The FDA on February 12, 2014 granted accelerated approval to IMBRUVICA® for the treatment of patients with Chronic Lymphocytic Leukemia (CLL) who have received at least one prior therapy. The FDA initially granted accelerated approval in November, 2013, for the treatment of patients with Mantle Cell Lymphoma (MCL) who have received at least one prior therapy. IMBRUVICA® is an oral capsule and is a product of Pharmacyclics, Inc.
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Maintenance treatment with capecitabine and bevacizumab versus observation after induction treatment with chemotherapy and bevacizumab in metastatic colorectal cancer (mCRC) The phase III CAIRO3 study of the Dutch Colorectal Cancer Group (DCCG)
SUMMARY: Treatment of metastatic colorectal cancer with a combination of chemotherapy given along with AVASTIN® is well established. However the duration of therapy remains unclear and it is common to give drug holidays to patients. The outcome in patients who are given these drug holidays remains unclear. The CAIRO3 study is a phase III trial in which patients with previously untreated, unresectable metastatic colorectal cancer received induction treatment with six cycles of Capecitabine (XELODA®)/Oxaliplatin (ELOXATIN®) plus Bevacizumab (AVASTIN®) – CAPOX-B. Patients who had not progressed during induction and had reponses or had stable disease (N=558) were then randomized to receive either XELODA® at 625 mg/m2 twice daily along with AVASTIN® at 7.5 mg/kg every 3 weeks or be observed. Upon first progression, patients in both treatment groups were treated with CAPOX-B until second progression and this was considered the primary endpoint for this study. Secondary endpoints included Overall Survival (OS). Median follow up was 40 months. The median time to second progression from randomization was 19.8 months in the maintenance group and 15 months in the observation group (HR=0.63; P<0.001) The time to first progression in the maintenance treatment group was 8.5 months versus 4.1 months in the observation group (HR 0.41; P<0.001). The time to second progression following treatment with CAPOX-B was 11.8 months in the maintenance group versus 10.5 months for the observation group (HR 0.77; P=0.007), representing a 23% reduction in the risk of progression. The adjusted median OS was 21.7 months with maintenance treatment and 18.2 months in the observation group (HR=0.80; P=0.035). Treatment was well tolerated with slight increase in hand-foot syndrome and neurotoxicity in the maintenance group. Based on this data, the authors recommended maintenance treatment with XELODA® and AVASTIN® until progression or unacceptable toxicity, following 6 cycles of efficacious treatment with CAPOX-B. It is important to note that in the SAKK 41/06 trial conducted by the Swiss Group, observation alone was non-inferior to single agent maintenance AVASTIN® following initial chemotherapy, suggesting that the addition of fluoropyrimidine (XELODA®) chemotherapy to AVASTIN® as maintenance treatment, improves time to progression and median OS in patients with metastatic colorectal cancer. Koopman M, Simkens LH, Ten Tije, AJ et al. J Clin Oncol 31, 2013 (suppl; abstr 3502)
Clinical Cancer Advances 2013 Annual Report on Progress Against Cancer From the American Society of Clinical Oncology
SUMMARY: Immune checkpoints are cell surface inhibitory proteins/receptors that harness the immune system and prevent uncontrolled immune reactions. Immune checkpoints are an area of increasing interest as they utilize the patient’s immune system to reject cancer cells. Survival of cancer cells in the human body may be to a significant extent, related to their ability to escape immune surveillance, by inhibiting T lymphocyte Activation .
The T cells of the immune system play a very important role in modulating the immune system. EFFECTOR T cells include Cytotoxic T cells, Helper T cells, and Natural Killer (NK) cells, that enable the immune system to destroy cancer cells and pathogens. The REGULATORY T cells however, suppress immune response. Under normal circumstances, inhibition of an intense immune response and switching off the EFFECTOR T cells of the immune system, is an evolutionary mechanism and is accomplished by Immune checkpoints or gate keepers. The mechanism can be compared to a lock and key where the appropriate Ligand (KEY) binds to the Immune checkpoint protein/receptor (LOCK) and activates or inhibits a T lymphocyte. With the ongoing understanding of tumor immunology and the recognition of Immune checkpoint proteins, researchers have focused on the development of antibodies that either target the membrane bound inhibitory Immune checkpoint proteins/receptors such as CTLA-4, PD-1, IDO, etc. (LOCK) or target the inhibitory soluble Ligands or antigens that are located on the surface of certain cancer cells (KEY) that bind to these Immune check point proteins/receptors. By doing so, one would expect to unleash the EFFECTOR T cells resulting in T cell proliferation, activation and a therapeutic response. The first immune checkpoint protein to be clinically targeted was CTLA-4. YERVOY® (Ipilimumab), an antibody that blocks Immune checkpoint protein/receptor CTLA-4, was approved by the FDA in March 2011 and has been shown to prolong overall survival in patients with previously treated unresectable or metastatic melanoma. The next immune check point protein/receptor studied for targeted therapy was PD-1. Lambrolizumab (MK-3475) is a humanized anti–PD-1 monoclonal antibody that demonstrated a 38% rapid and durable response rate and a more than 7 month median progression-free survival in patients with advanced melanoma, regardless of their prior therapy with YERVOY®. Nivolumab, another PD-1 targeted antibody demonstrated remarkable efficacy in a Phase I study with an overall response rate of 30%, median survival of 16.8 months and a 2 year survival of 44%. Based on this provocative data, a combination of Nivolumab and YERVOY® were studied in patients with advanced Stage III or IV melanoma who had received up to three prior therapies.. The idea was to block both the Immune checkpoints, PD-1 and CTLA-4, for improved efficacy. Fifty three (N=53) patients were treated with a combination of these two agents and 33 patients received these agents sequentially. Indeed, the highest response rate was over 50% in the combination group with 30% of these patients experienced a more than 80% response rate at 12 weeks of treatment whereas the response rate in the sequential treatment group was 20%. This preliminary study confirmed that blocking multiple Immune checkpoint proteins/receptors may result in rapid and durable responses in patients with advanced malignant melanoma. Phase III studies are underway to confirm this efficacy data and this concept is also being studied in other tumor types. Targeting/inhibiting the ligands (KEY) and preventing their binding to the Immune checkpoint protein/receptor, is another approach to stimulate antitumor immune response. PD-L1 protein (Ligand) which is often elevated in melanoma tumor cells, bind to PD-1 check point protein/receptor and can inhibit T cells and escape immune surveillance. An investigational PD-L1 targeted (Ligand targeted) engineered antibody (MPDL3280A) demonstrated a rapid response in 26% of the 45 patients with metastatic melanoma and the benefit was more so in those tumors expressing PD-L1. Promising activity has also been seen in advanced renal cell carcinoma. Antibodies targeting the Immune checkpoint receptor/protein or the Ligands binding to these receptors, are being developed, to carry payloads that are lethal to the checkpoint protein/receptor or Ligand. In conclusion, identifying as well as inhibiting certain Immune checkpoint proteins/receptors and/or Ligands that bind to these receptors, may give us new insights in the field of tumor immunology, resulting in better outcome for our cancer patients. Patel JD, Krilov L, Adams S, et al. J Clin Oncol 2013;32:129-160
Sorafenib in locally advanced or metastatic patients with radioactive iodine-refractory differentiated thyroid cancer The phase III DECISION trial
SUMMARY: Over 90% of all Thyroid cancers are classified as Differentiated Thyroid Cancers (DTC) with Papillary, Follicular and Hürthle cell histologies. Approximately 5% to 15% of these patients develop resistance to RadioActive Iodine (RAI). NEXAVAR® is a multi-targeted tyrosine kinase inhibitor and prevents cancer growth by inhibiting multiple kinases that are involved in cell proliferation and angiogenesis. These kinases include Raf, VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-B, KIT, FLT-3 and RET.
The DECISION trial is a randomized, double-blind, multicenter phase III study in which the efficacy and safety of NEXAVAR® was compared with placebo, in patients with progressive RAI-refractory DTC. Four hundred and seventeen patients (417) were randomized to receive either NEXAVAR® 400 mg PO BID (n=207) or placebo (n=210). The median age was 63 yrs and only patients who had no prior chemotherapy or targeted therapy and with disease progression within the preceding 14 months, were included. Over 95% of the patients had metastatic disease and the most common sites of spread were lungs and lymph nodes. Treatment was continued until disease progression or until unacceptable toxicity was noted. Upon progression, patients in the placebo group were allowed to crossover and receive open-label NEXAVAR®. The primary endpoint was Progression Free Survival (PFS). Secondary endpoints included Overall Survival (OS), Response Rate (RR=Complete + Partial Response [PR]), and safety. The median PFS was 10.8 months with NEXAVAR® compared to 5.8 months with placebo (hazard ratio [HR] = 0.58; P <0.0001). Partial responses were observed in 12.2% of patients receiving NEXAVAR® compared with 0.5% in the placebo arm (P < 0.0001). The median duration of partial response was 10.2 months. Further, 42% of patients in the NEXAVAR® group had stable disease for 6 months or more compared to 33% in the placebo group. Median OS has not been reached. It should be noted that approximately 70% of patients in the placebo group were allowed to crossover to receive open-label NEXAVAR® and this could impact the OS data. The most common adverse events in the NEXAVAR® group included hand–foot skin reactions, diarrhea, rash/desquamation, fatigue and hypertension. The authors concluded that NEXAVAR® nearly doubled the PFS compared to placebo, in this select group of patients with advanced DTC and is the first and only FDA approved therapy for Differentiated Thyroid Cancers. Brose MS, Nutting C, Jarzab B, et al. J Clin Oncol 31, 2013 (suppl; abstr 4)
Sorafenib in locally advanced or metastatic patients with radioactive iodine-refractory differentiated thyroid cancer The phase III DECISION trial
SUMMARY: Over 90% of all Thyroid cancers are classified as Differentiated Thyroid Cancers (DTC) with Papillary, Follicular and Hürthle cell histologies. Approximately 5% to 15% of these patients develop resistance to RadioActive Iodine (RAI). NEXAVAR® is a multi-targeted tyrosine kinase inhibitor and prevents cancer growth by inhibiting multiple kinases that are involved in cell proliferation and angiogenesis. These kinases include Raf, VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-B, KIT, FLT-3 and RET. 
The DECISION trial is a randomized, double-blind, multicenter phase III study in which the efficacy and safety of NEXAVAR® was compared with placebo, in patients with progressive RAI-refractory DTC. Four hundred and seventeen patients (417) were randomized to receive either NEXAVAR® 400 mg PO BID (n=207) or placebo (n=210). The median age was 63 yrs and only patients who had no prior chemotherapy or targeted therapy and with disease progression within the preceding 14 months, were included. Over 95% of the patients had metastatic disease and the most common sites of spread were lungs and lymph nodes. Treatment was continued until disease progression or until unacceptable toxicity was noted. Upon progression, patients in the placebo group were allowed to crossover and receive open-label NEXAVAR®. The primary endpoint was Progression Free Survival (PFS). Secondary endpoints included Overall Survival (OS), Response Rate (RR=Complete + Partial Response [PR]), and safety. The median PFS was 10.8 months with NEXAVAR® compared to 5.8 months with placebo (hazard ratio [HR] = 0.58; P <0.0001). Partial responses were observed in 12.2% of patients receiving NEXAVAR® compared with 0.5% in the placebo arm (P < 0.0001). The median duration of partial response was 10.2 months. Further, 42% of patients in the NEXAVAR® group had stable disease for 6 months or more compared to 33% in the placebo group. Median OS has not been reached. It should be noted that approximately 70% of patients in the placebo group were allowed to crossover to receive open-label NEXAVAR® and this may impact the OS data. The most common adverse events in the NEXAVAR® group included hand–foot skin reactions, diarrhea, rash/desquamation, fatigue and hypertension. The authors concluded that NEXAVAR® nearly doubled the PFS compared to placebo, in this select group of patients with advanced DTC and is the first and only FDA approved therapy for Differentiated Thyroid Cancers. Brose MS, Nutting C, Jarzab B, et al. J Clin Oncol 31, 2013 (suppl; abstr 4)
Enzalutamide in men with chemotherapy-naive metastatic prostate cancer (mCRPC) Results of phase III PREVAIL study
SUMMARY: Prostate Cancer is driven by androgens (primarily testosterone) and androgen signaling pathways. There is evidence to suggest that prostate cancer cells continue to depend on androgen receptor (AR) signaling even in an androgen-deprived environment. Therefore, targeting AR and AR signaling pathways remains a rational approach in the treatment of Castration Resistant Prostate Cancer (CRPC). The first generation anti-androgen agents such as EULEXIN® (Flutamide), CASODEX® (Bicalutamide) and NILANDRON® (Nilutamide) act by binding to the Androgen Receptor (AR) and prevent the activation of the AR and subsequent up-regulation of androgen responsive genes. They may also accelerate the degradation of the AR. These agents have a range of pharmacologic activity from being pure anti-androgens to androgen agonists.
XTANDI® (Enzalutamide) is a second-generation anti-androgen with no reported agonistic effects. It competitively inhibits androgens and AR binding to androgens as well as AR nuclear translocation and interaction with DNA. It thus inhibits several steps in the AR signaling pathway. XTANDI® was first approved by the FDA in 2012, for the treatment of patients with metastatic CRPC who have previously received TAXOTERE® (Docetaxel) based chemotherapy. The PREVAIL study is a double-blind, placebo-controlled, phase III trial in which 1,717 chemotherapy-naive patients with mCRPC (metastatic Castrate Resistant Prostate Cancer) were randomly assigned 1:1 to receive either XTANDI® 160 mg/day or placebo. Prior treatment with surgery or radiation therapy for their primary tumor, as well as hormonal intervention with a LHRH (Luteinizing Hormone Releasing Hormone) agonist or first-generation anti-androgen was allowed. The two co-primary endpoints were Overall Survival (OS) and radiographic Progression Free Survival (rPFS), as measured by bone scans and CT scans. At the time of preplanned interim analysis, XTANDI® demonstrated a statistically significant benefit over placebo with a 30% reduction in risk of death (OS: HR= 0.70; P< 0.0001) and an 81% reduction in risk of radiographic Progression Free Survival (rPFS: HR 0.19; P< 0.0001). Further, the response rates were meaningful with 20% complete responses and 39% partial responses (59% Response Rate) compared with 5% Response Rate in the placebo group (P<0.0001). XTANDI® also significantly delayed the median time to chemotherapy by 17 months compared with those who took placebo (P<0.0001). Based on the results of this interim analysis, the Independent Data Monitoring Committee recommended stopping the study and allowing patients in the placebo group to receive XTANDI®. XTANDI® was well tolerated and the most common side effects were hot flashes, weight gain, fatigue, constipation, back and joint pain. The authors concluded that XTANDI® significantly improves OS and rPFS in patients with chemotherapy-naive mCRPC and can significantly delay the need for chemotherapeutic intervention. Beer TM, Armstrong AJ, Sternberg CN, et al. J Clin Oncol 32, 2014 (suppl 4; abstr LBA1)
Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II) an international, double-blind, randomised placebo-controlled trial
SUMMARY: NOLVADEX® (Tamoxifen) is a Selective Estrogen Receptor Modulator (SERM), approved by the FDA to also reduce the incidence of breast cancer in women considered to be at high risk (ChemoPrevention). This agent however has been linked to endometrial cancer and thromboembolic phenomenon in some women. ARIMIDEX® is a non-steroidal Aromatase Inhibitor proven to be more efficacious than NOLVADEX® both in metastatic and adjuvant settings. Similar to NOLVADEX®, ARIMIDEX® also prevents the occurrence of new primary tumors in the contralateral breast, in postmenopausal females. With this background, the International Breast Cancer Intervention Study (IBIS) -II trial enrolled 3864 postmenopausal women considered to be at increased risk of breast cancer and randomized them to receive either ARIMIDEX® (Anastrazole) 1 mg QD (N=1920) or Placebo QD (N=1944)for 5 years. Patients were considered to be at high risk if they had a family history of breast cancer, atypical ductal hyperplasia, lobular carcinoma in-situ or dense breast tissue. The median age was 59 years. The primary end point was histologically confirmed Invasive breast cancer or Ductal Carcinoma In- Situ. At a median follow up of 5 years, the incidence of breast cancer in the ARIMIDEX® group was 2% and in the placebo group was 4%. The predicted cumulative incidence of breast cancer after 7 years was 2.8% in the ARIMIDEX® group and 5.6% in the placebo group (HR=0.47; P<0.0001). This represented a 53% reduction in the risk of breast cancer. The adverse events were comparable in both groups with slight increase in the musculoskeletal and vasomotor events noted in the ARIMIDEX® group. The authors concluded that ARIMIDEX® reduced the risk of primary breast cancer by more than 50% in high risk postmenopausal women. Other unrelated studies have shown that acceptance of breast cancer prevention with medications (ChemoPrevention) appeared to be related to education and income, putting emphasis on education and adequate counseling of women, considered to be at high risk. Cuzick J, Sestak I, Forbes JF, et al. The Lancet, Early Online Publication, 12 December 2013
Ruxolitinib for Myelofibrosis – An Update of Its Clinical Effects
SUMMARY: MyeloFibrosis (MF) is a MyeloProliferative Neoplasm (MPN) characterized by a ineffective hematopoiesis, progressive fibrosis of the bone marrow and potential for leukemic transformation. This stem cell disorder is Philadelphia Chromosome negative and manifestations include anemia, splenomegaly and related symptoms such as abdominal distension and discomfort with early satiety. Cytokine driven debilitating symptoms such as fatigue, fever, night sweats, weight loss, pruritus and bone or muscle pain can further impact an individual’s quality of life. Myelofibrosis can be primary (PMF) or secondary to Polycythemia Vera (PV) or Essential Thrombocythemia (ET). The JAK-STAT signaling pathway has been implicated in the pathogenesis of Myelofibrosis. 
This pathway normally is responsible for passing information from outside the cell through the cell membrane to the DNA in the nucleus for gene transcription. Janus Kinase (JAK) family of tyrosine kinases are cytoplasmic proteins and include JAK1, JAK2, JAK3 and TYK2. JAK1 helps propagate the signaling of inflammatory cytokines whereas JAK2 is essential for growth and differentiation of hematopoietic stem cells. These tyrosine kinases mediate cell signaling by recruiting STAT’s (Signal Transducer and Activator of Transcription), with resulting modulation of gene expression. In patients with MPN, the aberrant myeloproliferation is the result of dysregulated JAK2-STAT signaling as well as excess production of inflammatory cytokines associated with this abnormal signaling. These cytokines contribute to the symptoms often reported by patients with MF. JAK2 mutations such as JAK2 V617F are seen in approximately 60% of the patients with PMF and ET and 95% of patients with PV. Unlike CML where the BCR-ABL fusion gene triggers the disease, JAK2 mutations are not initiators of the disease and are not specific for MPN. Further, several other genetic events may contribute to the abnormal JAK2-STAT signaling. JAKAFI® is a potent JAK1 and JAK2 inhibitor and exerts its mechanism of action by targeting and inhibiting the dysregulated JAK2-STAT signaling pathway. The FDA approval of JAKAFI® for the treatment of Intermediate and high risk Myelofibrosis was based on 2 phase III trials – COMFORT (Controlled Myelofibrosis Study with Oral JAK1/JAK2 Inhibitor Treatment) – I and COMFORT-II studies. In COMFORT-I study, 309 intermediate or high risk patients were randomized to receive either JAKAFI® (N=155) or Placebo (N=154). The primary end point of a 35% or more reduction in spleen size at 24 weeks was noted in 42% of those who received JAKAFI® vs 0.7% in the placebo group (P<0.0001). Most patients in the JAKAFI® group had some reduction in the spleen volume whereas majority of those in the placebo arm had increase in splenomegaly. There was a 46% reduction in the TSS (Total Symptom Score) at week 24 in the JAKAFI® group compared to 5% in the placebo group and majority of patients in the later group had worsening of symptoms (P<0.0001). When JAKAFI® was compared to Best Available Therapy (BAT) in the COMFORT-II study, 28% of the patients in the JAKAFI® group met the primary endpoint of a 35% or more reduction in the spleen volume at 48 weeks compared to none in the BAT group (P<0.0001). Over 55% had a mean decrease in spleen size in the JAKAFI® compared to a 4% mean increase in the BAT group. The 2 year follow up analyses from both these trials showed improved overall survival and a reduction in the risk of death for patients randomized to JAKAFI®, compared to those in the control groups. There was weight gain with alleviation of cachexia and improvements in splenomegaly and symptoms were durable. This benefit was seen in patients regardless of JAK mutations. It remains to be seen if JAKAFI® will benefit patients with Polycythemia Vera and Essential Thrombocythemia. Kantarjian HM, Silver RT, Komrokji RS, et al. Clinical Lymphoma Myeloma and Leukemia 2013; 13:638-645
Randomized Open-Label Phase II Study of Decitabine in Patients With Low- or Intermediate-Risk Myelodysplastic Syndromes
SUMMARY: The MyeloDysplastic Syndromes (MDS) are disorders of hematopoietic stem cells, characterized by one or more peripheral blood cytopenias. These syndromes may arise de novo or can be secondary, following treatment with chemotherapy and/or radiation therapy for other malignancies. It can also manifest after environmental exposures. The International Prognostic Scoring System (IPSS), based on the score, divides patients with MDS into Lower Risk (IPSS low and intermediate-1 scores) and Higher Risk (IPSS intermediate-2 and high scores) groups. This classification remains arbitrary because of the heterogeneity in the Lower Risk group and poor outcomes in certain Lower Risk subset of patients. DACOGEN® (Decitabine) exerts its antineoplastic effects by inhibitng DNA methyltransferase, resulting in hypomethylation of DNA and apoptosis. The authors in this Phase II study evaluated the outcomes in patients with Low or Intermediate-1 risk MDS using lower doses of DACOGEN® given subcutaneously on two different treatment schedules. Of the 67 randomized patients, 43 patients received DACOGEN® 20mg/m2 SC QD for three consecutive days every 28 days (Schedule A) or 20mg/m2 SC given on days 1, 8 and 15, of a 28 day cycle (Schedule B). Treatment was planned for up to one year. Primary endpoint was Overall Improvement Rate (OIR) and this included Complete Remission (CR), Partial Remission (PR), marrow CR or Hematologic Improvement (HI). Secondary end points included HI, transfusion independence, cytogenetic response, overall survival (OS), and time to acute myeloid leukemia or death. Taken as a group, there was no difference in the OIR (23%), HI, transfusion independence or cytogenetic response between schedule A and schedule B. However, patients on schedule A had more CR's making this a protocol defined superior schedule. Median OS was not reached. Transfusion independency was noted in 67% of the patient's on schedule A and 59% of the patient's on schedule B. Further, approximately 70% of the patients were alive at 500 days. The most frequent adverse events in schedule A and B were anemia (23% vs 18%), neutropenia (28% vs 36%) and thrombocytopenia (16% vs 32%). Based on these promising results, the authors recommended DACOGEN® given on three consecutive days SC every 28 days as per Schedule A, for patients with Low or Intermediate-1 risk MDS. Garcia-Manero G, Jabbour E, Borthakur G, et al. J Clin Oncol 2013;31:2548-2553
Effect of NPM1 and FLT3 Mutations on the Outcomes of Elderly Patients With Acute Myeloid Leukemia Receiving Standard Chemotherapy
SUMMARY: Cytogenetic analysis has been part of routine evaluation when caring for patients with AML. By predicting resistance to therapy, cytogenetics stratify patients based on risk and helps manage them accordingly. Even though normal karyotype is the most common cytogenetic finding, approximately 10%-15% of AML patients have a monosomal karyotype (presence of at least 2 autosomal monosomies or a single autosomal monosomy in combination with at least one structural abnormality). These patients have a poor prognosis and alterations in the TP53 gene has been implicated in majority of these patients. AML patients with a normal karyotype should be tested for NPM1 (Nucleophosmin), FLT3 (Fms-related tyrosine kinase 3) and CEBPA (CCAAT/Enhancer Binding Protein Alpha) mutations, in addition to cytogenetics, as this may have therapeutic implications. CEBPA is a transcription factor and plays an important role in myeloid differentiation. Mutations in the CEBPA gene have been described in approximately 10% of patients with AML. Patients can have one or two mutations in this gene. It appears that favorable outcomes may be limited to those patients who have double CEBPA mutations rather than those with single CEBPA mutations. AML patients without FLT3 mutations or NPM1 mutation with CEBPA-double mutations have a favorable outcome. In this retrospective review, the authors analyzed the clinical impact of NPM1 and FLT3 mutations in AML patients, 65 years of age or older, treated with cytotoxic chemotherapy. A total of 557 patients were retrospectively reviewed. They noted that the outcomes were significantly better amongst patients with NPM1-mut/FLT3-wild type genotype compared to any other NPM1/FLT3 genotypes. The median survival was 21.5 months vs. 9.0 months and estimated 2-year survival rates were 51% vs. 38%, respectively (P = .003). The authors concluded that elderly AML patients with NPM1-mut/FLT3-wild type genotype have significantly improved outcomes when treated with cytotoxic chemotherapy. This subset of patients have a good prognosis with outcomes similar to those with favorable cytogenetics such as Inversion 16 and t(8:21). The discovery of molecular mutations is providing valuable information to facilitate risk-adapted therapy. Daver N, Liu Dumlao T, Ravandi F, et al. Clinical Lymphoma Myeloma and Leukemia 2013;13:435-440
