Patients with chronic myeloid leukemia (CML) or acute lymphoblastic leukemia that carries the Philadelphia chromosome (Ph+ALL) who can't tolerate the targeted drugs that revolutionized care for these leukemias now have three new options.

The U.S. Food and Drug Administration (FDA) has approved  three new drugs in the past few months. Ponatinib (Iclusig) was approved last week, an effective drug for many patients with  treatment-resistant disease. This comes on the heels of approvals of bosutinib (Bosulif) in September and omacetaxine (Synribo) in October.

Patients with both leukemias have enjoyed strong responses to imatinib (Gleevec) and second-generation drugs nilotinib (Tasigna) and dasatinib (Sprycel).  All work by inhibiting proteins called tyrosine kinases on leukemia cells, in particular the aberrant BCR-ABL protein that causes these diseases.

However, 30-40 percent of patients' CML resists imatinib. Nilotinib and dasatinib work for about 40-50 percent of those patients.

"It's important to have as many therapies against cancer as we can, because rarely does one drug or combination succeed for all patients," said Jorge Cortes, M.D., professor in MD Anderson's Department of Leukemia.  "These new drugs cover different gaps in treatment, so they can serve our patients in different ways."

Trusting neighbors and community may aid smoking cessation in African-American smokers, accordingly to a study published in the Annals of Behavioral Medicine, a publication of the Society of Behavioral Medicine.

MD Anderson researchers collected data from 397 African-Americans seeking treatment to quit smoking to determine if there was a significant relationship between social cohesion and smoking cessation. The study examined if social cohesion -- the self-reported connectedness and trust felt between neighbors -- was directly linked to smoking abstinence in African-American smokers actively trying to quit, and if psychosocial mediators played a role in those relations.

"We know from previous research that despite later smoking initiation and a lower rate of smoking, African-American smokers are more likely to develop smoking-related diseases and to die from them than are Caucasians," said Lorraine Reitzel, Ph.D., assistant professor in the Department of Health Disparities Research at MD Anderson Cancer Center.  "Investigating factors that affect smoking cessation within this population is important to increase our understanding of how to reduce smoking-related health disparities among this group."

More than 45,000 African-Americans die in the United States from smoking related cancers per year.

Pre-quit, quit-day and post-quit

Participants were followed over a six-month period during three stages of the study: pre-quit, quit-day and post-quit. During the first stage, data was collected on demographics including educational level and employment status, as well as tobacco dependence, so that known effects of these things on smoking cessation could be controlled for in the data analyses.

The MCL study was the third of the meeting presented by MD Anderson faculty about ibrutinib.  The others were in combination for chronic lymphocytic leukemia and by itself for relapsed or resistant follicular lymphoma.  

"I believe we are witnessing a breakthrough in mantle cell lymphoma. This is great news for patients," said Michael Wang, M.D., associate professor in MD Anderson's Departments of Lymphoma and Myeloma and Stem Cell Transplantation and Cellular Therapy. Wang is lead author of the study.

Wang, director of the mantle cell lymphoma (MCL) program at MD Anderson, has spent the past 12 years researching the disease, including clinical trials of proteasome inhibitors, immune-modulating agents and an mTOR inhibitor.

"In a heavily treated relapsed or refractory population, oral ibrutinib induced a response rate as high as 70% - better than any other single agent ever tested in MCL," he said. "The response is durable with a long progression-free survival."

A new technique for expanding blood stem cells from umbilical cords in the lab before transplanting them into a patient reduces the perilous time it takes for the new blood supply to take hold.

Cord blood transplants provide a source of blood stem cells to cancer patients who need a transplant after high-dose chemotherapy for leukemia, lymphoma and other malignancies but cannot find a matched donor. 

This is particularly true for people of Latino, African or Asian heritage, who are underrepresented in the bone marrow donor pool, which makes it hard to find a matched blood stem cell donor.

"Pre-transplant cord blood expansion on mesenchymal precursor cells could become the new standard of care if our findings are confirmed in a randomized clinical trial," said Elizabeth Shpall, M.D., professor in the Department of Stem Cell Transplantation and Cellular Therapy.  She is principal investigator of an early stage clinical trial and senior author of a paper published this week in the New England Journal of Medicine.

Umbilical cords provide a much lower dose of cells than those given by a matched donor whose stem cells are taken from the bone marrow or circulating blood. The result: slower establishment of the new blood supply, particularly white cells (neutrophils) and platelets, exposing patients to greater risk of infection and bleeding.

Shpall and colleagues show how expanding one of the two cords on a bed of supportive  in the lab increases the number of cells transplanted and the speed of establishment (engraftment) of white cells and platelets for the patient over those who get the usual unexpanded double cord transplant. 

A drug approved for treating resistant versions of two types of lymphoma knocked down the disease in all 26 patients evaluated in a phase I clinical trial of front line use combined with chemotherapy.

Michelle Fanale, M.D., assistant professor in MD Anderson's Department of  Lymphoma and Myeloma presented results of the trial at the 54th American Society of Hematology Annual Meeting and Exposition in Atlanta.

The trial provides evidence that the drug brentuximab vedotin (ADCETRIS, developed by Seattle Genetics, Inc.) potentially could be brought forward to front line treatment and could be used to treat additional types of non-Hodgkin lymphoma.

A combination of brentuximab vedotin with a chemotherapy combination called CHP produced complete remissions in 23 of the 26 patients, who had either systemic anaplastic large cell lymphoma (19 patients)  or a CD30-positive mature T cell or natural killer cell lymphoma (seven patients).  The other three had partial remissions.

All seven of the mature T cell or natural killer cell lymphoma patients had a complete remission.

Updated: 4:30 p.m. Friday, Dec. 14

The U.S. Food and Drug Administration approved ponatinib (Iclusig) for chronic myeloid leukemia and Philadelphia chromsome-positive acute lymphoblastic leukemia today.

Sunday began with a news briefing about a promising phase II trial for ponatinib, a chronic myeloid leukemia investigational drug that  helps patients who are resistant to existing CML drugs.

Jorge Cortes, M.D., professor in the Department of Leukemia, presented the phase II data at the 54th American Society of Hematology Annual Meeting and Exposition  less than two weeks after the phase I results were published in the New England Journal of Medicine.

The new, larger trial also shows ponatinib sparks responses in patients with the T315I mutation and other drug-resistant mutations.

T315I is present in up to 20 percent of patients and blocks the docking station where three other successful CML drugs (Gleevec, Sprycel and Tasigna)  normally connect to the mutant protein. Patients in the trial have had at least two of these drugs fail.

At 15.3 months of median follow up for patients in the initial, chronic phase of CML, 149 or 267 (54%) had a major cytogenetic response (reduction of CML cells in the blood) and 46% had a complete cytogenetic response (no CML cells in the bone marrow).

Of 64 chronic phase CML patients with the T315I mutation, 45 (70%) achieved major cytogenetic response with 66% reaching complete cytogenetic response.

Elnar Koseoglu of Physician Relations and Bradley Swinney of Banner MD Anderson await the afternoon rush at booth 3500 in the exhibition hall at the 54th ASH Annual  Meeting and Exposition.

Occupying prime corner real estate right by a pizza parlor in the massive hall, the MD Anderson Physican Relations   booth had 225 physician visitors by early afternoon. With scientists and physicians in lectures and seminars most of the day, traffic is feast (during breaks) or famine.

MD Anderson faculty are always a major, influential presence at ASH, the world's premier meeting about the science and diseases of the blood.

New drugs could spell end of chemo for chronic lymphocytic leukemia

Jan Burger, M.D., associate professor in the Department of Leukemia, spoke at the meeting's first news briefing for journalists early Saturday.

His clinical trial of the drug ibrutinib combined with rituximab (Rituxan) for high-risk CLL patients with resistant disease attracted attention because 38 of 40 patients were still on the drug and in remission at four months.Side effects have been mild.

"Although this study has a short follow-up time so far, we're encouraged that the vast majority of patients are responding and can continue treatment," Burger said. "We still need long-term follow up to see if the remissions are durable and the low toxicity endures." 

The high-risk patients in the clinical trial are essentially out of treatment options.   

Rituximab is thought to block a resistance mechanism to ibrutinib. Earlier and ongoing clinical studies by MD Anderson and other research teams indicate ibrutinib alone is highly effective for patients with lower risk disease.  

Chemotherapy combinations are curative for most CLL patients, but the harsh treatment can lead to lethal secondary cancers for some.

For more details, see the MD Anderson news release about the study and the ASH study abstract (click OK at the opening page and you'll get to the abstract.) CLL is one of the eight cancers targeted by MD Anderson's  Moon Shots Program.

Burger presents his findings to other scientists and physicians Sunday afternoon. 

By Will Fitzgerald, MD Anderson Staff Writer

Fifty years from now when an author is compiling a review of modern cancer therapy for a historical publication, he'll undoubtedly recognize the accomplishments of Gabriel Hortobagyi, M.D., a visionary cancer physician and researcher whose discoveries saved countless women from breast cancer.

He first became familiar with the disease walking the hallways of an Ohio hospital during his internal medicine residency. Hortobagyi was intrigued by the opportunity to help patients conquer a disease that posed more questions than answers.  More than 40 years later, this pursuit still passionately consumes his career as a physician in MD Anderson's Department of Breast Medical Oncology and through collaborations around the world.

Today, at the 35th annual San Antonio Breast Cancer Symposium, Hortobagyi was presented with the William L. McGuire Memorial Lecture Award for his outstanding achievements.

"It's very humbling and gratifying to be selected by one's peers because everyone on the selection committee is a very accomplishment individual," Hortobagyi said.  "It's very meaningful for me, and, of course, it's recognition of our group's accomplishments."

Two papers published by MD Anderson clinical researchers are included in the American Society of Clinical Oncology's report, Clinical Cancer Advances 2012: ASCO's Annual Report on Progress Against Cancer.

The world's largest oncology organization annually conducts an independent review of advances in clinical cancer research in the past year that have the greatest potential to improve patients' survival and quality of life.  The report is compiled under the guidance of 21 experts in specific areas of cancer research.

MD Anderson's publications addressed serous ovarian carcinoma, the most difficult-to-treat version of that cancer, and chronic myeloid leukemia.

Study titles and principal investigators are
:
Jorge Cortes, M.D., professor in MD Anderson's Department of Leukemia, "A pivotal phase II trial of ponatinib in patients with CML and Ph+ALL resistant or intolerant to dasatinib or nilotinib, or with the T315I mutation."  Presented at the ASCO 2012 annual meeting, data show ponatinib, a third-generation tyrosine kinase inhibitor, acts against disease with specific resistance mutations that other drugs are usually unable to reach.

Yuexin Liu, Ph.D., instructor in MD Anderson's Department of Pathology, "Integrated Analysis of Gene Expression and Tumor Nuclear Image Profiles Associated with Chemotherapy Response in Serous Ovarian Carcinoma."  Published in  PLOS One in May 2012, this study found a genetic signature that accurately predicts chemotherapy response in serous ovarian cancer.

The report is available online and an interactive version with illustrations, sources and additional information is available at http://www.cancerprogress.net/latest_advances.html