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.
