Combination of Ibrutinib, Rituximab Induced Responses in High-Risk CLL

Editor’s note: This article discusses the results of a clinical trial—a research study with volunteer patients. The goal of the trial is to test a new treatment for high-risk chronic lymphocytic leukemia (CLL). The treatment combines two drugs, ibrutinib and rituximab. Patients participating in the trial have had promising responses to the treatment. Further studies will continue to evaluate the new treatment.

“Patients with high-risk chronic lymphocytic leukemia demonstrated encouraging rates of objective response and durable remission after treatment with ibrutinib plus rituximab, according to results of a single-center phase 2 study.

“Jan A. Burger, MD, PhD, associate professor in the department of leukemia at The University of Texas MD Anderson Cancer Center, and colleagues assessed the activity and safety of ibrutinib (Imbruvica; Pharmacyclics, Janssen), a Bruton’s tyrosine kinase inhibitor, in combination with the chimeric monoclonal antibody rituximab (Rituxan; Genentech, Biogen Idec) in 40 adults with high-risk CLL.

“All patients either experienced short PFS — defined as less than 36 months — after first-line chemoimmunotherapy, or they demonstrated high-risk cytogenetic abnormalities, such as deletion 17p, deletion 11q or TP53 mutation…

“ ‘From this study, can we state that the time for ibrutinib monotherapy is over, and that combination with anti-CD20 antibodies the preferential treatment partner, as is the case for idelalisib (Zydelig, Gilead)?’ Ghia wrote. ‘Despite [these] promising results, we will probably need to wait. Short follow-up of only 18 months makes it difficult to ascertain whether an actual benefit in PFS or OS exists when compared with the monotherapy regimen. The clinical advantage of adding a second drug (rituximab) needs to be consistently proven because of the relevant economic consequences: The additional cost of combinations might jeopardize the overall sustainability of future treatments.’ ”

Clinical Trial to Test Safety of Drug Targeting Leukemia Cells

Editor’s note: Researchers have launched a new clinical trial—a research study with volunteer patients—to test a new drug to treat chronic lymphocytic leukemia (CLL). The drug is called cirmtuzumab (also known as UC-961). It targets a protein called ROR1, which is only found in tumors and helps them grow and metastasize. The researchers will enroll 33 to 78 patients with relapsed or refractory (does not respond to treatment) CLL, who will be treated with cirmtuzumab in San Diego.

“Researchers at the University of California, San Diego School of Medicine, in partnership with the California Institute for Regenerative Medicine (CIRM) and Celgene Corporation, a New Jersey-based biopharmaceutical company, have launched a phase 1 human clinical trial to assess the safety and efficacy of a novel monoclonal antibody for patients with chronic lymphocytic leukemia (CLL).

“CLL is the most common form of blood cancer in adults, with more than 15,000 new cases diagnosed each year in the United States. The new antibody targets ROR1, a protein used by embryonic cells during early development that is also exploited by cancer cells to promote tumor growth and metastasis – the spreading of cancer throughout the body that is responsible for 90 percent of all cancer-related deaths.

“ROR1 is not expressed by normal adult cells, making it a specific marker of cancer cells in general and cancer stem cells in particular. Because ROR1 is a primary driver of tumor growth and metastasis, researchers believe it presents an excellent target for anti-cancer therapy.

“Developed at UC San Diego Moores Cancer Center by Thomas Kipps, MD, PhD, who holds the Evelyn and Edwin Tasch Chair in Cancer Research, and colleagues, the antibody is called cirmtuzumab (also known as UC-961). In previous animal studies, Kipps’ team reported that ROR1 is singularly expressed on CLL and also on a variety of different cancers, including cancers of the breast, pancreas, colon, lung and ovary. In mouse models of CLL, ROR1 acts as an accelerant when combined with another oncogene to produce a faster-growing, more aggressive cancer.”

With So Many Terrific New Drugs For Chronic Lymphocytic Leukemia, Why Worry?

“It’s hard to keep track of practice-changing drugs for chronic lymphocytic leukemia (CLL). Since last November, the FDA has approved three new agents and expanded indications for another to treat this indolent cancer of white blood cells. As someone who spent over ten years studying this form of leukemia, I’m thrilled by the science behind these targeted medicines, and by the potentially life-saving new options for people with this condition.

“But perhaps a dose of caution is due. With so many neat, targeted drugs available, some oncologists and hematologists (blood specialists) may be too ready, or eager, to treat CLL in in early-stage cases when a “watch and wait” approach might be best. Until recent years, with few drugs to offer, observation was standard for most CLL patients without symptoms. Many did fine for years and even decades, without any intervention.

“Now, with effective treatments in-hand, waiting becomes the challenge. It can be nerve-wracking for patients with early-stage disease who, upon hearing of these new CLL drugs, may understandably say ‘let’s get on with it.’ As an oncologist, persuading a CLL patient who lacks symptoms or other reasons to intervene that they don’t need treatment yet – and convincing them sufficiently that they won’t just go and find another doctor who will treat them, soon – is generally a lot harder than just prescribing medication.”

New Ways to Treat Solid Tumours

Editor’s note: Recent research has uncovered a potential new way to fight some cancer types. The key is a protein called Eph3A, which is made by the cells of blood cancers and solid tumors. Researchers made a new drug called KB004 to target and kill cells with Eph3A. The drug is currently being tested in a clinical trial with volunteer leukemia patients.

“An international team of scientists has shown that an antibody against the protein EphA3, found in the micro-environment of solid cancers, has anti-tumour effects.

“As EphA3 is present in normal organs only during embryonic development but is expressed in blood cancers and in solid tumours, this antibody-based approach may be a suitable candidate treatment for solid tumours…

“Currently, KaloBios Pharmaceuticals is testing the anti-EphA3 antibody KB004 in a multi-centre Phase I/II clinical trial in Melbourne and the US in patients with EphA3 expressing blood malignancies: AML, MDS and myelofibrosis.”

FDA Expands Approved Use of Imbruvica for Chronic Lymphocytic Leukemia

Editor’s note: When a drug company creates a new cancer treatment, the treatment must be approved by the U.S. Food and Drug Administration (FDA) before doctors in the U.S. can prescribe it. An FDA approval for a new drug usually specifies the particular kinds of patients who are allowed to be treated. A drug called Imbruvica was recently FDA-approved for treating people with chronic lymphocytic leukemia (CLL) who have been previously but unsuccessfully treated with at least one other drug. Now, the FDA has also approved Imbruvica for people with CLL whose tumors have a genetic mutation called del 17p, as detected by molecular testing. People with this mutation are less likely to have success with standard CLL treatments, so Imbruvica could be a good alternative.

“The U.S. Food and Drug Administration today expanded the approved use of Imbruvica (ibrutinib) to treat patients with chronic lymphocytic leukemia (CLL) who carry a deletion in chromosome 17 (17p deletion), which is associated with poor responses to standard treatment for CLL. Imbruvica received a breakthrough therapy designation for this use.

“The FDA is also approving new labeling to reflect that Imbruvica’s clinical benefit in treating CLL has been verified. In February 2014, Imbruvica received accelerated approval to treat CLL based on its effect on overall response rate. New clinical trial results examining progression-free survival and overall survival have confirmed the drug’s clinical benefit.

“A type of non-Hodgkin lymphoma, CLL is a rare blood and bone marrow disease that usually gets worse slowly over time, causing a gradual increase in white blood cells called B lymphocytes, or B cells. The National Cancer Institute estimates that 15,720 Americans will be diagnosed and 4,600 will die from CLL in 2014. Imbruvica works by blocking the enzyme that allows cancer cells to grow and divide.”

Roche's Gazyvaro Approved in Europe for Patients with the Most Common Type of Leukemia

Editor’s note: A new treatment for chronic lymphocytic leukemia (CLL) has been approved in Europe, meaning that oncologists in Europe can now start prescribing it to their patients. The treatment is specifically meant for people with CLL who have not yet been treated but who have other conditions that make them unable to use standard full-dose fludarabine-based treatment. The new treatment combines a drug called Gazyvaro with the chemotherapy drug chlorambucil. Gazyvaro is an immunotherapy drug, meaning that it boosts a patient’s own immune system to fight cancer.

“Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the European Commission has approved Gazyvaro (obinutuzumab) in combination with chlorambucil chemotherapy for the treatment of people with previously untreated chronic lymphocytic leukemia who have comorbidities making them unsuitable for an intensive therapy (full-dose fludarabine based therapy). Outside of the EU and Switzerland, Gazyvaro is marketed as Gazyva.

“ ‘We are proud to make Gazyvaro available for CLL patients in Europe,’ said Sandra Horning, M.D., Roche’s Chief Medical Officer and Head, Global Product Development. ‘Gazyvaro is a new option that helps patients achieve deep responses to treatment that translate to longer lasting remissions.’ ”

“The European approval was based on the outcomes of the CLL11 study which was conducted in close collaboration with the German CLL Study Group. The study showed that Gazyvaro plus chlorambucil met its primary endpoint by significantly reducing the risk of disease worsening or death by 61% compared to MabThera/Rituxan plus chlorambucil (progression free survival; PFS). For patients in the Gazyvaro arm, median PFS was 26.7 months compared with 15.2 months for those in the MabThera/Rituxan arm (HR 0.39, CI 0.31-0.49, p<0.001).

“Additional Gazyvaro data from the CLL11 study showed higher complete response rates (21% compared with 7%) and a ten-fold increase in the percentage of people achieving minimal residual disease (MRD) negativity* (37.7% compared with 3.3%) compared to the MabThera/Rituxan arm of the study.”

FDA Approves Zydelig for Three Types of Blood Cancers

“The U.S. Food and Drug Administration today approved Zydelig (idelalisib) to treat patients with three types of blood cancers.

“Zydelig is being granted traditional approval to treat patients whose chronic lymphocytic leukemia (CLL) has returned (relapsed). Used in combination with Rituxan (rituximab), Zydelig is to be used in patients for whom Rituxan alone would be considered appropriate therapy due to other existing medical conditions (co-morbidities). Zydelig is the fifth new drug with breakthrough therapy designation to be approved by the FDA and the third drug with this designation approved to treat CLL.

“The FDA is also granting Zydelig accelerated approval to treat patients with relapsed follicular B-cell non-Hodgkin lymphoma (FL) and relapsed small lymphocytic lymphoma (SLL), another type of non-Hodgkin lymphoma. Zydelig is intended to be used in patients who have received at least two prior systemic therapies.

“ ‘In less than a year, we have seen considerable progress in the availability of treatments for chronic lymphocytic leukemia,’ said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. ‘Zydelig’s approval to treat CLL reflects the promise of the breakthrough therapy designation program and represents the FDA’s commitment to working cooperatively with companies to expedite a drug’s development, review and approval.’ ”

New Test Predicts Survival in Blood Cancer Patients

New test predicts survival in blood cancer patients

“Scientists have developed a test which accurately predicts the prognosis for patients with the most common form of leukaemia.

“The findings could also inform the development of a prognostic test for patients with other forms of cancer.

“Researchers from the School of Medicine used pioneering techniques for measuring the length and function of tiny structures known as ‘telomeres’ – repeating sections of DNA found at the ends of chromosomes.

“They used these techniques to determine if the telomeres were working or not in cells from patients with chronic lymphocytic leukaemia (CLL). Patients with short dysfunctional telomeres displayed a considerably poorer clinical outcome compared to those with long and functional telomeres.”

Chemotherapy-Free Combo Is Tested in CLL

“A novel immune-based combination therapy for the initial treatment of chronic lymphocytic leukemia (CLL) does not appear to improve on results achieved with established regimens that include chemotherapy.

“In a phase 2 study, investigators combined rituximab (Rituxan, MabThera and Roche), the monoclonal antibody widely used for CLL, and lenalidomide (Revlimid, Celgene), an immunomodulatory agent that is not approved in these patients.

“The idea behind the pairing was to avoid chemotherapy, which is generally not well tolerated by older or infirm CLL patients and is part of all regimens containing rituximab, say the investigators, led by Danelle James, MD, from the Moores Cancer Center at the University of California, San Diego.”

Editor’s note: A potential alternative to chemotherapy for chronic lymphocytic leukemia (CLL) was tested in volunteer patients, but did not show improved results over chemo. The treatment combines the drug Rituxan with another drug called Revlimid, which is meant to boost a patient’s immune system to help fight cancer. Researchers hope to test other combinations of non-chemo drugs to see if they will prove more successful.