Combination Therapy Could Dramatically Alter CLL Treatment

MedicalResearch.com Interview with:

Dr. Danelle James,

Dr. James

Dr. Danelle James, M.D., M.A.S.
Head of Clinical Science
Pharmacyclics, an AbbVie Company

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: CAPTIVATE is a Phase 2 study investigating IMBRUVICA (ibrutinib) plus VENCLEXTA (venetoclax) for the treatment of Chronic Lymphocytic Leukemia (CLL) in the first-line setting. It was designed to evaluate if remission with undetectable minimal residual disease (MRD) can provide treatment-naïve CLL/SLL patients with treatment holidays (a period of time when a patient is able to stop therapy). The study enrolled 164 patients with previously untreated CLL or SLL.

In preclinical and ongoing clinical studies, we’ve seen complementary activities with this combination. The combination has also previously shown potential for deeper remissions, as well as potential for lower risk of tumor lysis syndrome with ibrutinib as the lead-in therapy.

Early data from CAPTIVATE show promising activity for the combination in this patient population, with 77 percent of the first 30 patients achieving responses with no detectable MRD in the blood after only six cycles of the combination therapy. Approximately nine out of 10 of the first patients achieved undetectable MRD after 12 cycles of combination therapy (which were preceded by three cycles of single agent ibrutinib, for a total of 15 cycles of therapy). Specifically, 86 percent of the first 14 patients achieved undetectable MRD in the marrow and 93 percent in the peripheral blood.

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Engineered Single Cell ‘Cured’ Patient of CLL

MedicalResearch.com Interview with:

Dr. J Joseph Melenhorst, PhD Director, Product Development & Correlative Sciences laboratories (PDCS) Adjunct Associate Professor Penn Medicine Center for Cellular Immunotherapies University of Pennsylvania

Dr. Melenhorst

Dr. J Joseph Melenhorst, PhD
Director, Product Development & Correlative Sciences laboratories (PDCS)
Adjunct Associate Professor
Penn Medicine
Center for Cellular Immunotherapies
University of Pennsylvania

MedicalResearch.com: What is the background for this study? Would you briefly explain what is meant by CLL and CAR T cells? 

Response: We started treating patients with a form of blood cancer called CLL (chronic lymphocytic leukemia) using a form of gene therapy wherein we engineer the patient’s own immune cells – T cells – with a tumor targeting molecule: The CAR, which stands for chimeric antigen receptor. When we engineer the patient’s immune cells we use a vehicle, in this case virus, that inserts the payload – the CAR – into the patient’s DNA. The virus disappears, and the CAR stays. Where this CAR inserts itself is unpredictable, but we always get stably engineered cells.  Continue reading

Cost and Side Effects Influence Patients’ Preferences for Leukemia Medications

MedicalResearch.com Interview with:

Carol Mansfield, PhD, Senior Research Economist Health Preference Assessment RTI Health Solutions www.rtihs.org

Dr. Mansfield

Carol Mansfield, PhD,
Senior Research Economist

Health Preference Assessment
RTI Health Solutions
www.rtihs.org 

MedicalResearch.com: What is the background for this study?

Response: As the most prevalent form of leukemia, chronic lymphocytic leukemia (CLL) affects approximately 130,000 people in the United States. More than 20,000 new cases are diagnosed each year. In recent years, more treatment options–each with its own associated benefits, side effects, and price tag–have been approved. This leaves patients and physicians with a variety of factors they must consider when choosing a treatment plan.

While every patient wants the most effective drug with the fewest side effects, most people don’t have that option available. By asking patients to make tradeoffs and rank their preferences, we can form an understanding of how patients approach their treatment.

This study showed that patients with CLL value medicines that provide the longest progression-free survival, but are willing to trade some benefits for a lower risk of serious adverse events. Additionally, we found that cost clearly has an impact on which treatment a patient would choose. When patients get prescribed something they can’t afford, they are forced to make very difficult choices.

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CLL: Long-term efficacy of ONO/GS-4059 is maintained without emergence of new toxicities

MedicalResearch.com Interview with:

Martin J.S. Dyer, D.Phil MA FRCP FRCPath Ernest and Helen Scott Haematological Research Institute University of Leicester, UK

Prof. Dyer

Martin J.S. Dyer, D.Phil MA FRCP FRCPath
Ernest and Helen Scott Haematological Research Institute
University of Leicester, UK

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: This study follows on from a world-first clinical trial of a new drug to treat particular blood cancers. Results of that international clinical trial were published in the journal Blood in November 2015 and looked at the efficacy of a new inhibitor, ONO/GS-4059, in the treatment of CLL and Non-Hodgkin Lymphoma patients, refractory or resistant to current chemotherapies.

ONO/GS-4059 targets BTK, a protein essential for the survival and proliferation of the tumour cells.

The study opened in January 2012 and 90 patients were enrolled in different centres in the UK and in France, with 28 coming from Leicester. Patients with CLL showed the best response and most of them were still on the study after 3 years, and remarkably without notable toxicities.

In the new paper, we are reporting the long-term follow-up results. This work, published in the journal Blood, was funded by the Ernest and Helen Scott Haematological Research Institute, ONO Pharmaceuticals, Gilead Pharmaceuticals and the Cancer Research UK Leicester Experimental Cancer Medicine Centre. Local charity Hope Against Cancer fund the Clinical Trials Facility based at the Leicester Royal Infirmary.

This current paper describes the long term follow up and shows that in patients with CLL the remissions are durable and associated with no new toxicities. Furthermore, in collaboration with Sistemas Genomicos, a company in Valencia, we have shown that mutations associated with aggressive disease respond well to treatment with ONO/GS-4059.

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