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Will this happen in the treatment of multiple myeloma?

by Cheryl G on Sat Mar 26, 2016 6:46 pm

There is an interesting discussion going on in another part of the medical community that deals with blood cancers -- in particular, chronic myeloid leukemia (CML). I think that Mark here in the forum has mentioned this subject before, but it didn't really sink in until I saw a new article in the journal Blood.

The article is by a couple of physicians in Australia. They point to the impact new treatments like Gleevec, in the "tyrosine kinase inhibitor" class of drugs, are having on patients with CML. With these treatments, some patients are achieving remissions that are so deep that they don't have to be treated anymore because there is only a very low chance that they will relapse.

Outside the medical world, people would just say that these patients have been cured.

Wouldn't that be a wonderful thing to have happen in multiple myeloma? :)

I haven't read the article. You have to be a subscriber or pay to read it. Still, if you just read the abstract slowly and let yourself digest it, you will recognize what a significant thing it is that the authors are discussing.

Here's the abstract, broken up a little bit to make it more readable:

"The dramatic success of tyrosine kinase inhibitors (TKIs) has led to the widespread perception that chronic myeloid leukemia (CML) has become another chronic disease, where lifelong commitment to pharmacological control is the paradigm. Recent trials demonstrate that some CML patients who have achieved stable deep molecular response can safely cease their therapy without relapsing (treatment free remission; TFR). Furthermore, those who are unsuccessful in their cessation attempt can safely re-establish remission after restarting their TKI therapy.

Based on the accumulated data on TFR we propose that it is now time to change our approach for the many CML patients who have achieved a stable deep molecular response on long-term TKI therapy. Perhaps half of these patients could successfully achieve TFR if offered the opportunity. For many of these patients ongoing therapy is impairing quality of life and imposing a heavy financial burden while arguably achieving nothing. This recommendation is based on the evident safety of cessation attempts and TFR in the clinical trial setting.

We acknowledge that there are potential risks associated with cessation attempts in wider clinical practice, but this should not deter us. Instead we need to establish criteria for safe and appropriate TKI cessation. Clinical trials will enable us to define the best strategies to achieve TFR, but clinicians need guidance today about how to approach this issue with their patients. We outline circumstances in which it would be in the patient's best interest to continue TKI, as well as criteria for a safe TFR attempt."


Here's the reference:

TP Hughes & DM Ross, "Moving treatment-free remission into mainstream clinical practice in CML", Blood, March 24, 2016 (abstract)

Cheryl G

Re: Will this happen in the treatment of multiple myeloma?

by dogmom on Sun Mar 27, 2016 5:25 am

Wow, maybe myeloma can benefit from this as well?

dogmom
Who do you know with myeloma?: husband
When were you/they diagnosed?: December 2015
Age at diagnosis: 58

Re: Will this happen in the treatment of multiple myeloma?

by KarenaD on Sun Mar 27, 2016 10:43 am

Hi Cheryl,

Thank you for posting this very interesting article. I become so hopeful when I see the strides being made in CML research and treatment. We all dream about TFR (treatment free remission), and I pray that dream is close to reality for all multiple myeloma sufferers very soon.

There also seems to be some early research ongoing in TKIs for the treatment of multiple myeloma. I found this study on sorafenib (Nexavar) vs. multiple myleoma, and while I find most of the abstract difficult to follow, the conclusion is clear:

"In summary, our study provides compelling evidence for the future evaluation of the multi-TKI sorafenib as a new therapeutic strategy for the treatment of multiple myeloma in the clinic.”

Source:

P Kharaziha et al, "Sorafenib Has Potent Antitumor Activity against Multiple Myeloma In Vitro, Ex Vivo, and In Vivo in the 5T33MM Mouse Model", Cancer Research, October 15, 2012 (full text of article)

KarenaD
Name: Karen
Who do you know with myeloma?: Myself
When were you/they diagnosed?: November 4, 2015
Age at diagnosis: 54

Re: Will this happen in the treatment of multiple myeloma?

by Mark11 on Mon Mar 28, 2016 3:13 pm

Thanks for this post, CherylG.

The posters here are very informed about myeloma therapy, but there are times that I think they could learn a lot by seeing how much more effective therapies are available for other blood cancers. Here is a study on 190 patients with limited stage diffuse large B-cell lymphoma I saw that showed the five year statistics for patients that did 6 cycles of R-CHOP and no maintenance.

"The responses to therapy were 180 complete responses, eight PR, and two pro­gression of disease (PD). The 5-year progression-free survival and 5-year overall survival rates were 84% and 90%, respectively, both in plateau. During the observation period, 29 patients experienced PD."

Source: N Tomita et al, "R-CHOP therapy alone in limited stage diffuse large B-cell lymphoma," British Journal of Haematology, Feb 2013 (full text of article)


It seems like we are a LONG way away from having these types of outcomes in myeloma. The proteasome inhibitor / IMID / dex combo does not appear to be all that effective when you see what R-CHOP can do for some types of lymphoma.

The cynical part of me finds it interesting that therapy breaks for CML patients that respond to Gleevec / TKI's are now being discussed now that Gleevec is coming off patent. The other reason this is significant is that the therapies that currently are considered cures for blood cancer are not considered "targeted" therapies. Currently therapies that are considered cures are things like R-CHOP for certain types of lymphoma and allo transplant in CR1. As far as I am aware, this would be the first example of an approved, targeted therapy alone being considered a potential cure for a blood cancer.

"For many of these patients ongoing therapy is impairing quality of life and imposing a heavy financial burden while arguably achieving nothing."

Fortunately I have been myeloma therapy free for 5 years, but the reduced quality of life (QOL) from continuous therapy is something I have been discussing here for a while with respect to myeloma patients. Note I put up a couple of QOL studies for long term survivors taking Gleevec in the quality-of-life thread here in the forum.

Mark11

Re: Will this happen in the treatment of multiple myeloma?

by Cheryl G on Mon Mar 28, 2016 8:43 pm

Hi Mark,

You made an interesting point when you wrote:
The cynical part of me finds it interesting that therapy breaks for CML patients that respond to Gleevec / TKI's are now being discussed now that Gleevec is coming off patent.

I hadn't thought about that.

I am the first to admit that I know only a little about what is going on in the treatment of other blood cancers. That is why it is helpful to read what you post here in the forum about such developments. (I will also admit that I learn the most from your postings where you explain things in your own words in addition to providing references and abstracts.)

Cheryl G

Re: Will this happen in the treatment of multiple myeloma?

by Mark11 on Wed Mar 30, 2016 12:55 pm

Hi CherylG.,

The patients I know and keep in contact with are acute leukemia patients since I met them while doing the transplant and I meet them at survivor events at the transplant center. As I mentioned previously, my original treatment plan was to do Velcade / Doxil / Dex to CR and than do an allo transplant as soon as I got to CR. Acute leukemia patients have the same treatment plan I used, they just use different drugs. I can relate to them a lot more than I can relate to most myeloma patients.

I always like to show the results of R-CHOP because it shows how effective newer therapies can be when combined with older therapies. CHOP has an alkylator and an anthracycline, Many myeloma patients try to avoid those. I am not sure why patients would want to avoid therapies that have helped cure blood cancer patients, but they are not new so patients try to avoid them.

The other issue that should be interesting to watch with regard to Gleevec when it comes off patent is to see if Medicare / Insurance Co.'s in the US will only pay for the generic version of Gleevec since it will be much cheaper than the second generation TKI's that are still on patent. Currently it is physicians choice since the prices and effectiveness are roughly the same.

Right on que since we were discussing Gleevec, there were a couple of abstracts that I thought were interesting that just came up on PubMed. The full articles are not available without paying, but the abstracts are interesting. Note it seems the second generation TKIs have more long-term side effects than Gleevec. I would also point out while it sounds great to be able to take a pill and make a disease chronic, the reality seems to be quite different for the patients actually doing it. I would much rather have access to an aggressive therapy like R-CHOP that would lead to a long /permanent treatment free interval than need to keep taking a drug to stay in remission.

Abstract #1:

"Most patients with chronic myeloid leukemia have deep and durable responses when treated with BCR-ABL1 tyrosine kinase inhibitors (TKIs). Imatinib (the first approved TKI), nilotinib, and dasatinib are used in newly diagnosed, relapsed or intolerant patients, while bosutinib and ponatinib are used only in relapsed or intolerant patients. Previously the drug of choice was related to the likelihood of response and, to a small extent, patient comorbidities. The long-term toxicities, particularly cardiopulmonary side effects, are now impacting treatment choice, making patient comorbidities of significant concern. About 10 % of patients do not tolerate their initial BCR-ABL1 TKI and an increasing number are developing long-term side effects, particularly with the second generation drugs. Side effects of the five drugs reviewed here highlight the differences between cardiovascular, pulmonary, gastrointestinal, and endocrine toxicities, as well as possible second malignancies. There is increasing evidence that patients whose disease is controlled by TKI's will have greater impact on their quality of life from comorbidities or drug adverse events than from the disease itself."

Source: L Caldemeyer et al., "Long-Term Side Effects of Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia," Current Hematologic Malignancy Reports, April 2016 (abstract)


Abstract #2:

"Since the development of imatinib and other tyrosine kinase inhibitors (TKIs), the prognosis for patients with chronic myeloid leukemia (CML) has markedly improved, such that most patients diagnosed with CML can now expect to live with their disease rather than die from it. However, most patients will require long-term treatment, which has deleterious effects on health-related quality of life. We review recent literature on drug-related adverse effects, long-term medication adherence, limitations to fertility and pregnancy, effects on cognitive function, ability to work, financial toxicity, pediatric populations, and treatment discontinuation. While patients with CML are fortunate to have excellent therapies available to control their disease, many are unable to lead normal lives, which challenges the notion that research is no longer needed in CML. Curing CML, i.e., no detectable disease and no need for daily medications, should remain the ultimate goal."

Source: KE Flynn et al., "Quality of Life and Long-Term Therapy in Patients with Chronic Myeloid Leukemia," Current Hematologic Malignancy Reports, April 2016 (abstract)


Mark

Mark11


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