaconess Medical Center and senior author of the poster presentation. "These data show clear evidence that by inhibiting CXCR4, X4P-001 blocks a critical mechanism of this resistance, resulting in a synergistic anti-tumor effect which may ultimately lead to improved patient outcomes."

The poster, entitled "MDSC trafficking and function in RCC by CXCR4 in the presence of a VEGF-R antagonist is dependent on HIF-2a expression," shows that CXCR4 inhibition with X4P-001 blocks the primary pathway that leads to resistance to VEGF-R cancer therapies in renal cell carcinoma. Acquired resistance of tumors to VEGF-R antagonists is dependent on HIF-2a, CXCR4/CXCL12, and the infiltration of myeloid derived suppressor cells (MDSCs), into the tumor. CXCR4 inhibition with X4P-001 blocks communication between the tumor and MDSCs, suppresses HIF-2a expression, reduces MDSC tumor infiltration, and improves anti-tumor effect.

"These data demonstrate the potential of X4P-001 in combination with approved therapies as a potential new treatment approach to achieve impactful clinical responses for patients with advanced ccRCC, a cancer with serious unmet needs," said Paula Ragan, PhD, Founder, President and CEO of X4. "The data provide additional compelling rationale for our ongoing Phase 1/2 clinical study evaluating the combination of X4P-001 and axitinib in patients with advanced ccRCC."

About X4P-001 in Cancer
X4P-001 is an oral, small molecule inhibitor of CXCR4, or C-X-C receptor type 4, the receptor for the chemokine CXCL12 (also known as stromal derived factor-1, or SDF-1). Recent studies demonstrate that CXCR4/CXCL12 is a primary receptor-ligand pair that cancer cells and surrounding stromal cells express and use to block normal immune function and promote angiogenesis through the trafficking of T-effector and T-regulatory cells, as well as myeloid derived suppressor cells (MDSCs), in the tumor microenvironment.1, 2 Pre-clinical studies have demonstrated X4P-001 activity alone and in combination with approved cancer therapies resulted in an increased tumor-specific immune response and significant inhibition of tumor growth. X4P-001 has been tested in over 70 subjects in four clinical trials in healthy volunteers and HIV-infected patients to date and was shown to be well tolerated.

About Renal Cell Carcinoma
Kidney cancer is among the ten most common cancers in both men and women with more than 60,000 new diagnoses each year in the United States.3 Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer, and advanced ccRCC accounts for approximately 20% of the patient population. Therapies for advanced ccRCC include immunotherapies, mammalian target of rapamycin (mTOR) kinase inhibitors, and angiogenesis inhibitors, such as vascular endothelial growth factor (VEGF) inhibitors.4 There continue to be unmet medical needs with advanced ccRCC because durable responses remain a serious clinical challenge for patients with advanced disease.

On November 30, 2016 NanoString Technologies, Inc. (NASDAQ:NSTG), a provider of life science tools for translational research and molecular diagnostic products, reported the highlights of numerous advances in precision oncology and hematology using the nCounter platform that will be presented at the Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) (Press release, NanoString Technologies, NOV 30, 2016, View Source [SID1234516871]).

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"We’re excited by the volume and impact of the important translational research that our customers and collaborators are presenting at the meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper)," said Brad Gray, president and chief executive officer of NanoString Technologies. "This research includes significant advances in subtyping lymphomas and optimizing regimens to achieve better clinical outcomes."

The ASH (Free ASH Whitepaper) Annual Meeting, being held December 3-6, in San Diego, will include at least seven oral presentations and nine posters that demonstrate the unique capabilities and robust performance of the nCounter platform. In particular, several abstracts provide additional insights on the development and performance of NanoString’s assay in development for subtyping lymphoma.

In lymphoma, NanoString and its collaborators are presenting results generated using the nCounter-based Lymphoma Subtyping Test showing its analytical robustness and clinical relevance, including:

Analytical validation of the investigational nCounter-based Lymphoma Subtyping Test for cell-of-origin (COO) identification in Formalin-Fixed Paraffin-Embedded (FFPE) Diffuse Large B-Cell Lymphoma (DLBCL) Specimens. The data show that this assay provides a highly precise, sensitive and rapid method for measuring COO on FFPE DLBCL tumor specimens, including both excisional and core needle biopsies. This assay is currently being used to select patients for a phase 3 clinical trial to evaluate lenalidomide plus R-CHOP versus placebo plus R-CHOP in patients who have newly diagnosed, previously untreated ABC-type DLBCL (Abstract #2933).

Data on outcomes by COO as determined via the investigational NanoString Lymphoma Subtyping Test on patients enrolled in a phase 2 study of lenalidomide combined with R-CHOP (R2CHOP) and an independent comparison cohort of patients treated with R-CHOP alone. The results show that R2CHOP demonstrates promising efficacy in ABC-type DLBCL as defined by the NanoString assay, where the addition of lenalidomide to R-CHOP appears to mitigate the negative prognostic impact of the ABC subtype in newly diagnosed DLBCL (Abstract #3035).

Results from an open-Label, randomized phase 3 study (GOYA) comparing the efficacy and safety of obinutuzumab plus CHOP (G-CHOP) with R-CHOP in patients with previously untreated DLBCL. A pre-specified secondary analysis of cell-of-origin by the investigational NanoString Lymphoma Subtyping Test showed a trend toward benefit from Gazyva in GCB-type DLBCL. (Abstract #470).

Data on the first analysis of an international double-blind randomized phase 3 Study (REMARC) of lenalidomide maintenance in elderly patients with DLBCL treated with R-CHOP in first line, which include cell-of-origin analysis assessed by the NanoString Lymphoma Subtyping Test (Abstract #471).
The 2016 ASH (Free ASH Whitepaper) abstracts describe research and clinical applications that underscore the diverse capabilities of the nCounter platform, which NanoString will showcase at booth #3651.

Abstract # Title Hyperlink
2933 Analytical Validation of the nCounter-based Lymphoma Subtyping Test (LST) for Cell-of-Origin (COO) Identification in Formalin-Fixed Paraffin-Embedded (FFPE) Diffuse Large B-Cell Lymphoma (DLBCL) Specimens View Source
3035 Lenalidomide Combined with R-CHOP (R2CHOP) Overcomes Negative Prognostic Impact of ABC Molecular Subtype in Newly Diagnosed Diffuse Large B-Cell Lymphoma View Source
470 Obinutuzumab or Rituximab Plus CHOP in Patients with Previously Untreated Diffuse Large B-Cell Lymphoma: Final Results from an Open-Label, Randomized Phase 3 Study (GOYA) View Source
471 First Analysis of an International Double-Blind Randomized Phase III Study of Lenalidomide Maintenance in Elderly Patients with DLBCL Treated with R-CHOP in First Line, the Remarc Study from Lysa View Source
474 Lenalidomide Maintenance Significantly Improves Survival Figures in Patients with Relapsed Diffuse Large B-Cell Lymphoma (rDLBCL) Who Are Not Eligible for Autologous Stem Cell Transplantation (ASCT): Final Results of a Multicentre Phase II Trial View Source
152 Integrating Genomic Alterations in Diffuse Large B-Cell Lymphoma Identifies New Relevant Pathways and Potential Therapeutic Targets View Source
2935 Whole-Exome Analysis Reveals Novel Somatic Genomic Alterations Associated with Cell of Origin in Diffuse Large B-Cell Lymphoma View Source
1107 Pembrolizumab in Relapsed/Refractory Classical Hodgkin Lymphoma: Primary End Point Analysis of the Phase 2 Keynote-087 Study View Source
619 Phase 1b Study of Pembrolizumab in Patients with Relapsed/Refractory Primary Mediastinal Large B-Cell Lymphoma: Results from the Ongoing Keynote-013 Trial View Source
918 A Novel Anti-Lymphoma Immune Evasion Mediated By the Interaction Between PD-1 Enriched NK-Cells and CD163+PD-L1+PD-L2+ Tumor Associated Macrophages, That Is More Prominent in Hodgkin Lymphoma Than Diffuse Large B-Cell Lymphoma View Source
4576 Differential Expression of Immunity Related Genes and Early Prediction of Severe Graft Versus Host Disease after Allogeneic Hematopoietic Cell Transplantation View Source
1954 Transcriptional Characterization of Myelofibrotic Bone Marrow Microenvironment Reveals Distinct Tumor Microenvironment in JAK2+ and Calr+ PMF Marrows View Source
1664 Microvesicles microRNAs Reflect and Affect Progression of Acute Myeloid Leukemia and Could Serve As a Biomarker of Disease Dynamics View Source
3285 Integrative Network Analysis of Newly Diagnosed Multiple Myeloma Identifies a Novel RNA-Seq Based High Risk gene Signature View Source

On November 30, 2016 Heat Biologics, Inc. (Nasdaq:HTBX), a leader in the development of gp96-based immunotherapies that are designed to activate a patient’s immune system to fight cancer, reported that it presented topline data from its 94-patient Phase II trial evaluating HS-410 (vesigenurtacel-L) in combination with standard of care, Bacillus Calmette-Guérin (BCG), or as a monotherapy, for the treatment of non-muscle invasive bladder cancer, at the Society of Urologic Oncology Annual Meeting in San Antonio, TX (Press release, Heat Biologics, NOV 30, 2016, View Source [SID1234516865]).

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In the poster, "Top-Line Results from Vesigenurtacel-L (HS-410) in Combination with BCG from a Randomized, Blinded Phase 2 Trial in Patients with Non-Muscle Invasive Bladder Cancer (NMIBC)," researchers reported that there were encouraging signs of anti-tumor activity as HS-410 generated a robust antigen-specific immune response to multiple tumor-associated peptides in treated patients, while there were no immune responses of this type in the placebo. However, these responses did not translate into clinical outcomes, and there was no statistically significant difference in the primary endpoint (proportion of recurrence-free survival at one year) between the vaccine and placebo arms of the trial. To better assess the durability of the positive immunological responses, and in keeping with clinical trial guidance recently issued by International Bladder Cancer Group ("IBCG")1 recommending a 2-year study duration for NMIBC trials, Heat will continue to monitor all patients enrolled in the study for an additional 12 months. At that time, Heat will make a final determination whether to progress its bladder cancer program into a Phase 3 trial.

"The ability of HS-410 to prime T-cells suggests a strong signal that the vaccine is having an impact, as well as an opportunity to improve responses, in this challenging disease," said study principal investigator, Gary Steinberg, M.D., The Bruce and Beth White Family Professor of Surgery and Director of Urologic Oncology at the University of Chicago. "Historically, NMIBC has been very difficult to treat, with BCG being the only approved therapy in the past 40 years. We were surprised to see that all arms of this trial performed much better than historical control, which is a testament to improvements in standard of care, and validates our choice to run a controlled clinical trial. We look forward to continuing to monitor patients in this trial, per IBCG recommendations. and would like to thank the many patients and their families for the commitment to this trial and advancement of the treatment of bladder cancer."

"We were pleased to see a robust antigen-specific immune response, reinforcing our earlier clinical data," Jeff Wolf, CEO of Heat Biologics, commented. "Even though we did not achieve our desired clinical outcomes, we are encouraged by the results and believe this, and other combination therapies, have the potential to improve long-term outcomes. In particular, Heat’s ComPACT technology, combining a therapeutic vaccine with an immune co-stimulator in a single product, was designed to substantially improve immune response durability. We are actively pursuing new programs to complement our existing platforms, which we expect to announce in early 2017. Moreover, we look forward to examining the additional top-line data that will be reported next week for our combination trial of HS-110 in with Bristol-Myers Squibb’s Opdivo (nivolumab) in lung cancer."

"HS-410 stimulated antigen-specific immune responses to multiple tumor-associated peptides," commented Taylor Schreiber, M.D., Ph.D., Chief Scientific Officer. "The kinetics of these responses indicate efficient priming of CD8+ T cells, consistent with results seen in other Heat Biologics clinical trials. Remaining analyses are in progress to inform future development of other agents and/or combinations aimed at improving immune response durability. Further understanding of the secondary and exploratory endpoints will advise future development steps."

"We conducted a cost-efficient trial and will continue to gather important data with minimal ongoing costs," Mr. Wolf added. "We have maintained a solid balance sheet and intend to continue to be very prudent in managing our expenses as we generate additional clinical data and progress our programs and platforms."

Additionally, Heat will be presenting topline data on its non-small cell lung cancer study of HS-110 in combination with Bristol-Myers Squibb’s Opdivo (nivolumab) at the International Association for the Study of Lung Cancer Annual Meeting in Vienna, Austria, on December 6th. The presentation, "Viagenpumatucel-L Bolsters Response to Nivolumab Therapy in Advanced Lung Adenocarcinoma: Preliminary Data from the DURGA Trial" will occur on December 6, 2016, 8:56 AM EST (14:56 CET). Following this data release, Heat plans to hold an investor call on December 8th to discuss its overall clinical strategy moving forward.

1 Definitions, End Points, and Clinical Trial Designs for Non–Muscle-Invasive Bladder Cancer: Recommendations from the International Bladder Cancer Group, Journal of Clinical Oncology, 34(16):1935-44, June, 2016.

On November 30, 2016 Galena Biopharma, Inc. (NASDAQ:GALE), a biopharmaceutical company committed to the development and commercialization of hematology and oncology therapeutics that address unmet medical needs, reported that two posters will be presented at the upcoming San Antonio Breast Cancer Symposium taking place December 6-10, 2016 in San Antonio, TX (Press release, Galena Biopharma, NOV 30, 2016, View Source [SID1234516851]).

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A poster will be presented on the trial design for the planned, Phase 2 investigator-sponsored clinical trial with NeuVax (nelipepimut-S) in patients with Ductal Carcinoma in Situ (DCIS). The trial is being run in collaboration with the National Cancer Institute (NCI) and The University of Texas MD Anderson Cancer Center Phase I and II Chemoprevention Consortium. The trial was suspended in July 2016, but is now open for enrollment and is expected to initiate by the end of the year. Details of the poster presentation are as follows:

Title: VADIS trial: Phase 2 trial of the nelipepimut-S peptide vaccine in women with DCIS of the breast
Session Title: Ongoing Clinical Trials: Ongoing Trials — Immunotherapy
Date: Friday, December 9, 2016
Time: 5:00 p.m. to 7:00 p.m. local time
Location: Hall 1
Poster #: 1646
Abstract #: OT3-01-04 – the abstract can be found on the conference website here
A poster will be presented on the breast cancer patients in the Company’s GALE-301 (E39) and GALE-302 (E39’) Phase 1b clinical trial targeting Folate Binding Protein. Details of the poster presentation are as follows:

Title: Determining the optimal vaccination strategy using a combination of the folate binding protein (FBP) peptide vaccine (E39+GM-CSF) and an attenuated version (E39′) to maximize the immunologic response in breast cancer patients
Session Title: Poster Session 6: Treatment: Immunotherapy (Clinical)
Date: Saturday, December 10, 2016
Time: 7:30 a.m. to 9:00 a.m. local time
Location: Hall 1
Abstract #: P6-10-04 – the abstract can be found on the conference website here
About NeuVax (nelipepimut-S)

NeuVax (nelipepimut-S) is a first-in-class, HER2-directed cancer immunotherapy under evaluation to prevent breast cancer recurrence after standard of care treatment in the adjuvant setting. It is the immunodominant peptide derived from the extracellular domain of the HER2 protein, a well-established target for therapeutic intervention in breast carcinoma. The nelipepimut-S sequence stimulates specific CD8+ cytotoxic T lymphocytes (CTLs) following binding to specific HLA molecules on antigen presenting cells (APC). These activated specific CTLs recognize, neutralize and destroy, through cell lysis, HER2 expressing cancer cells, including occult cancer cells and micrometastatic foci. The nelipepimut-S immune response can also generate CTLs to other immunogenic peptides through inter- and intra-antigenic epitope spreading. In clinical studies, NeuVax is combined with recombinant granulocyte macrophage-colony stimulating factor (GM-CSF).

NeuVax is currently in two breast cancer studies in combination with trastuzumab (Herceptin; Genentech/Roche): a Phase 2b trial in node positive and triple negative HER2 IHC 1+/2+ (clinicaltrials.gov identifier: NCT01570036); and, a Phase 2 trial in high risk, node positive or negative HER2 IHC 3+ patients (clinicaltrials.gov identifier: NCT02297698). Phase 2 clinical trials with NeuVax are also planned in patients with ductal carcinoma in situ (DCIS), and in patients with gastric cancer.

About Ductal Carcinoma in Situ

Ductal Carcinoma in Situ (DUK-tul KAR-sih-NOH-muh in SY-too), or DCIS, is defined by the NCI as a noninvasive condition in which abnormal cells are found in the lining of a breast duct, and is the most common type of breast cancer. The abnormal cells have not spread outside the duct to other tissues in the breast. In some cases, DCIS may become invasive cancer and spread to other tissues; currently there is no way to know which lesions could become invasive. Current treatment options for DCIS include breast-conserving surgery and radiation therapy with or without tamoxifen, breast-conserving surgery without radiation therapy, or total mastectomy with or without tamoxifen. According to the American Cancer Society, in 2015 there were over 60,000 diagnoses of ductal carcinoma in situ.

About GALE-301 and GALE-302

GALE-301 and GALE-302 are cancer immunotherapies that consist of a peptide derived from Folate Binding Protein (FBP) combined with the immune adjuvant, granulocyte macrophage-colony stimulating factor (GM-CSF) for the prevention of cancer recurrence in the adjuvant setting. GALE-301 is the E39 peptide, while GALE-302 is an attenuated version of this peptide, known as E39’. FBP is a well-validated therapeutic target that is highly over-expressed in ovarian, endometrial and breast cancers, and is the source of immunogenic peptides that can stimulate cytotoxic T lymphocytes (CTLs) to recognize and destroy FBP-expressing cancer cells. Two trials are ongoing with FBP peptides: the GALE-301 Phase 2a portion of the Phase 1/2a clinical trial is ongoing in ovarian and endometrial adenocarcinomas (ClinicalTrials.gov Identifier: NCT01580696); the GALE-301 plus GALE-302 Phase 1b clinical trial is ongoing in breast and ovarian cancers (ClinicalTrials.gov Identifier: NCT02019524).

About Breast Cancer1

New cases of breast cancer occur at an annual rate of 125 per 100,000 women in the U.S., with an estimated 246,660 new cases and 40,450 deaths in 2016. Approximately 89.7% of breast cancer patients are expected to survive five years after diagnosis. Approximately 12.4% of women will be diagnosed with breast cancer at some point during their lifetime (2011 – 2013 data). The prevalence data from 2013 showed an estimated 3,053,450 women living with breast cancer in the United States.

1National Cancer Institute Surveillance, Epidemiology, and End Results Program

On November 30, 2016 Teva Pharmaceutical Industries Ltd., (NYSE and TASE:TEVA) reported that data on GRANIX (tbo-filgrastim) Injection, TREANDA (bendamustine HCl) Injection and TRISENOX (arsenic trioxide) Injection will be presented during poster sessions at the 2016 ASH (Free ASH Whitepaper) Annual Meeting to be held at the San Diego Convention Center in San Diego, CA on December 3-6, 2016 (Press release, Teva, NOV 30, 2016, View Source;p=RssLanding&cat=news&id=2226456 [SID1234516848]). Additional bendamustine abstracts were also accepted for publication in an online issue of Blood to be issued during the annual meeting.

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"We look forward to sharing real world data and outcomes research from our Oncology portfolio that provide deeper insights into our products," said Richard Nieman, M.D., Senior Vice President, Global Medical Affairs, Teva Pharmaceuticals. "The presentations at this year’s ASH (Free ASH Whitepaper) Meeting further highlight Teva’s commitment to providing innovative medicines that positively impact our healthcare system, treatment and management of disease, and the lives of people, particularly those affected by cancer."

Teva-sponsored data to be presented include:
GRANIX (tbo-filgrastim) Injection
P2504: Real-World Safety Experience for Short-Acting Recombinant Human Granulocyte Colony-Stimulating Factor.

This abstract will be presented during Granulocytes, Monocytes, and Macrophages on Sunday, December 4, 2016, 6:00 p.m. to 8:00 p.m. in Hall GH
P2407: Budget Impact Analysis of Treating Chemotherapy Patients with Health Care Provider-Administered Tbo-Filgrastim, Filgrastim-Sndz, and Filgrastim in the United States.
This abstract will be presented during Outcomes Research—Malignant Conditions on Saturday, December 3, 2016, 5:30 p.m. to 7:30 p.m. in Hall GH
P4786: Budget Impact Analysis of Treating Chemotherapy Patients with Patient-Administered Tbo-Filgrastim, Filgrastim-Sndz, and Filgrastim in the United States.
This abstract will be presented during Outcomes Research—Malignant Conditions on Monday, December 5, 2016, 6:00 p.m. to 8:00 p.m. in Hall GH
TREANDA (bendamustine HCl) Injection
P2406: Differences in Healthcare Utilization in Chronic Lymphocytic Leukemia (CLL) Patient Treated With Bendamustine plus Rituximab (BR) Versus Fludarabine, Cyclophosphamide, and Rituximab (FCR).
This abstract will be presented during Outcomes Research—Malignant Conditions on Saturday, December 3, 2016, 5:30 p.m. to 7:30 p.m. in Hall GH
TRISENOX (arsenic trioxide) Injection
P4034: Long-Term Safety Experience with Arsenic Trioxide in Patients with Acute Promyelocytic Leukemia.
This abstract will be presented during Acute Myeloid Leukemia: Commercially Available Therapy, excluding Transplantation on Monday, December 5, 2016, 6:00 p.m. to 8:00 p.m. in Hall GH

GRANIX (tbo-filgrastim) Injection
Indication
GRANIX is a leukocyte growth factor indicated to reduce the duration of severe neutropenia in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia.
Important Safety Information for GRANIX (tbo-filgrastim) Injection
Splenic rupture: Splenic rupture, including fatal cases, can occur following the administration of human granulocyte colony-stimulating factors (hG-CSFs). Discontinue GRANIX and evaluate for an enlarged spleen or splenic rupture in patients who report upper abdominal or shoulder pain after receiving GRANIX.
Acute respiratory distress syndrome (ARDS): ARDS can occur in patients receiving hG-CSFs. Evaluate patients who develop fever and lung infiltrates or respiratory distress after receiving GRANIX, for ARDS. Discontinue GRANIX in patients with ARDS.
Allergic reactions: Serious allergic reactions, including anaphylaxis, can occur in patients receiving hG-CSFs. Reactions can occur on initial exposure. Permanently discontinue GRANIX in patients with serious allergic reactions. Do not administer GRANIX to patients with a history of serious allergic reactions to filgrastim or pegfilgrastim.
Use in patients with sickle cell disease: Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disease receiving hG-CSFs. Consider the potential risks and benefits prior to the administration of GRANIX in patients with sickle cell disease. Discontinue GRANIX in patients undergoing a sickle cell crisis.
Capillary leak syndrome (CLS): CLS can occur in patients receiving hG-CSFs and is characterized by hypotension, hypoalbuminemia, edema and hemoconcentration. Episodes vary in frequency, severity and may be life-threatening if treatment is delayed. Patients who develop symptoms of CLS should be closely monitored and receive standard symptomatic treatment, which may include a need for intensive care.
Potential for tumor growth stimulatory effects on malignant cells: The granulocyte colony-stimulating factor (G-CSF) receptor, through which GRANIX acts, has been found on tumor cell lines. The possibility that GRANIX acts as a growth factor for any tumor type, including myeloid malignancies and myelodysplasia, diseases for which GRANIX is not approved, cannot be excluded.
Most common treatment-emergent adverse reaction: The most common treatment-emergent adverse reaction that occurred in patients treated with GRANIX at the recommended dose with an incidence of at least 1% or greater and two times more frequent than in the placebo group was bone pain.
Please see Full Prescribing Information for GRANIX (tbo-filgrastim) Injection
TREANDA (bendamustine HCl) Injection
Indications
TREANDA is indicated for the treatment of patients with chronic lymphocytic leukemia (CLL). Efficacy relative to first-line therapies other than chlorambucil has not been established.
TREANDA is indicated for the treatment of patients with indolent B-cell non-Hodgkin lymphoma (NHL) that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen.
Important Safety Information for TREANDA (bendamustine HCl) Injection
Contraindication: TREANDA is contraindicated in patients with a known hypersensitivity (e.g., anaphylactic and anaphylactoid reactions) to bendamustine.
Myelosuppression: TREANDA caused severe myelosuppression (Grade 3-4) in 98% of patients in the two NHL studies. Three patients (2%) died from myelosuppression-related adverse reactions. If myelosuppression occurs, monitor leukocytes, platelets, hemoglobin (Hgb), and neutrophils frequently. Myelosuppression may require dose delays and/or subsequent dose reductions if recovery to the recommended values has not occurred by the first day of the next scheduled cycle.
Infections: Infection, including pneumonia, sepsis, septic shock, hepatitis and death have occurred. Patients with myelosuppression following treatment with TREANDA are more susceptible to infections. Patients treated with TREANDA are at risk for reactivation of infections including (but not limited to) hepatitis B, cytomegalovirus, Mycobacterium tuberculosis, and herpes zoster. Patients should undergo appropriate measures (including clinical and laboratory monitoring, prophylaxis, and treatment) for infection and infection reactivation prior to administration.
Anaphylaxis and Infusion Reactions: Infusion reactions to TREANDA have occurred commonly in clinical trials. Symptoms include fever, chills, pruritus, and rash. In rare instances severe anaphylactic and anaphylactoid reactions have occurred, particularly in the second and subsequent cycles of therapy. Monitor clinically and discontinue drug for severe (Grade 3-4) reactions. Ask patients about symptoms suggestive of infusion reactions after their first cycle of therapy. Consider measures to prevent severe reactions, including antihistamines, antipyretics, and corticosteroids in subsequent cycles in patients who have experienced Grade 1 or 2 infusion reactions.
Tumor Lysis Syndrome: Tumor lysis syndrome associated with TREANDA treatment has occurred. The onset tends to be within the first treatment cycle of TREANDA and, without intervention, may lead to acute renal failure and death. Preventive measures include vigorous hydration and close monitoring of blood chemistry, particularly potassium and uric acid levels. There may be an increased risk of severe skin toxicity when TREANDA and allopurinol are administered concomitantly.
Skin Reactions: Fatal and serious skin reactions have been reported with TREANDA treatment and include, toxic skin reactions, [Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS)], bullous exanthema and rash. Events occurred when TREANDA was given as a single agent and in combination with other anticancer agents or allopurinol. Where skin reactions occur, they may be progressive and increase in severity with further treatment. Monitor patients with skin reactions closely. If skin reactions are severe or progressive, withhold or discontinue TREANDA.
Hepatotoxicity: Fatal and serious cases of liver injury have been reported with TREANDA. Combination therapy, progressive disease or reactivation of hepatitis B were confounding factors in some patients. Most cases were reported within the first three months of starting therapy. Monitor liver chemistry tests prior to and during bendamustine therapy.
Other Malignancies: There are reports of pre-malignant and malignant diseases that have developed in patients who have been treated with TREANDA, including myelodysplastic syndrome, myeloproliferative disorders, acute myeloid leukemia, and bronchial carcinoma.
Extravasation Injury: TREANDA extravasations have been reported in postmarketing resulting in hospitalizations from erythema, marked swelling, and pain. Assure good venous access prior to starting TREANDA infusion and monitor the intravenous infusion site for redness, swelling, pain, infection, and necrosis during and after administration of TREANDA.
Embryo-fetal Toxicity: TREANDA can cause fetal harm when administered to a pregnant woman. Women should be advised to avoid becoming pregnant while using TREANDA.
Most Common Adverse Reactions:
The most common non-hematologic adverse reactions for CLL (frequency ≥15%) are pyrexia, nausea, and vomiting.
The most common non-hematologic adverse reactions for NHL (frequency ≥15%) are nausea, fatigue, vomiting, diarrhea, pyrexia, constipation, anorexia, cough, headache, weight decreased, dyspnea, rash, and stomatitis.
The most common hematologic abnormalities for both indications (frequency ≥15%) are lymphopenia, anemia, leukopenia, thrombocytopenia, and neutropenia.
TO REPORT ADVERSE REACTIONS: Contact us at 1-800-896-5855 or [email protected]
Please see Full Prescribing Information for TREANDA (bendamustine HCl) Injection
TRISENOX (arsenic trioxide) Injection
Indication
TRISENOX is indicated for induction of remission and consolidation in patients with acute promyelocytic leukemia (APL) who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy, and whose APL is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression.
Important Safety Information for TRISENOX (arsenic trioxide) Injection
WARNING: APL DIFFERENTIATION SYNDROME, CARDIAC CONDUCTION ABNORMALITIES, AND ELECTROLYTE MONITORING
APL Differentiation Syndrome: Patients with APL treated with TRISENOX have experienced symptoms similar to a syndrome called the retinoic-acid-Acute Promyelocytic Leukemia (RA-APL) or APL differentiation syndrome, characterized by fever, dyspnea, weight gain, pulmonary infiltrates and pleural or pericardial effusions, with or without leukocytosis. This syndrome can be fatal. High-dose steroids have been administered at the first suspicion of the APL differentiation syndrome and appear to mitigate signs and symptoms. At the first signs that could suggest the syndrome (unexplained fever, dyspnea and/or weight gain, abnormal chest auscultatory findings or radiographic abnormalities), immediately initiate high-dose steroids (dexamethasone 10 mg intravenously BID), irrespective of the leukocyte count, and continue for at least 3 days or longer until signs and symptoms have abated. The majority of patients do not require termination of TRISENOX therapy during treatment of the APL differentiation syndrome.
Cardiac Conduction Abnormalities: Before initiating therapy, perform a 12-lead ECG, assess serum electrolytes and creatinine, correct preexisting electrolyte abnormalities, and consider discontinuing drugs known to prolong QT interval. Arsenic trioxide can cause QT interval prolongation and complete atrioventricular block. QT prolongation can lead to a torsade de pointes-type ventricular arrhythmia, which can be fatal. The risk of torsade de pointes is related to the extent of QT prolongation, concomitant administration of QT prolonging drugs, a history of torsade de pointes, preexisting QT interval prolongation, congestive heart failure, administration of potassium-wasting diuretics, or other conditions that result in hypokalemia or hypomagnesemia. One patient (also receiving amphotericin B) had torsade de pointes during induction therapy for relapsed APL with arsenic trioxide.
Contraindications: TRISENOX is contraindicated in patients who are hypersensitive to arsenic.
APL Differentiation Syndrome: Nine of 40 patients with APL treated with TRISENOX, at a dose of 0.15 mg/kg, experienced the APL differentiation syndrome.
Cardiac Conduction Abnormalities: Torsade de Pointes, Complete Heart Block, and QT Prolongation: Sixteen of 40 patients (40%) had at least one ECG tracing with a QTc interval greater than 500 msec. Prolongation of the QTc was observed between 1 and 5 weeks after TRISENOX infusion, and then returned towards baseline by the end of 8 weeks after TRISENOX infusion. Monitor ECG weekly and more frequently for clinically unstable patients. For QTc greater than 500 msec, complete corrective measures and reassess the QTc with serial ECGs prior to initiating TRISENOX. During TRISENOX therapy, maintain potassium concentrations above 4 mEq/L and magnesium concentrations above 1.8 mg/dL. Reassess patients who reach an absolute QT interval value > 500 msec and immediately correct concomitant risk factors, if any, while the risk/benefit of continuing versus suspending TRISENOX therapy should be considered. The risk may be increased when TRISENOX is coadministered with medications that can lead to electrolyte abnormalities (such as diuretics or amphotericin B).
Carcinogenesis: The active ingredient of TRISENOX, arsenic trioxide, is a human carcinogen. Monitor patients for the development of second primary malignancies.
Embryo-Fetal Toxicity: TRISENOX can cause fetal harm when administered to a pregnant woman. One patient who became pregnant while receiving arsenic trioxide had a miscarriage. Advise pregnant women of the potential risk to a fetus. Advise females and males of reproductive potential to use effective contraception during and after treatment with TRISENOX.
Lactation: TRISENOX is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants, discontinue breastfeeding during treatment with TRISENOX.
Laboratory Tests: Electrolyte and glucose levels, as well as hepatic, renal, hematologic, and coagulation profiles should be monitored at least twice weekly, and more frequently for clinically unstable patients during the induction phase and at least weekly during the consolidation phase.
Drug Interactions: Avoid the concomitant use of TRISENOX with medications that can prolong the QT/QTc interval or those that can lead to electrolyte abnormalities. Concomitant use of drugs that can prolong the QT/QTc interval with TRISENOX may increase the risk of serious QT/QTc interval prolongation. Electrolyte abnormalities increase the risk of serious QT/QTc interval prolongation. Monitor ECGs and electrolytes more frequently in patients who are unable to avoid concomitant use of these medications and TRISENOX.
Pediatric Use: In a pediatric study, the toxicity profile observed in 13 pediatric patients with APL between the ages of 4 and 20 receiving TRISENOX was similar to that observed in adult patients. Additional drug-related toxicities reported included: gastrointestinal disorders, metabolic and nutrition disorders, respiratory disorders, cardiac failure congestive, neuralgia, and enuresis. One case each of pulmonary edema and caecitis were considered serious reactions. No children less than 4 years of age were enrolled in the trial due to the rarity of APL in this age group.
Patients with Renal Impairment: Exposure of arsenic trioxide may be higher in patients with severe renal impairment. Patients with severe renal impairment (creatinine clearance less than 30 mL/min) should be monitored for toxicity when these patients are treated with TRISENOX, and a dose reduction may be warranted. The use of TRISENOX in patients on dialysis has not been studied.
Patients with Hepatic Impairment: Since limited data are available across all hepatic impairment groups, caution is advised in the use of TRISENOX in patients with hepatic impairment. Monitor patients with severe hepatic impairment (Child-Pugh Class C) who are treated with TRISENOX for toxicity.
Most Common Adverse Reactions: Most patients experienced some drug related toxicity, most commonly leukocytosis, gastrointestinal (nausea, vomiting, diarrhea, and abdominal pain), fatigue, edema, hyperglycemia, dyspnea, cough, rash or itching, headaches, and dizziness. These adverse effects have not been observed to be permanent or irreversible nor do they usually require interruption of therapy.
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Please see Full Prescribing Information for TRISENOX (arsenic trioxide) Injection