Seismic Shifts: A Brief History of Blood Cancer

I’ve lived in California’s Bay Area for more than 30 years, so I’m no stranger to the feeling of the earth moving under my feet. The trembling ground signals profound shifts in the landscape around you. This is happening right now – not in the earth’s crust, but in the world of blood cancer.

We’re in the midst of a dramatic transformation. As my colleague Nancy Valente explained in her history of ASH, hematology has changed profoundly over the past several decades. Today, the outlook for many people with blood cancer is promising, and it may even get better.

But this change didn’t happen overnight. The world of blood cancer today is the product of a long and complicated history, with heartbreak and hope spanning everywhere from the bench to the bedside – and even the battlefield.

Deep foundations

The story of blood cancer goes back thousands of years. Fossil records show evidence of the effects of blood cancer, and an illness like leukemia was observed by the ancient Greeks. However, it wasn’t until British doctor Thomas Hodgkin published the first description of lymphoma in 1832 that clinical diagnoses began. Leukemia and myeloma followed soon after.

Over the next century, doctors refined their understanding of these diseases. They discovered important distinctions: Hodgkin’s vs. non-Hodgkin’s lymphomas, chronic vs. acute leukemias, lymphocytic vs. myeloid leukemias, and many more subtle classifications that have resulted in more than 100 subtypes. However, though our understanding steadily advanced, our ability to treat them lagged decades behind.

Unintended discovery

The first step toward closing that gap was taken in the early 20th century, when new discoveries like x-rays and radioactive elements made the first radiation therapies for lymphoma possible.

The next glimmer of hope had a tragically dark origin: chemical warfare in World War I. Doctors and scientists discovered that one of the most deadly weapons, mustard gas, stopped new blood cells from forming (hematopoiesis). This led to the idea that in limited doses, these poisonous compounds might be harnessed to fight blood cancer.

A mustard gas-based treatment was the first chemotherapy to achieve durable remissions in lymphoma.

The next breakthrough was the bone marrow transplant. In yet another tragic irony, this discovery rose from the ashes of the atomic bomb in World War II. The bone marrow of victims in Japan was completely destroyed, leading doctors to speculate that in lower doses radiation could eliminate the cancerous cells that cause leukemia (a disease which originates in the bone marrow). The patient’s bone marrow could then be replaced with healthy donor tissue. This radical idea was successfully carried out in the 1960s.

Exploring new vistas

Radiation, chemotherapy, and bone marrow transplants truly shook up the world of blood cancer. After so many centuries of helplessness, doctors and patients finally had tools to fight back.

But as powerful as the new therapies were, they could never fully shake their belligerent roots. These tamed weapons indiscriminately attack cells of the patient’s body along with the cancer. To move forward, we needed a fundamentally different approach: a “magic bullet” that targets the cancer.

So began the era of targeted therapy, perhaps the greatest revolution in the history of cancer. And it all started in blood cancer.

The first targeted medicine ever approved by the FDA was an antibody that hunts down the cells that comprise non-Hodgkin’s lymphoma, based on a specific marker on the cell surface.

Other targeted therapies soon followed. Some were antibodies and others were molecules that disrupted cancer signals. All of this was made possible by scientific progress that helped us understand cancer at a molecular level.

Reshaping the landscape

The impact of this first wave of targeted therapies was monumental. One of the most dramatic effects was the reversal of rising mortality rates for non-Hodgkin’s lymphoma (see timeline below).

U.S. Blood Cancer Mortality Rates 1969 to 2010

Click on specific blood cancer types below to turn individual graph lines off/on.

But the timeline also highlights another fact: progress has not been felt equally across all blood cancers. For people still fighting these devastating diseases, more options are badly needed.

That brings us to the present day. ASH 2013. And the rumbling ground beneath our feet.

Big changes are upon us

The evidence is in the numbers: seven FDA breakthrough therapy designations for blood cancers, more than 100 orphan drug designations for leukemia alone, and a massive industry-wide biopharmaceutical pipeline with nearly 250 investigational medicines in development for leukemias, lymphomas, and other blood cancers.

At ASH this year, we’ll review data from many of these investigational medicines, representing every stage of development from preclinical experiments in single labs to large, late-stage clinical trials spanning the globe.

The diversity of data is remarkable. It reflects exponential growth in the number of therapeutic targets identified by scientific research and their translation to the clinic. Anticipation is particularly high for new data in chronic lymphocytic leukemia (CLL), a disease marked by incremental therapeutic progress that’s now been recognized with multiple breakthrough therapy designations.

In all the time I’ve worked in hematology and oncology, I’ve never sensed more excitement around ASH than I do this year. Nor has there ever been more hope for people with blood cancer who are anxiously awaiting new treatment options.

The ground is shaking, and as a result, the landscape is looking better than ever.