ASH 2013 Video WIth Andrew Schorr

This was a video we did at ASH in December prior to the approval of ibrutinib.  At the time, we didn't know the terminology the FDA would use to describe its "approval."

The main topic of discussion in this video is primarily how a patient goes about choosing a therapy in CLL.  In many cases patients will feel comfortable with a physician recommendation, in other cases they may want to educate themselves about all their options and make their own choice.

In the midst of new treatments like ibrutinib, idelalisib, ABT-199, Gazyva etc. that can be bewildering. Not sure if this video helps sort it out or not, but it is short and hopefully worth your time

Irbrutinib has been approved in CLL

IBRUTINIB HAS BEEN APPROVED IN CLL
IBRUTINIB HAS BEEN APPROVED IN CLL
IBRUTINIB HAS BEEN APPROVED IN CLL
IBRUTINIB HAS BEEN APPROVED IN CLL
IBRUTINIB HAS BEEN APPROVED IN CLL
IBRUTINIB HAS BEEN APPROVED IN CLL


Here is the press release from ASCO:



From the American Society of Clinical Oncology
In cooperation with the Food and Drug Administration (FDA), and as a service to our members, ASCO will periodically distribute information about newly approved therapies for cancer patients.  This helps FDA to inform oncologists and professionals in oncology-related fields of recent approvals in a timely manner.  Included in the email from the FDA will be a link to the product label, which will provide the relevant clinical information on the indication, contraindications, dosing, and safety.  In sending this information, ASCO does not endorse any product or therapy and does not take any position on the safety or efficacy of the product or therapy described.  The following is a message from the FDA's Office of Hematology and Oncology Products Director, Dr. Richard Pazdur:

On February 12, 2014, the U. S. Food and Drug Administration granted accelerated approval to ibrutinib (IMBRUVICA, Pharmacyclics, Inc.) for the treatment of patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy.  Ibrutinib previously received accelerated approval on November 13, 2013 for the treatment of patients with mantle cell lymphoma who have received at least one prior therapy.
The approval in CLL was based on the results of a multi-center, single-arm trial of 48 patients with previously treated CLL. The median age was 67 years (range, 37 to 82 years) and 71% were male. All patients had a baseline ECOG performance status of 0 or 1. The median time since diagnosis was 6.7 years and the median number of prior treatments was 4 (range, 1 to 12 treatments).  Ibrutinib was administered orally at 420 mg once daily until disease progression or unacceptable toxicity.

The efficacy results demonstrated a 58.3% overall response rate (95% CI: 43.2, 72.4) as assessed by an independent review committee.  No complete responses were observed. The response duration ranged from 5.6 to 24.2+ months; the median was not reached.

The safety profile of ibrutinib for patients with previously treated CLL was consistent with observations in the mantle cell lymphoma clinical trial.  The most common adverse reactions reported in the CLL clinical trial (occurring in greater than or equal to 20% of patients) were thrombocytopenia, diarrhea, bruising, neutropenia, anemia, upper respiratory tract infection, fatigue, musculoskeletal pain, rash, pyrexia, constipation, peripheral edema, arthralgia, nausea, stomatitis, sinusitis, and dizziness.

As a condition of this accelerated approval, the FDA required that the sponsor submit results of randomized clinical trial(s.) In January 2014, Pharmacyclics notified FDA of the early stopping of the RESONATE trial by the Data Monitoring Committee (DMC) based on favorable results of a planned interim analysis. RESONATE, a phase 3 clinical trial, randomized patients to either ibrutinib or ofatumumab.  Patients entered on this trial had previously treated CLL or small lymphocytic lymphoma (SLL) and were not considered candidates for treatment with purine analogue-based treatments.  The trial was reported to demonstrate an improvement in progression-free survival and overall survival.  

The recommended dose and schedule of ibrutinib for patients with CLL is 420 mg (three 140 mg capsules) taken orally once daily.
Full prescribing information is available at: 
http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/203147s000lbl.pdf

Management of High Risk CLL

There are a variety of organizations out there that help disseminate education material.  I have recently had the option to work with a group called "Clinical Care Options."  I gave a seminar for them at ASH on Diffuse Large B Cell Lymphoma and more recently they asked me to put together a module for patients with high risk CLL (link here).

"High Risk CLL" isn't a really tightly defined term although there does seem to be some consensus that it may define a group of patients at high risk of dying from their disease within a few years.  It can refer to patients with high risk genetic markers such as 17P deletion or mutations like BIRC3.  It can refer to patients who fail to achieve a really good response to therapy and have high levels of "minimal residual disease."  It can also refer to patients who relapse quickly after initial therapy.  Though there is probably quite a bit of overlap between these sorts of patients (ie. the patients with bad markers, fail to respond well and relapse early) those relationships are only still just becoming more clear (see my post on CLL prognosis).

Anyhow, I wanted to provide you with a link to the education module.  You need to sign up for a free account which takes about 10 seconds to do.  I hope it is a good tutorial for physicians who take care of patients with CLL.  I acknowledge that it is fairly technical for patients who are new to CLL but each of the concepts have been presented previously on my blog.

Thanks for reading