ASH 2018: Asciminib (ABL001) early-phase data of CML patients with T315I mutation
With five approved tyrosine kinase inhibitors (TKIs) and none of them being curative, one may think whether there are still gaps to be filled with new CML drugs that follow similar mechanisms of action and not a totally different approach to eradicate the disease.
There is still a proportion of CML patients that does not respond to current TKIs properly or cannot tolerate them – and with non-effective treatment, they are at risk of life-threatening disease progression. Some CML patients sadly can’t access current 2nd generation TKI (Dasatinib, Nilotinib, Bosutinib) or 3rd generation (Ponatinib) drugs even if they would potentially address unmet medical need, e.g. in case of multi-resistent mutations. Additionally, about one third of CML patients achieve a good response on current TKIs but never get into MR4 remission, so they will not be able to try treatment-free remission (TFR) – so a more potent drug would probably increase “TFR probability” . There is also some concern on all current 2nd generation TKI about side effects, e.g. cardiovascular side effects or pleural effusions, so a highly effective drug with a more favourable long-term toxicity profile and a better quality of life is certainly something CML patients would like to see. Of course the ultimate goal is cure of CML, which none of the current drugs achieve.
One new but also non-curative option is now on the horizon with Asciminib, formerly called ABL001, which was presented by Prof Delphine Réa from the Hôpital Saint-Louis, Paris, France at the ASH congress this year. Asciminib is in a way similar to other TKI, as it inhibits the CML-specific BCR-ABL and stops the proliferation of the CML cells. However, called an “allosteric inhibitor”, it binds at a different site of the protein than any of the other TKIs, and hence is not affected by the known mutations of the ATP pocket that actually render the current TKIs ineffective.
ASH 2018 CML Oral and Poster sessions
- ASH 2018 - CML Advocates Network Report by Giora Sharf -
Every year in the last years I have been asked by Haematologists and also patients, why do I leave home for 6 days and fly across the world to ASH in the USA, as CML seems to be a conquered disease where the life expectancy of a patient is similar to a healthy person. When I think about it I have a few possible answers.
First, ASH is the biggest and most important hematologic conference of the year where the newest data from clinical trials and real life are published at thousands of abstracts and posters in different sessions.
Second, as I run today not only the Israeli CML patients organization but also the Flute of Light which is the home for blood cancers patients in Israel, I feel it is my responsibility to be at the place where new hopes and optimism are published for patients in different cancers like Lymphomas, CLL, Acute Leukemias and MPN. In addition, ASH is the place to meet with the top management of all the companies we work with and discuss how to strengthen our collaboration for more patients centric activities like patients engagement in clinical trials for example and improved access.
ASH opens every year on Friday with many satellite symposiums sponsored by Pharma on different diseases. This year there was no symposium on CML so I was able to attend the Advocates breakfast organized each year by Pfizer and the ICMLF meeting led by Tim Hughes which included talks on pregnancy in CML by Dragana Milosevic from the Hammersmith, Pediatric CML management by Prof Suttorp from Germany and talks by Dr Benneh from Ghana on CML management challenges in low-income countries.
CML wise the conference included the following sessions: The CML educational session, 3 oral sessions with 6 abstract presentations each, and posters presented at the end of each day at the posters session.
This report will summarize the main topics I found to be interesting at the oral and poster sessions. The main topics were new drugs in CML, TFR and Pregnancy and CML.
If you want to read more info, you can find below each summary the link to the abstract presented.
Food effects on Nilotinib: Presentation of the NIFO Study at ASH 2018
Every medicine has different characteristics how the body converts the tablet or capsule into the active substance that treats the disease. Other medications taken in parallel can influence how much of one or the other drug is being absorbed by the body, which can either increase or decrease the blood levels, impacting efficacy or side-effects. In addition, the TKIs in use with CML have different mechanisms to interact with food taken at the same time as the drug. For example, Imatinib and Bosutinib need to be taken with food, as intake on an empty stomach can cause gastrointestinal irritation. Dasatinib and Ponatinib do not have significant interactions with food, so they can be taken while eating or fasting. Nilotinib and Asciminib need to be taken without food. A poster at this year's ASH provides some interesting new data on Nilotinib.
ASH report on news about generic imatinib
When generic imatinib was introduced between 2013 and 2016 when the Glivec patent expired, generic formulations have been used recently as a more cost-effective treatment, but there are few studies that have prospectively evaluated the efficacy and safety of these drugs. By the time of introduction of generics, many patients and physicians were concerned about whether generic versions of the drug are as effective as the original, but no publications from the more strongly regulated markets have substantiated these concerns.
At this year's ASH congress, two publications addressed the topics of generic imatinib - one observational study from Brazil, Argentina and Italy on first-line treatment with branded and generic imatinib, and one observational study from Italy on switching from Glivec to generic imatinib.
ASH 2018 CML Education Session: With great success comes great responsibility
“June 2018 was the 20th anniversary of the clinical use of the first Tyrosine Kinase Inhibitor (TKI), Imatinib, in CML patients. Since then, the change in prognosis is one of the major success stories of modern cancer medicine”. Having this as an introduction of the CML section in this year’s education book of the ASH reminded me how far we’ve come in the past 20 years. Two decades have passed since first CML patients tested STI571, now called Imatinib, on initiative by CML experts Brian Druker and John Goldman against much resistance of established experts who thought this whole TKI approach is never going to work.
Today, as long as they can access current CML treatments, patients and doctors are no longer concerned with delaying the inevitable progression of the disease or the time towards bone marrow transplant, as it was in 2001. Today’s focus on the best choice of therapy based on the individual molecular biology of the disease, as well as individual comorbidities, side effects, quality of life. The main treatment goals are mainly to reduce disease burden quickly to prevent risk of early progression, and then achieve deep molecular remission and good quality of life. For about one fourth of patients, therapy-free remission after years of treatment is already an attainable goal.
“With great success comes great responsibility” was the motto of this year’s CML Education Session at ASH 2018 – reflecting that with all the choice we have, we must do our best to leverage all therapeutic options to give each patient the best care possible, to live up to the promise that any CML patient can live a normal, long and good life. The three speakers, Prof Jane Apperley from the Hammersmith Hospital in London, Prof Tim Hughes from Adelaide and Prof Charles Craddock from the University of Birmingham made this very practical by outlining therapeutic decision making on two hypothetical cases: 55 year old overweight, smoking Bob with additional chromosomal abnormalities, and 22 year old Sue who was pregnant. The three CML experts touched upon three important areas: choice of first-line treatment, molecular monitoring schedules, and advances in stem cell transplant for patients where TKIs have failed.
[Click on "read more" to read the full article, and click here for the slides of the session.]
ASH 2018 Report (I): Treating CML during pregnancy
The 60th American Society of Haematology Annual Meeting and Exposition is taking place from 1-4 December in San Diego, USA.
The meeting is providing a huge educational experience and the opportunity to review thousands of scientific abstracts highlighting updates in the hottest topics in haematology with the attendance of more than 25,000 health-care professionals as well as many patient advocates.
We are pleased to share with you our first "ASH 2018 Report", contributed by our co-founder Jan Geissler.
