FDA
Approves Novel Car T-Immunotherapy For The Treatment Of Multiple Myeloma
By Lee Greenberger, PhD, Chief Scientific Officer at LLS
| March, 2021
Chimeric Antigen Receptor (CAR) T cell-therapy is on a roll. Today
marks the seventh approval of CAR T therapy since the first approval in 2017.
While all prior approvals with CAR T have directed the engineered T-cells to
CD19, a marker on the surface of malignancies derived from B-cells, this is the
first approval of a B-cell maturation antigen (BCMA)-directed CAR T.
Idecabtegene vicleucel or ide-cel (Abecma) is the first approval of a CAR
T for multiple myeloma. This approval comes on the heels of two new indications
for CD19-directed CAR T: axicabtagene ciloleucel (Yescarta®) to treat resistant
forms of indolent non-Hodgkin lymphoma, as well as the first approval of new
CD19-directed CAR T, lisocabtagene maraleucel (Breyanzi®), for resistant forms
of aggressive non-Hodgkin lymphoma.
LLS takes special pride in FDA approvals for CAR T therapies. Our
initial investment in CAR T in the 1990’s, when CAR T, and indeed immunotherapy
to treat cancer was in its infancy, has turned into a game-changing therapeutic
giving new hope to patients with limited treatment options and often very poor
prognoses. Through LLS academic grants and our Therapy Acceleration Program®
(TAP) investment in biotechnology companies of over $50M in the past 30 years,
LLS has been instrumental in bringing four CAR T-therapies to patients:
axicabtagene ciloleucel (Yescarta®), tisagenlecleucel (Kymriah®),
brexucabtagene autoleucel (Tecartus™) and liso-cel (Breyanzi®).
CD19-directed CAR T therapy is now approved to treat a range of
B-cell malignancies including childhood B cell acute lymphoblastic leukemia and
adult large B cell lymphoma, primary mediastinal large B cell lymphoma, mantle
cell lymphoma and follicular lymphoma. These therapies have provided
significant complete response rates that can last for years. The therapy may
actually eradicate the disease yielding cures; the duration of the effect is
still being evaluated as some patients have been cancer-free for nearly a
decade.
Ide-cel is the first CAR-T that targets a
different protein
Ide-cel works by targeting a protein called BCMA that plays a key
role in multiple myeloma. The FDA approval was based on results from the phase
2 KarMMa study, which treated 127 patients with advanced forms of multiple
myeloma. While multiple myeloma care and outcomes have improved, the disease
remains incurable and patients like the ones in the KarMMa study, whose
cancer has progressed despite treatment with at least three
previous therapies, face poor survival rates.
The majority (72%) of patients in the trial partially or
completely responded to ide-cel treatment, with 28% having a complete
response—disappearance of all signs of multiple myeloma. Among those with
a complete response, 65% remained in complete response for at least 12 months.
The known side-effects for CAR T therapy were reported for ide-cel with marked
cytokine release syndrome (CRS) and CAR T cell-associated
neurotoxicity, occurring in 85% and 28% of patients, respectively, both of
which were usually transient.
Multiple myeloma is most common among older patients who also face
the worst prognosis and often have limited treatment option. Ide-cel was
similarly effective in patients 65 and older, and even in those 70 and older,
as it was in the overall study group. Perhaps most importantly, patients
treated with ide-cel had improved quality of life. They reported meaningful
improvements in most symptoms and their ability to perform day-to-day
functions.
About multiple myeloma
Multiple myeloma is a cancer derived from a specialized type of
white blood cell called a plasma cells. Such malignant cells proliferate
uncontrollably leading to impairment of normal blood cell function, and in
advanced cases leads to kidney impairment and bone destruction. While the
disease is considered incurable, and the relative five-year survival rate for
patients diagnosed with multiple myeloma in the US is approximately 50%, the
addition of multiple new FDA-approved therapies to treat the disease are likely
to increase overall survival rates in the future.
In 2021, there were 34,920 new cases of multiple myeloma
associated with 12,410 deaths in the US. This accounts for approximately 20% of
all new cases and deaths from blood cancers in the US. Myeloma is the second
most common blood cancer in the U.S. and the most prevalent among African
Americans. It is also the hematologic malignancy with the greatest racial
disparity in incidence and prevalence; Blacks are not only at twice the risk of
developing this rare and incurable cancer when compared to white Americans and
other ethnic groups, they are also more likely to be diagnosed at a younger
age.
In response to these inequalities, LLS launched a national
outreach program in 2017 called “Myeloma Link” to educate African Americans about
myeloma, and to help patients access optimal care, and navigate the treatment
landscape more effectively.
LLS is looking to the future for better myeloma
care and improved CAR-T options
While today’s approval is a step forward, we believe blood cancer
is curable and we pledge to be unstoppable in our quest. We have 22 currently
active grants focused on multiple myeloma supporting world-class researchers
studying a range of novel treatment options.
We also support the power of partnerships. LLS Specialized Center
of Research (SCOR) grants are designed to bring together established
investigators to foster new interactions and cooperation to speed development
of innovative strategies and approaches to blood cancers. In January 2020, LLS
activated two SCOR grants investigating the use of CAR-T in multiple myeloma,
to Carl June M.D., at the University of Pennsylvania and Madhav Dhodapkar MBBS,
at Emory University in Atlanta, investing a combined $7.5M into their promising
research.
LLS has also been at the forefront of CAR-T research and that is
where we remain. Our current focus is on research to make CAR-T available for
more types of cancer, by expanding the proteins targeted, and to make it less
costly and quicker to administer. To speed the process and lower costs,
LLS-funded researchers are working on “off the shelf” CAR T-therapies that use
donor T cells instead of having to harvest and re-engineer each individual
patient’s T-cells before reinfusing them.
We are also supporting research into immunotherapies using
other parts of the immune system—beyond T cells—to express the Chimeric
Antigen Receptor that gives CAR its name. Researchers are finding new ways to
add the CAR receptor, which helps immune cells find and kill cancer cells that
use natural killer (NK) cells or macrophages. These cells may provide longer
lasting anti-tumor activity than traditional CAR-Ts and may also be useful for
treating diseases beyond cancer.
We often connect one name to major scientific discoveries.
Alexander Graham Bell and the telephone or Thomas Edison and the light bulb,
among many others. But the reality is that medical breakthroughs are almost
always based on years of research, collaboration, information sharing, and
stepwise clinical trials that test the safety and efficacy of novel and
re-purposed treatments over years. LLS has been committed to this process for
more than 70 years, but today we’re also finding ways to speed it up, and the
pace of new immunotherapies is proof of our—and the entire field’s—success.
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