Tuesday, June 30, 2015

Renewed Hope

I want to make you all aware of a project called Esperanza Renovada (Spanish for "Renewed Hope"). Esperanza Renovada is a non-profit project designed to support cancer patients, created by a Follicular Lymphoma patient named Kathy and her husband and caregiver Dennis.

After Kathy was diagnosed with Follicular Lymphoma, she went through a clinical trial for Rituxan, and did great. As we all know, FL is as much an emotional disease as a physical one, and at the end of her treatment, Kathy and Dennis went to Puerto Rico for some relaxation. That trip worked on her emotional healing as well as the Rituxan worked on her physical healing.

Eventually, Kathy and Dennis bought some land in Puerto Rico and built a cabin, and then decided to share that emotional healing with other cancer patients.

And that's what Esperanza Renovada is all about. Their cabin is currently rentable, and they are working on building a lodge with more cabins. The money that comes in from the cabin rentals will go toward funding lodging for cancer survivors, who will be able to stay at Esperanza Renovada for free. As the web site puts it, "This is a time when many survivors need a place outside of a clinical environment to get away and discover their new life's focus and reconnect with family members."

If you want to learn more about Esperanza Renovada, you can visit the website at the link above.  You can also hear Kathy and Dennis talk about the project on The Morning Show, a radio show on WRCO in Wisconsin. Click here, and scroll down to "Restorative Escape."

Kathy and Dennis are still looking for donations, and you can support them directly from their website. You can also support them by renting their cabin, if you are planning a trip to Puerto Rico. You can find out more about that on the website, too.

I have written a lot about how important an online support group was for me, especially in the early days of my diagnosis. I learned a lot about Follicular Lymphoma, and I got a lot of hope from some special people -- strangers who I had never met in person, but who showed a lot of caring for me. Kathy was one of those special people. I haven't talked to her about Esperanza Renovada, but I know how much it means to her to be able to help other cancer patients, since I was one that she helped.

You look like you need a vacation. Maybe Puerto Rico......?

Sunday, June 28, 2015

Dr. John Leonard on R-Squared

Before I get to  Lymphoma stuff, I need to comment on this first:

The clothing store Old Navy has an online catalog, and they divide the clothes into the usual categories: men, women, children; pants, shirts, shoes; whatever. But then they divide things into certain "styles," too, and I have an objection to one: the "blogger" style.

You can see a sample here of what kind of clothes they think bloggers wear. I think the slip-on canvas shoes actually look kind of comfortable (though they do remind me a lot of the espadrilles my mother wore in the 70's). But I want to make it very, very clear right now: I will never, ever, wear a straw fedora. Also, there is way too much "skinny" clothing in this collection. Honestly, I don't know too many skinny bloggers. We actually tend to sit around quite a bit. It's not a lifestyle that results in "skinny" anything, except maybe "skinny lattes" when we're fooling ourselves that they are healthier.

Apparently, "comfort" is the goal.

(Though, that doesn't explain the fedora.....)

**********************************

On to Lymphoma stuff:

The Lymphoma Program at NewYork-Presbyterian Hospital/Weill Cornell Medical College publishes a blog (no word on whether their blogger wears canvas slip-on shoes) called "New Developments in Lymphoma." I've linked to them before, though it's been a while.

Their most recent post is pretty interesting:

Dr. John Leonard, who teaches at the Cornell Medical College, gives a brief overview of recent studies of Lenalidomide + Rituxan, also known as R-Squared (Lenalidomide = Revlimid).

He discusses the AUGMENT trial that was reported on at ASCO, and mentions a couple of other trials that have moved onto phase III (I think these were the "promising" ones I wrote about a few weeks ago.

You can see the video here. It's pretty short, and doesn't have time to get into much detail, but if nothing else, it's a good excuse to mention the Cornell blog again, and to encourage you to read  around in it.

(And, of course, a good excuse to reconsider my wardrobe.)


http://cornell-lymphoma.com/2015/06/26/dr-john-leonard-discusses-use-of-lenalidomide-rituximab-in-patients-with-recurrent-follicular-lymphoma/

Thursday, June 25, 2015

Nivolumab

I've been seeing a lot of reports from the International Conference on Malignant Lymphoma in Lugano, Switzerland. There wasn't much on Follicular Lymphoma from this year's ASCO conference. Chicago is a wonderful city, and I've enjoyed myself the few times I've been there. But if some Lymphoma researcher had to choice to go to Switzerland instead? Yeah, that's where I'd go, too. (Spent a day in Zurich once, many years ago. It was gorgeous. I got a ticket for not wearing my seatbelt while driving in the Swiss Alps. I'd still take Lugano over Chicago.)

Anyway, it looks like there has been some good stuff being presented over there. One presentation involved a small phase I trial for Nivolumab, a monoclonal antibody that targets PD-1.
International Conference on Malignant Lymphoma in Lugano, Switzerland.
- See more at: http://www.onclive.com/conference-coverage/ICML-2015/Nivolumab-Elicits-Durable-Responses-in-Lymphoma#sthash.zUdO31OE.dpuf


PD-1 has been getting a lot of attention in the last couple of years, and it is seen as a potentially excellent target for treatments. PD-1 stands for "Programmed Death." Normal cells have a kind of expiration date built in to them; cancer cells find ways to block that expiration date, so they keep on living even after they were supposed to die. One way this happens is when a ligand called PD-L1 attaches to the PD-1 (the L in PD-L1 stands for "Ligand," which is a substance that attaches to something else -- that's a big oversimplification).

So PD-1 (good) gets blocked by PD-L1 (bad), so we need something to block that. And that's where Nivolumab (good) comes in. Nivolumab allows PD-1 to do its job, and let the cells die the way they are supposed to. No runaway cells means no cancer.

The trial involved 104 "heavily pre-treated" patients with a bunch of different types of blood cancers. Of those 104, 31 had some kind of B-Cell Lymphoma. I can't tell how many of those had Follicular Lymphoma, but the results for that group look pretty good:  The Overall Response Rate was 75%, and after 82 weeks (about a year and a half), most of those patients had still not had the FL return.

Nivolumab seems pretty effective in a whole bunch of cancers, not just the liquid kind that we are all familiar with. It will be interesting to see if, in a few years, we see some trials involving Nivolumab in combination with something like Rituxan or another targeted treatment that seems more geared toward Lymphoma, specifically.

The usual warning applies here -- this is a phase I trial, so there's a long way to go before you see this in the treatment room. But it does show that, once again, targeted therapies seem to be where we are headed.


In those with follicular lymphoma, the ORR was 75% with a duration ranging from 27 to greater than 82 weeks. Most responses remained ongoing at the time of the analysis. - See more at: http://www.onclive.com/conference-coverage/ICML-2015/Nivolumab-Elicits-Durable-Responses-in-Lymphoma#sthash.zUdO31OE.dpuf

Friday, June 19, 2015

Temsirolimus for Follicular Lymphoma

The journal Cancer has published an early preview of an article called "A Phase 2 study of Weekly Temsirolimus and Bortezomib for Relapsed or Refractory B-cell Non-Hodgkin Lymphoma: A Wisconsin Oncology Network Study." 

The study involved Temsirolimus, also known as Torisel, and Bortezomib, also known as Velcade.  The two treatments are both in the general category of "inhibitors," meaning they keep something from happening -- something that cancer cells need to happen.

We already know about Bortezomib/Velcade. It's been around for a while, and is approved for use with a couple of other blood cancers, and has been in some trials for Follicular Lymphoma. It is a proteasome inhibitor, meaning it keep proteasomes from working. Proteasomes' job is to break down proteins in the cell when they are no longer needed -- kind of like taking out the garbage. When they stop working, the proteins don't get broken down. Instead, they pile up and basically kill the cell from the inside.

I don't know much about Temsirolimus. It has been around for about as long as Velcade has, but it is usually used on renal cell carcinoma, a cancer of the kidneys. It is another type of inhibitor, a Rapamycin Inhibitor, sometimes called a mammilian target of rapamycin (or mTOR) inhibitor. Like other inhbitors, Temsirolimus messes with the processes that cancer cells need to happen in order to survive. In this case, Temsirolimus messes with mTOR, which seems to be an important target, since it controls a lot of other processes inside the cell that determine its survival. If the enzyme is blocked by Temsirolimus, important stuff doesn't happen, and the cell can't grow and survive.

So these two different treatments, Temsirolimus and Bortezomib/Velcade, block different things that are both important to the cell. Combining them seems like a smart strategy -- a double attack on the cancer cells, coming from two different directions.

The phase 2 study described in the article involved 39 patients with different types of B-cell NHL, including Follicular Lymphoma. All 39 patients were heavily pre-treated -- they had already received different treatments, which either stopped working or didn't work in the first place. Of the 39 patients, 3 had a Complete Responses and 9 had a partial Response.

Overall, the patients had a median Progression-Free Survival of 4.9 months. However, the median PFS for the 9 patients with Follicular Lymphoma was 16.5 months, more than three times the median for the entire study.

The authors of the study believe the results justify further study of this combination for patients with  different types of NHL, especially Follicular Lymphoma.

There is certainly some cause for hope here, though it is important to remember that this is a very small study, especially the number of Follicular Lymphoma patients (just 9). What does give me reason for hope, though, is that we have more data here for the effectiveness of inhibitors in general. This type of treatment seems like it will play a big part in our near-term futures as Follicular Lymphoma patients, and the more we can learn about them, the better off we will be in figuring out which ones work on FL, which work best together, and which combinations might make sense to try in the future.

Sunday, June 14, 2015

ASCO: Idelalisib for Follicular Lymphoma

Closing out the review of ASCO with a look at a report of a phase II clinical trial for Idelalisib, the PI3Kδ inhibitor.

Idelalisib is also known as GS-1101 or CAL-101, and its job is to inhibit, or stop an enyzme that controls functions like cell growth, survival, and reproduction in cancer cells. Blocking that enzyme means stopping the cancer.


The clinical trial focused on Follicular Lymphoma patients who are heavily pre-treated, refractory to R+chemo (that is, Rituxan and chemotherapy have stopped working), specifically an alkylating agent, like what a patient would get in CHOP or Bendamustine. Basically, the trial looks at FL patients who have used up most of their options.

72 patients were involved in the trial. The results were great -- 57% of them saw their lymph nodes reduced in size by at least half.The Overall Response Rate was 56% (10 Complete Responses and 30 Partial Responses). The median response duration was 11 months overall, and 27 months for patients that had a Complete Response. Progression-free survival was 11 months, which doen't seem like a lot, but was "substantially longer" that the last treatment the patients had received (remember, this is a group that had pretty much run out of options).

So this is great news for us. A very specific arrow for a very specific quiver.  And, bigger picture -- it gives us an even better sense that kinase inhibitors, and other, newer targeted therapies, are working as well as we had hoped.

So, closing things out, ASCO wasn't about quantity for Follicular Lymphoma, but definitely about quality. I mentioned the study on Polatuzumab Vedotin in my post on Dr. Bruce Cheson's ASCO Preview, and the more I read about it, the more interesting it seems. And the R-Squared trials now underway look great, too.

Lots to keep an eye on for the future.

Monday, June 8, 2015

ASCO: The Future of Revlimid for Follicular Lymphoma

More from ASCO (even though it was over a week ago):

Revlimid (also known as Lenalidomide) made a few appearances at ASCO, though they didn't necessarily present anything that will make a difference at your n ext oncologist appointment. Let's say they said a lot about the future of Revlimid/Lenalidomide for Follicular Lymphoma.

The first presents results from a Phase I clinical trial that focused on dosing -- trying to figure out how much to give to patients. The paper is called "Bendamustine and rituximab and lenalidomide (BRR) in the treatment of relapsed and refractory low grade non-Hodgkin lymphoma (NHL): Final results of phase 1 study NCCTG N1088/ALLIANCE."

As the title suggests, this looks at what happens when researchers give Bendamustine to the "R-Squared" (Revlimid + Rituxan) regiment. It's a pahse I study, so it's small, and its purpose is to figure out how much to give, so there isn't an expectation of great results.

That said, they got great results anyway. They involved 15 patients, 6 of whom have Follicular Lymphomna, and gave them different doses of Bendamustine and Revlimid, and the same standard dose of Rituxan. The study had a 100% response rate -- 9 Partial Responses and 6 Complete Responses. And on top of that, they determined the most effective dosage for the three agents. This shows some great hope for the future.


Two other sessions described phase III clinical trials that have already started enrolling.

The first is the MAGNIFY Trial. (I want a job coming up with names for clinical trials). This one focuses on Maintenance. They hope to enroll 500 patients with indolent lymphomas (including Follicular Lymphoma). All will be given R-Squared (Revlimid + Rituxan) as an initial treatment (none will have received any other treatment). Then half will be given Rituxan Maintenance (every 2 months), and the other half will get R-Squared Maintenance (again, every two months). It will be interesting to see if this alternate way of providing Maintenance proves to be an effective alternative to Rituxan Maintenance. I'm especially interested in what kind of side effects will come from taking Revlimid for that long.

The second trial described at ASCO is the AUGMENT Trial. This one is also a phase III trial, and will also involve several types of indolent lymphoma, including FL. For this one, though, patients have already received some kind of initial treatment, and are Relapsed or Refractory (that is, the disease has come back, or never fully left). This study will involve a direct comparison between Rituxan and R-Squared. Half of the patients will get R-Squared, and the other half will get Rituxan + a placebo. Again, this kind of direct comparison to Rituxan will tell us a lot about whether we have a viable alternative to this common treatment.

So, not much to report from ASCO about how great R-Squared is, but there is lots of reason for excitement about the future.

Still a few more goodies from ASCO to talk about. I'll get to them soon.


Wednesday, June 3, 2015

ASCO: Choosing Treatments for Follicular Lymphoma

Another quick ASCO review:

AJMC has a report of a session from ASCO called "Incorporating Novel Agents into Lymphoma Therapy: Value in Everyday Practice." The session included several doctors who discussed their experience with some newer treatments.

Discussing Follicular Lymphoma was Dr. Gilles Salles of Lyon, France. As reported in the AJMC article, Dr. Salles had a few things to say about some newer FL tratments:

  • Attempts to improve on Rituxan, by developing other monoclonal antibodies that target CD20, have been disappointing. Ofatumumab isn't as effective, and Obinutuzumab performs about as well (but not better).
  • Some other monoclonal antibodies are in the works. They target different proteins that Rituxan targets: CD22, CD37, CD74, and CD80. We're still waiting to see if they improve in Rituxan. [This is just a reminder to us all about how amazing Rituxan is, and how much it has changed things for FL patients.]
  • Lenalidomide (also known as Revlimid) has been useful in helping the immune system recognize that FL cells don't belong there. [I hope to write more on Revlimid at ASCO very soon.]
  • Anti-PD1 treatments are still getting the cancer research community excited. One of them, Pidilizumab, when combined with Rituxan, resulted in more than 50% of Follicular Lymphoma patients having a response.
  • Pathway targeting treatments are also very promising. Idilalisib showed promise in a phase 2 study being presented at ASCO, with a 56% response rate.
Dr. Salles cautioned against using some of these newer agents as first-line treatments for patients with low tumor burden. While they are more targeted than traditional chemotherapy, they still carry some side effects, and at this point, they cost a lot. He thinks other, older treatments (like Rituxan, I assume) can keep things under control while helping maintain a good quality of life in the patient.
Incorporating Novel Agents into Lymphoma Therapy: Value in Everyday Practice.” - See more at: http://www.ajmc.com/conferences/ASCO2015/Choosing-Ideal-Lymphoma-Regimens-in-the-Clinic#sthash.ZRjsAFW1.dpuf
Incorporating Novel Agents into Lymphoma Therapy: Value in Everyday Practice - See more at: http://www.ajmc.com/conferences/ASCO2015/Choosing-Ideal-Lymphoma-Regimens-in-the-Clinic#sthash.ZRjsAFW1.dpuf
Incorporating Novel Agents into Lymphoma Therapy: Value in Everyday Practice - See more at: http://www.ajmc.com/conferences/ASCO2015/Choosing-Ideal-Lymphoma-Regimens-in-the-Clinic#sthash.ZRjsAFW1.dpuf


Interestingly, he mentioned Stem Cell Transplants as options for younger patients who relapse, while older patients might consider some non-chemo treatments.


It's a nice summary of where we are, from a well-known expert in Follicular Lymphoma.