The Hype of Cancer Immunotherapy

choi

Ron Winslow, Super-Survivors Fuel Cancer Hope. Wall Street Journal, Dec 5, 2014 (front page; under the heading “Early Promise”).
online.wsj.com/articles/cancers-super-survivors-how-immunotherapy-is-transforming-oncology-1417714379

Quote:

"Cancer immunotherapy comes in several forms. The drugs sparking the most interest are called checkpoint inhibitors. They work by releasing the natural brakes on the immune system, enabling its foot soldiers, called T cells, to attack tumors.

"It is hard to know how many patients whose cancers have metastasized, or spread, have enjoyed sustained survival following immunotherapy treatment. An analysis of 4,846 advanced melanoma patients treated with one checkpoint inhibitor— Bristol-Myers Squibb Co’s Yervoy—found that 21% were still alive three years later. * * * Especially striking is how good the long-term prospects were for people who survived at least three years.

"James Allison [PhD], head of immunology at MD Anderson Cancer Center in Houston, whose seminal discovery about the immune system and cancer in the mid-1990s [at University of California Berkeley] laid the groundwork for many of the current advances.

"Newer drugs that work similarly to Yervoy, but on different immune-system brakes, are getting even better early results and are extending the benefits beyond melanoma to other cancers.

In cancer immunotherapy, "most patients don’t respond the way the super-survivors have [eg, 79% of those who takes Yervoy (quotation 2)]

"While side effects of the new drugs [in cancer immunotherapy] are relatively mild for some patients, others have developed potentially devastating complications caused by an out-of-control immune system [supposedly due to the releasing of the natural brakes on the immune system (quotation 1); supposedly, because molecular mechanisms have not been worked out--nobody really knows for sure what is going on; the concept of a brake in immune system is unproven]. Some patients have died as a result.

"Bert Vogelstein [MD], director of the Ludwig Center at Johns Hopkins Kimmel Cancer Center in Baltimore[:] 'But the reality is that most are not [responding to checkpoint inhibitors].'

"Yervoy costs more than $120,000 for a four-course treatment, while Merck & Co’s Keytruda, approved in September for advanced melanoma, costs $12,500 a month, or $150,000 for a year.

"Bristol-Myers’s drug Yervoy, which is based on Dr Allison’s discoveries, blocks an immune system brake called CTLA-4. Merck’s Keytruda inhibits a brake called PD-1.

"Another approach involves genetically modifying certain T cells outside the body, creating what are called CAR T cells [where CAR stands for 'chimeric antigen receptor'], and infusing them back to attack targets on the surface of cancer cells. Novartis AG , closely held Juno Therapeutics Inc, Kite Pharma Inc., and a collaboration between Bluebird bio and Celgene are pursuing this strategy.

"most current cancer treatments, including chemotherapy, radiation * * * take direct aim at the tumor * * * With immunotherapy, 'We’re treating the immune system, not the cancer,' says Dr Allison.

"For years, scientists thought the immune system didn’t recognize tumors at all. Then research on biopsy specimens revealed that T cells often succeed in infiltrating the environment around tumors, but either fail to mount an adequate response or hold the cancer at bay for years before finally being overmatched.

"The challenge was to widen the benefit to more patients and more cancers. For reasons of biology, melanoma is more vulnerable than most other tumor types to attacks by the immune system. For immunotherapy to become a mainstay of cancer treatment, it needs to prove effective against more tumors.

choi

My comment:
(a) Before you read the text, go down mid-page to view the graphic (titled “An Innovative Approach to Cancer of five panels.
(b) All “drugs” listed in this report are all monoclonal antibodies directed against either CTLA-4 or PD-1 (that is why their USAN names ends with “mab.” See drug nomenclature
en.wikipedia.org/wiki/Drug_nomenclature
(United States Adopted Name (USAN); section 3 List of drug name stems and affixes: -mab = Monoclonal antibodies)

(c) "Mr [Tom] Telford looked forward to relaxing on a 25th anniversary cruise with his wife. But once in the Caribbean, he struggled to swim and climbing from one deck to another exhausted him. Back at home, he collapsed while running a TV cable in his bedroom."
(i) deck (n): "2: something resembling the deck of a ship: as
a :  a story or tier of a building (as a sports stadium) <the upper deck>"
www.merriam-webster.com/dictionary/deck
(ii) run: "SOMETHING LONG [intransitive,transitive always + adverb/preposition]    if something long such as a road or wire runs in a particular direction, that is its position, or that is where you put it:
<The road runs along a valley>
<Developers want to run a road right through his farm>
<Run the cables under the carpet>
<The Sierra mountain range runs the length of the north west coast of Majorca>"
Longman Dictionary of Contemporary English, undated.
www.ldoceonline.com/dictionary/run_1

(c) “I’m pretty even-keel and take it as it comes.”

even-keeled (adj; First Known Use 1945): "characterized by stability or consistency"
www.merriam-webster.com/dictionary/even-keeled
(d) "David Gobin, a retired Baltimore policeman, was diagnosed with lung cancer at 58. He lost much of his right lung to surgery * * * In late 2010, he joined a trial at Johns Hopkins for an experimental Bristol-Myers drug [now called nivolumab] that blocks the immune system brake called PD-1. * * * Mr Gobin gets short of breath because of the lung surgery, and he needs to take frequent rests [because he has only one lung]. He isn’t complaining."

Later in the report was another “anti-PD-1 agent being developed by Merck that became known as Keytruda.”
(e)
(i) The last quotation says it all. It has been known for decades that melanoma is a special case for cancer immunotherapy. For unknown reasons, melanomas simply are susceptible to various forms of this therapy. Melanoma accounts for 5% of cancers in US, but are rare among Asians (mostly likely because we have more pigments in the skin).
(ii) CDC statistics show that for both males and females,melanoma incidence rate 發病率 (as well as death rate 死亡率) is white> (Hispanic= American Indian) > (Asian/Pacific islander = black).