Tuesday, December 26, 2017

EXCLUSIVE! Blockbuster Data for Lymphoma Patients: An Exhaustive Guide to the Best and Brightest New Treatments


It’s been a very good year for lymphoma patients. At the 59th American Society of Hematology (ASH) Annual Meeting and Exposition in Atlanta earlier this month, an avalanche of mostly positive clinical trial data was presented by pharmaceutical companies for various newly approved treatments for lymphoma, one of the most common cancers in America.
The number of therapies green-lighted this year by the Food and Drug Administration (FDA) for non-Hodgkin’s lymphoma (NHL), specifically, is particularly exciting and encouraging.
But negotiating this whirlwind of new information can be daunting for patients looking for the best treatment options. That’s why I’m here. 
Below, for my fellow lymphoma patients and their loved ones, is a guide in which we take an exclusive, inside look at some of the most significant lymphoma treatments that recently debuted in the market and, hopefully, at your cancer clinic, with the science jargon replaced, whenever possible, with regular English.
For this guide, we talked with patients, physicians and researchers to get the most comprehensive and no-baloney summary for anyone who is about to make a decision about treatment and wants the latest 411 on what works and what doesn’t.
And as if I have to remind anyone, I am not a doctor, I’m just a journalist, patient advocate, and three-time survivor of non-Hodgkin’s lymphoma who’s been writing about this stuff, and living it, since my own diagnosis 21 years ago.
If you have any questions or comments about any of this, please contact me directly at my personal email:  jreno@san.rr.com
Aliqopa

So, let’s start with Aliqopa, a treatment from Bayer Healthcare Pharmaceuticals that’s in a class of drugs known as kinase inhibitors. Aliqopa, which works by blocking several enzymes that promote cell growth, was granted accelerated approval by the FDA in September for adults with relapsed follicular non-Hodgkin’s lymphoma (fNHL).

Follicular is the type of lymphoma I’ve been battling for 21 years. Treatment options for fNHL are limited. The approval of Aliqopa provides an evidently effective new choice for patients who’ve received at least two prior treatments known as “systemic therapies.”

That just means drugs that spread throughout the body to treat cancer cells. They include chemotherapy, hormonal therapy, targeted drugs and immunotherapies. 
From what I’ve been told by lymphoma patients who’ve been treated with Aliqopa, the side effects are often substantially more tolerable than chemotherapy, which will come as good news for those of you who, like me, had a rough time with chemo.
When I was originally diagnosed with cancer, I was treated with a chemotherapy regimen called CHOP. It literally almost killed me. It was brutal. Thankfully not every patient has that experience.
What you should know about Aliqopa is that in a clinical trial of 104 patients with fNHL, this treatment gave 59 percent of patients a complete or partial response for a median 12.2 months.
Lymphoma Patient Embracing New Treatment
Thanks to Aliqopa, Brenda Montgomery got her life back. Brenda, 68, a charming, effervescent woman from Carrollton, Kentucky, was diagnosed with follicular NHL nine years ago. Last July, her doctors told her the cancer had returned. Again.

But she had pretty much run out of options. So, she took an educated risk and entered a clinical trial of Aliqopa after asking her doctors about the clinical trial data. “We didn't know what would happen in the trial,” Brenda tells me, “but after three times in and out of remission, I thought, ‘What have I got to lose’?”

Brenda, who was treated with the drug every three weeks for 18 months, is now in complete remission. The trial was a breeze compared to some of her previous treatments. “It was great, though I did have a few side effects, including soreness in my mouth,” she says.

Brenda, who still works as a Mary Kay representative and loves to have fun with friends at the casinos not far from her Kentucky home, says this drug has enabled her to live her life again. “I have new hope now,” she says. “I’m doing the things I love to do and enjoying my life.”

Gazyva

The newest Non-Hodgkin’s lymphoma treatment to enter the marketplace is Gazyva, an engineered monoclonal antibody from Genentech that targets and attaches to the so-called CD20 proteins found on follicular lymphoma cells as well as some healthy blood cells.

Gazyva, too, represents a new and viable option for follicular NHL patients. It was approved by the FDA just last month for people with previously untreated advanced follicular lymphoma (stage II bulky, III or IV) in combination with the chemotherapy drug Bendamustine, followed by Gazyva alone in patients who responded.

I’m not a big fan of chemo drugs, for reasons I listed above. I tend to support newer protocols that move away from chemo. But that is a very personal choice and I respect others who disagree. There are thankfully plenty of cancer patients who’ve tolerated chemotherapy better than I did.

The trial data shows that a Gazyva-based regimen reduces the risk of disease worsening or death by 28 percent compared to a regimen of Rituxan, the blockbuster monoclonal antibody lymphoma drug also from Genentech/Roche.

Gazyva is designed to attack and destroy targeted B-cells both directly and together with the body's immune system. It is definitely another legitimate treatment option. And it’s interesting that it is in some scenarios positioned to replace Rituxan, which has been the most popular treatment for several types of lymphoma for years.

Lymphoma patients should also be aware that there will soon be more than one so-called “biosimilar” drug designed for lymphoma patients interested in taking Rituxan. Biosimilars are drugs that can be very similar to the drug they are designed to resemble, but there is no way to make them identical. A generic drug, on the other hand, is an exact copy of its reference medicine and must have the same chemical makeup.

Yescarta

Then of course there’s Yescarta, an immunotherapy from Gilead/Kite that is in a new class of cancer treatments called CAR-T that is arguably the most discussed cancer treatment in America at present.

Yescarta, which was approved by the FDA in October, is called an immunotherapy because it uses a patient’s own T-cells to attack cancer cells bearing the molecule called CD19 at their surface. CD19 is expressed in most lymphoma and leukemia cells.

A so-called chimeric antigen receptor T cell (CAR-T) therapy, Yescarta was approved for patients with certain types of large B-cell lymphoma who’ve not responded to or relapsed after at least two other kinds of treatment.

CAR-T has been the subject of an enormous amount of national press. I’ve covered the CAR-T sector for such publications as Yahoo Finance and Healthline, in 2016 and again this year.

Yescarta, the second CAR-T therapy approved by the FDA and the first to be green-lighted for certain types of non-Hodgkin’s lymphoma, is showing very impressive and durable complete remission rates for patients who have exhausted their options.

Survival rates for patients whose large b cell lymphoma recurred were 8 to 10 percent. But with CAR-T the survival rates have increased dramatically: 40 to 50 percent of patients experience a complete response, and show no sign of disease for months and potentially years.

More than 15 months after receiving the treatment, 40 percent of the lymphoma patients who were treated with Yescarta in Kite’s ZUMA-1 clinical trial are in complete remission. And these are patients who for the most part simply have nowhere else to turn.

Kite Pharma, the company that developed Yescarta, was recently purchased by Gilead for just under $12 billion in a purchase that generated global bold-type headlines. That buy should give you some idea of how much the industry, and patients, value this new treatment. It appears to be a game-changer, a remarkable new option that only promises to get better, and safer.

I’m eager to see how Yescarta and other CAR-T treatments will do in the coming years and, eventually, as a first-line therapy. It seems inevitable that the FDA will approve CAR-T as well as other immunotherapies as a patient’s first option, not just a last resort.
Meet the Next Patient to Do Yescarta
Despite how well Yescarta works, shockingly only six lymphoma patients have received the treatment since it was approved two months ago.

As Bloomberg reported, the wait times are creating anxiety in some lymphoma patients. But don’t blame the drug company. Doctors blame the delays on Medicare, the two government health programs, and on the insurance companies.

The sixth Yescarta patient was treated last week, and the seventh will be treated this week at Stanford.

I spoke exclusively with the family of Shazhad Bhat, 52, who has diffuse large B cell lymphoma (DLBCL), and will soon become the seventh patient to receive the treatment.

He and his wife Nicole, who live in Las Vegas with their 12-year-old son, are at preparing for the infusion this week. But this probably would not have happened if not for Nicole’s tireless advocacy for her husband, who works at the MGM and has insurance through his culinary union.

Nicole asked to meet the case member of the insurance plan in person to tell her their situation.“I didn’t have to deal with a red tape fight, I just contacted the case manager and said my husband had been fighting this for almost two years, and asked if I could meet her face to face,” she says.

Nicole asked the case manager one simple question. “I said, ‘Are you going to try to save my husband’s life?’ They said yes. We got it approved. I was not taking no for an answer.”

Nicole says it came down to one person being at the right place at the right time making the right decision. But she says it’s unfortunate that patients are forced to deal with so much governmental red tape and so many reluctant insurance companies.

“This world has become a conglomerate bureaucracy, I come from hotel hospitality and telecommunications, I was a manager for over 20 years. When I see something wrong I just look for ways to fix it,” she says.

Juno’s CAR-T Treatment

Meantime, another leader in the CAR-T sector is Juno Therapeutics, who also brought impressive CAR-T data to the ASH convention.

Juno is developing a CAR-T-based immunotherapy called liso-cel (formerly known as JCAR017), in partnership with Celgene, for adults with diffuse large B-cell lymphoma (DLBCL), the most common form of NHL.

Juno’s trial showed a 50 percent complete response rate, and also impressed observers with its stellar safety numbers. Some lymphoma patients in CAR-T clinical trials have had to contend with something called cytokine release syndrome (CRS), a serious and even potentially fatal toxicity that can result from T-cell cancer therapies.

Cytokines are various proteins that are secreted by certain cells of the immune system and have an effect on other cells. CRS is associated with elevated circulating levels of several cytokines including interleukin (IL)-6 and interferon γ.

But Juno and other pharmaceutical companies in the CAR-T space are working to mitigate the side effects of treatment. Juno, which suffered a tragic death of two patients in a separate clinical trial, has put a priority on patient safety and it appears to have paid off.
The company saw just one of its 67 patients in the B-cell lymphoma trial suffer from severe CRS, whereas Gilead/Kite’s trial for Yescarta saw 13 percent of its patients suffer from severe CRS.

Juno’s Head Researcher Responds

Dr. Sunil Agarwal, Juno’s president of research development, tells me the company is pleased with the 50 percent complete response rate among patients and the strong safety numbers in its trial.

“The 50 percent complete response rate is very exciting for patients in its own right,” Agarwal says. “We are [also] encouraged by the high durable response rate we have seen: greater than 80 percent between 3 and 6 months and greater than 90 percent beyond 6 months.”

Agarwqal is confident that liso-cel’s efficacy and safety profile have a good chance of being the “best in class” as the booming CAR-T sector moves quickly forward. 
  
“We are very encouraged by the emerging safety profile for liso-cel, which challenges the conventional thinking that efficacy inevitably comes with toxicity,” he says. “The clinical data for liso-cel show good efficacy with a tolerability profile that could be beneficial for patients and allow for outpatient administration. This would also be beneficial for hospitals and payers.”

Eureka: An Even Newer Idea, But Will It Work?

On that patient safety note, there is an even newer company in the T cell immunotherapy space whose treatment potentially harnesses the body’s T cells to attack lymphoma but removes the risk of cytokine release syndrome.

Eureka Technologies, a small but up-and-coming biotech firm, recently announced the FDA’s allowance of a Phase I clinical trial for ET190L1-ARTEMIS T cells in relapsed and refractory CD19-positive NHL.

Eureka expects to enroll the first patient in this trial in the first quarter of 2018. In pre-clinical studies, Eureka’s T-cell technology matched the cancer killing potency of current CAR-T therapies, but with a dramatic reduction in the levels of inflammatory cytokines released.

In addition, these studies have shown that ET190L1-ARTEMIS T cells are less exhausted and more naive and therefore expected to have improved persistence.
If confirmed in the clinic, this could result in a longer-term therapeutic benefit to patients and of course pose serious competition with the other CAR-T makers.
“We designed our ARTEMIS T cell receptor platform with the goal of improving upon the efficacy and safety of current T cell therapies,” Dr. Cheng Liu, President and Chief Executive Officer of Eureka Therapeutics, says in a statement. 
The principal investigator for the Phase I clinical trial is Dr. David Rizzieri, professor of medicine, a leading blood cancer physicians and researcher at Duke Cancer Institute at Duke University School of Medicine, says in a statement that he is “excited to work with Eureka Therapeutics in bringing this innovative therapeutic approach to the clinic.
Rizzieri says this treatment has the potential to “reduce the serious side effects that I have seen in patients being treated with current approaches.”
The CAR-T Sector Continues to Grow

Johnson & Johnson also just announced it is paying $350 million through its subsidiary, Janssen Biotech Inc., to collaborate on a new CAR-T treatment for myeloma with a little-known Chinese company called Legend Biotech. 

Under the licensing deal announced Thursday, Janssen and Legend will equally split development costs and any future profits of the CAR-T candidate in multiple myeloma — excepting Greater China, where the Legend will take a 70% share.

It remains to be seen if Johnson & Johnson will pursue any CAR-T treatments for lymphoma, in China or elsewhere. But it certainly seems possible, given the fact that its subsidiary, Jannsen, is already bringing a lymphoma treatment to China.

As I reported in Healthline, Janssen and Pharmacyclic, an AbbVie company, are brining ibrutinib, which treats several types of lymphoma and leukemia, to China.

Ibrutinib is an oral therapy that inhibits the function of Bruton’s tyrosine kinase (BTK), a target for therapy of B cell diseases that includes several types of lymphoma as well as chronic lymphocytic leukemia.
Cancer Genetics

Another company that lymphoma patients may not know about yet, but which is doing some of the most advanced and significant work in the entire cancer field, is Cancer Genetics (CGI).

The company, whose latest data presented at the ASH convention generated widespread interest, is at the forefront of precision medicine, which is the effort to increase the efficacy of a treatment and speed up the process of finding the right treatment or treatments for patients.

CGI provides molecular and biomarker tests that enable physicians to personalize patient management. The company’s technology enables pharmaceutical companies involved in clinical trials to reduce adverse drug reactions in patients with lymphoma, and other cancers, by providing information regarding genomic factors influencing patient responses to treatments.

In an exclusive interview, Dr. Rita Shaknovich, CGI‘s new chief medical officer and group medical director, said the company is looking at the genetics of cancer, and adapting its findings to choose the best possible treatment options for the patient.

Shaknovich’s esteemed research, which has been funded by such agencies as National Institute of Health (NIH), Leukemia and Lymphoma Society (LLS) and Lymphoma Research Foundation (LRF), has focused largely on lymphoma and its genetic mechanisms.

Her work for the last decade-plus has identified some of the genetics involved in the conversion of a tissue with a normal growth patter into a malignant tumor.

“Technology has improved. We know there are dominant mutations in certain types of disease, and we are gaining a better understanding of the genomic events that lead to transformation of normal cells into lymphoma,” she says. “A large number of cases have been sequenced; we know there are certain genomic abnormalities.”

Shaknovic says CGI tries to assess biomarker expression in B cell lymphoma, and that data hopefully will enable the design of clinical trials using inhibitor treatments.  

“The good news is there are companies focusing on creating drugs that target those abnormalities. This is what precision medicine is all about,” she says.

At ASH this month, CGI announced the results of a study demonstrating the potential value of its precision medicine technology in better understanding diffuse large B cell lymphoma (DLBCL).

In a statement, Panna Sharma, president and CEO of CGI, says
the study demonstrates that choice and integration of diagnostic modalities can provide “key additional information to assist oncologists to more accurately select therapeutic options for their patients.”

While not a household name, yet, CGI appears well-positioned, with much study of NHL already in the books, to have a profound effect on lymphoma patient management treatments.

It’s pretty evident to me that CGI’s technology will save lymphoma patients’ lives in the very near future, if it hasn’t already. 

Sunday, November 19, 2017

San Diego State's Rashaad Penny: The Best College Football Player In America In 2017


A few weeks ago, I wrote here that any sportswriter or other member of the Heisman Trophy voting committee that doesn’t select San Diego State University running back Rashaad Penny as a finalist for the prestigious award for college football's best player should have his or her voting priveledges taken away. 

But after watching last night's game, in which Penny finished with an astounding 429 all-purpose yards, allow me to amend that declaration a bit: Those of you who don't vote for Penny as a Heisman finalist should never be allowed to write about college football again!

Penny is easily one of the best three college football players in the nation in 2017. He deserves to be a Heisman finalist. If you've watched him play this year, you surely agree. It's indisputable at this point. 

San Diego State beat Nevada last night 42-23 in a game that will only confirm and expand the Aztecs’ postseason options. This will mark the eighth bowl game in the last eight years for San Diego State football. But the bigger story last night was the historic performance from Penny, who leads the nation in rushing and all-purpose yards. 

It was a game for the ages for Penny, who ran for 222 yards to bring his total to 1,824, putting him atop the nation's running backs. Stanford’s Bryce Love, a surefire Heisman finalist who Penny outplayed in San Diego State's win over #19 Stanford in September, is in second place with 1,723 yards.

In addition to running for 222 yards last night, Penny also returned a punt 70 yards for a touchdown (it was the first punt return of his college career). Not long after that, Penny returned a kickoff 100 yards for another touchdown. The kickoff return for a TD is the seventh of his career, tying the college record. He had four touchdowns total. 

Nevada played well and was shooting for the upset, but Penny sealed the game for San Diego State. His 429 all-purpose yards broke the school record of 422 set 26 years ago by Marshall Faulk during his monster 386-yard rushing game against Pacific. 

I was at that game back in 1991. It was the greatest performance by a running back I'd ever seen in college football. Until last night.

Sports Illustrated college football writer Bruce Feldman wrote yesterday that the top five Heisman candidates in his book are Oklahoma quarterback Baker Mayfield, and four running backs: Stanford's Bryce Love, Penn State's Saquon Barkley, Wisconsin's Jonathan Taylor, and Auburn's Kerryon Johnson. 

Now Bruce, before you crack your knuckles and start typing me defensive reasons why I'm wrong and why Penny doesn't deserve to be a Heisman finalist, save it. The only argument you can really come back with when a player who isn't in a Power Five conference has these kind of historic numbers is that he hasn't done this against any legit competition.

But Penny demonstrably outplayed Bryce, who is your #2 candidate on the Heisman list, when San Diego State beat Stanford. Penny finished that game with 206 total yards on offense vs. Love’s 187 yards. Both are great athletes. Penny's just a little better.

Penny also had a remarkable game against Arizona State, another Power Five team that beat #5 Washington and #24 Oregon and is headed for a bowl game this year. Against the Sun Devils, in Tempe, Penny had 353 all-purpose yards, including 216 rushing on just 18 carries, 38 yards receiving and 99 yards on special teams.

The opponent does not matter. Penny dominates all comers. There is simply no sound argument left for Bruce or anyone else to justify leaving him on the outside looking in to the Heisman ceremony in New York City next month. 

Don't let this happen yet again, Heisman voters. You slighted Faulk, the college and NFL hall-of-famer who was easily the best football player in the nation when you gave the trophy instead to Gino Torreta, who quarterbacked a great Miami team but was in no way, shape or form a better football player than Faulk was that year or any year. 

You did it again last year to Donnell Pumphrey, the unstoppable and unbelievable San Diego State mighty might who broke the all-time college football rushing record last season and ran for more than 2,000 yards. He deserved to be a Heisman finalist, too.

But this time y'all are out of even bad excuses. Those of you who didn't vote for Pumphrey embarrassed yourselves, but if you make the even bigger blunder and leave Penny out, you will leave your credibility left hanging by a thread from your wrinkled Dockers.

If I sound pissed... bingo! Enough is enough is enough. I have great respect for sportswriters, generally, and often defend them when I'm in the company of those who have no clue how tough the gig really is. But when it comes to the Heisman vote, sportswriters, and especially ESPN analysts, have been displaying a regrettable amount of ignorance and bias for far too long.

Notice I’m not even saying Penny deserves to win the dang thing. He does, of course. I called him the best player in college football above because he is the best player in college football. But all I am saying here is that he deserves to be part of this ceremony. The Heisman finalists are supposed to include the best individual football players in the country. Penny is one of those. 

Some years, Heisman voters make a reasonable argument when Division One players have amazing stats but haven't played against strong competition. But I will say it one more time: two of Penny’s finest games this season were against Power Five teams. He's great no matter who he is playing.
Heisman voters, please stop shaming the award with your myopic, clueless votes.