Tag Archives: CLL

ASH 2013

ash2013

The ASH 2013 (American Society of Hematology) annual meeting kicks off in New Orleans today. There will be many presentations; this one I am most eagerly awaiting. It presents current data on the Infinity Pharmaceuticals ipi-145 clinical trial I am enrolled in. The presenter, Dr Ian Flinn is my Hematologist/Oncologist. You can read the full abstract here. Here’s a tidbit.

#677 Preliminary Safety and Efficacy Of IPI-145, a Potent Inhibitor Of Phosphoinositide-3-Kinase-δ,γ, In Patients With Chronic Lymphocytic Leukemia

Program: Oral and Poster Abstracts
Type: Oral
Session: 642. CLL: Therapy, excluding Transplantation: Clinical Trials of B Cell Receptor Signaling Inhibitors
Monday, December 9, 2013: 5:30 PM
295-296 (Ernest N. Morial Convention Center)

Ian Flinn, MD, PhD1, Manish Patel, MD1,2*, Brad S. Kahl, MD3, Steven M. Horwitz, MD4, Francine M. Foss, MD5, Yasuhiro Oki, MD6, Pierluigi Porcu, MD7, Jennifer Sweeney, BS8*, Kerstin Allen, MA8*, Kerrie Faia, MS8*, Patricia Harris, MPH8*, Joi Dunbar, PharmD8*, Howard M. Stern, M.D., Ph.D.8*, Patrick Kelly, MD8 and Susan O’Brien, MD6

Clinical activity has been observed in R/R CLL pts at all doses of IPI-145 studied from 8 mg to 75 mg BID and in pts with R/R high-risk disease (TP53 mut/17pdel).  Treatment-related lymphocytosis is rapid, with the median ALC return to baseline within 6 cycles of treatment.  Reduction in adenopathy occurs early with no apparent dose-dependence.  Nodal responses (>50% reduction in adenopathy by CT assessment) occurred in 79% of pts after 2 treatment cycles.  Best overall response (based on investigator assessment per IWCLL) in evaluable pts to date (median [range] number of cycles 5.1 [1-21.1]) is 52%, with 1 CR, 15 PR, 14 SD and 1 PD. The ORR for the 19 evaluable pts treated at ≤25 mg BID is 53% (10/19; including 1 CR) and 7 of the 8 SD pts achieving nodal response.  Resolution of lymphocytosis may lead to an increase in best ORR for SD pts who remain on study.  R/R pts with high-risk disease (TP53 mut/17pdel) had similar ORR.
Conclusions:  IPI-145, an oral, potent PI3K-δ,γ inhibitor, appears well tolerated and has shown promising clinical activity in pts with R/R CLL across the range of doses examined.  The PK/PD and clinical activity suggest that 25 mg BID is a biologically active dose in R/R CLL, and this dose has been selected for an upcoming randomized Phase 3 trial in R/R CLL. Updated data from treatment-naïve CLL pts who received IPI-145 at 25 mg BID and R/R CLL pts who received IPI-145 at 25 mg and 75 mg BID will be presented.

Staging CLL

Soft_ruler

Oncologists use a standard staging system to assign a number (1-4) or measure to the degree of advancement of a cancer case. Different cancer types have different metrics. In most cancers, stage 4 indicates metastasis has already occurred; in other words the cancer/tumor cells have spread to and affected other tissues away from where they began to grow. Since CLL generally doesn’t form tumors and doesn’t usually metastasize, stage four has a different meaning here. I was stage 4 before I began treatment. RAI staging is more common in the USA. Here is an explanation via the Luekemia & Lymphoma Society.

Doctors use staging to help them predict chronic lymphocytic leukemia’s (CLL’s) progression and develop an appropriate treatment plan. Doctors use one of two staging systems: the Rai staging system or the Binet staging system.
Staging systems consider certain factors such as:

  • the elevation of your blood and marrow leukemic lymphocyte counts
  • your lymph nodes’ size and distribution
  • your spleen’s size
  • the extent of your decreased blood platelet counts
  • the degree of anemia

RAI Staging System

The Rai staging system classifies CLL into the following five stages based on factors at the time of diagnosis:

Low-Risk 0
  • Abnormal increase in the number of lymphocytes in the blood and marrow
Intermediate
Risk I
  • Abnormal increase in the number of lymphocytes in the blood and marrow
  • Enlarged (swollen) lymph nodes
Intermediate
Risk II
  • Abnormal increase in the number of lymphocytes in the blood and marrow
  • Enlarged (swollen) lymph nodes, liver or spleen
High Risk III
  • Abnormal increase in the number of lymphocytes in the blood and marrow
    Low platelet count
  • Abnormal increase in the number of lymphocytes in the blood and marrow
    Low platelet count
High Risk IV
  • Abnormal increase in the number of lymphocytes in the blood and marrow
  • Low platelet count

Happy Thanksgiving

turkey-dinnerAs we celebrate Thanksgiving Day here in the US, I want to share my gratitude for this difficult but good year. In the middle of the hardships have been many blessings.

  • To my Lord Jesus and Father God for keeping me going each day and somehow always providing for all my needs
  • My family and friends for their unwavering love and support.
  • To the entire team at Sarah Cannon Research Institute / Tennessee Oncology / Sarah Cannon Center for Blood Cancers for helping start to beat this wretched leukemia into retreat.
  • To all my new friends and family at Middle Tennessee Camp Bluebird for their cheer, support and love.

Cycle 4

drop-kick

I’ve now completed 3 28 day treatment cycles in the Phase 1 clinical trial for IPI-145. Most of my blood counts with the frequent exception of the neutrophils have been rebounding steadily. Most are back to where they were in May 2013, 3 months before I began treatment. The initial goal was to drop-kick this CLL. So far, we seem to be doing just that.

Hopeful CLL commentary from Dr Bruce Cheson

Here’s a snippet from his post about the upcoming ASH (American Society of Hematology) conference in New Orleans, LA in December. My own doc, Dr Ian Flinn will be presenting on trial data with ipi-145. I can’t wait. There is a video on page one but the audio did not play well for me. Here’s page three from the article

Bumper Crop of New Agents

The rest of the studies focus on the new agents. We have several ibrutinib trials, including a single-agent study in patients with or without 17p deletion. There will be the final analysis of bendamustine and rituximab plus ibrutinib.[13] Do you need the chemotherapy? Do you need the bendamustine? There will be another abstract[14] with rituximab and ibrutinib alone.

This isn’t the only exciting drug. There are phosphoinositide (PI) 3-kinase inhibitors, which appear to be very good and are very impressive, perhaps as good as ibrutinib when you combine them with a drug like rituximab. In fact, a recent study of rituximab-idelalisib vs rituximab-placebo was closed early because of a survival advantage.

We are also going to be seeing a list of new PI 3-kinase inhibitors for the treatment of CLL: a new delta inhibitor, a new gamma inhibitor, and others. We’ll have to see which of these provides an advantage over the others, if at all. But in any event, we have great new drugs that will be changing the landscape of non-Hodgkin lymphomas, Hodgkin lymphoma, and chronic lymphocytic leukemia.

This is Bruce Cheson, signing off for Medscape Hematology. I will be back with you after the ASH meeting in New Orleans. See you there. Goodbye.

Partial Remission?

Screenshot from 2013-11-20 14:18:59

From what I’ve read, this seems to be the minimum goal for success in treatment of this CLL but a definition has eluded me until now. According to the journal “blood” 2008 111: 5446-5456 Prepublished online January 23, 2008;doi:10.1182/blood-2007-06-093906 it is:

5.2. Partial remission (PR)
PR is defined by the criteria described in sections 5.2.1, 5.2.2, or
5.2.3 (if abnormal before therapy), as well as one or more of the
features listed in section 5.2.4. To define a PR, these parameters need to be documented for a minimal duration of 2 months (Table
4). Constitutional symptoms persisting for more than 1 month
should be recorded.
5.2.1. A decrease in the number of blood lymphocytes by 50%
or more from the value before therapy.
5.2.2. Reduction in lymphadenopathy (by CT scans in clinical
trials 57 or by palpation in general practice) as defined by the
following:
5.2.2.1. A decrease in lymph node size by 50% or more either in
the sum products of up to 6 lymph nodes, or in the largest diameter
of the enlarged lymph node(s) detected prior to therapy.
5.2.2.2. No increase in any lymph node, and no new enlarged
lymph node. In small lymph nodes (< 2 cm), an increase of less
than 25% is not considered to be significant.
5.2.3. A reduction in the noted pretreatment enlargement of
the spleen or liver by 50% or more, as detected by CT scan (in
clinical trials) or palpation (in general practice).
5.2.4. The blood count should show one of the following
results:
5.2.4.1. Neutrophils more than 1.5 ϫ 109/L (1500/uL) without need for exogenous growth factors.
5.2.4.2. Platelet counts greater than 100 ϫ 109/L (100,000/uL) or 50% improvement over baseline without need for exogenous growth factors.
5.2.4.3. Hemoglobin greater than 110 g/L (11.0 g/dL) or 50%
improvement over baseline without requiring red blood cell
transfusions or exogenous erythropoietin.

Failure is not an option! We are going to get there and hope and pray for eventual full remission.

Go Fish?

FISH_technique

Yesterday, I posted about a diagnostic test used for CLL called flow cytometry. Another modern test that is also used extensively is known as FISH (Fluorescence In Situ Hybridization). Like flow cytometry, it is also a fairly expensive test to have run. According to WebMD:

How FISH Works

During a FISH test using a sample of the patient’s tissue, special colored dyes are attached to specific parts of certain chromosomes in order to visualize and count them under a fluorescent microscope and to detect cancer-promoting abnormalities.

Abnormalities found in cancer cells include:

  • Translocation. Part of one chromosome has broken off and relocated itself onto another chromosome.
  • Inversion. Part of a chromosome is in reverse order although it is still attached to the correct chromosome.
  • Deletion. Part of a chromosome is missing.
  • Duplication. Part of a chromosome has been copied and the cell contains too many copies.

Translocations can help doctors identify some types of leukemia, lymphomas, and sarcoma. Duplications in breast cancer cells can help doctors choose optimal treatments.

Compared to standard cytogenetic (cell gene) tests, one advantage of FISH is that it can identify genetic changes that are too small to be seen under a microscope. Another advantage is that FISH doesn’t have to be performed on cells that are actively dividing. Because other tests cannot be performed until cancer cells have been growing in lab dishes for about two weeks, the process usually takes about three weeks. FISH results are usually available within a few days.

Wikipedia has a good article on Fluorescence In Situ Hybridization if you’re interested (or having trouble sleeping).

Flow Cytometry

I got an invoice a few days ago for the latest series of flow cytometry tests. Unfortunately, these blood tests tend to be really expensive. This is a modern diagnostic method which counts individual cell types for genetic testing to classify a case of CLL and identify its potential prognostic factors via Fluorescence Activated Cell Sorting (FACS). Here’s a good introductory video that explains the process.

This article also has some good basic info if you are interested. LINK