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.