The blood cancer boom: Nearly 250 meds in development, but plenty left to do
If you are a fan of 1970’s cinema—or if you simply enjoy a good love story—then you may remember the Radcliffe undergrad, played by Ali McGraw, who was diagnosed with leukemia in Erich Segal’s "Love Story." Her diagnosis was automatically assumed to be terminal, and it was, much to the heartbreak and chagrin of her handsome and steadfast love interest, played by Ryan O’Neal.
No longer a death sentence
Forty-five years later, a diagnosis of leukemia, or one of the other major types of blood cancer, lymphoma and myeloma, is not assumed to be fatal. In fact, since 1960, the overall five-year survival rate for leukemia has increased from 14% to 60.3%, according to the Leukemia and Lymphoma Society.
Even more dramatic is the five-year survival rate for children under age 15, with acute lymphoblastic leukemia (ALL). This survival statistic, which was just 3% in 1964, was 92% as of 2010. Even five-year survival rates for myeloma have increased from 12% in the 1960’s to 46.7% in 2010.
An unmet medical need
Yet, despite this vast improvement in therapeutic treatment options and outcomes for blood cancer, according to a recent report from the Pharmaceutical Research & Manufacturers Association (PhRMA), more than 162,000 people will be diagnosed with some type of blood cancer this year, and some of them will not survive.
On the bright side, PhRMA reports that there are currently 247 medicines in development for leukemia, lymphoma, myeloma and other blood cancers.
A decade makes a world of difference
Within the last decade, the blood cancer life-or-death algorithm has shifted inexorably in favor of patients. The simple concept of "having leukemia or lymphoma" is now a complex concept that involves a diagnostic process in which there are 35 different subtypes of leukemia and 50 different subtypes of lymphoma.
Much of the progress that has occurred has been driven by a better understanding of the genetic differences among various types of cancer, and the ability to provide more targeted, less toxic, often personalized treatments to patients. For example, when a patient was diagnosed with chronic lymphocyte leukemia (CLL), which killed about 4,600 people in 2014, the main treatment was a challenging and rigorous chemotherapeutic regimen. Now, however, there are newer, more targeted therapies, including monoclonal antibodies and B-cell receptor pathway inhibitors, such as Pharmacyclics’ wonder drug, Imbruvica (ibrutinib), which was approved by the FDA in late 2013 for second-line treatment of patients with CLL.
In July 2014, the indication was expanded to include patients with CLL with a 17p deletion. Imbruvica has been around less than two years, but it is such a therapeutic powerhouse that analysts are predicting $1 billion in sales this year.
From Gleevec to Blincyto
Likewise, before the approval of the tyrosine kinase inhibitor Gleevec (imatinib) for treatment of chronic myeloid leukemia (CML) in 2001, patients with CML faced relatively poor odds—roughly 30%, compared with a five-year survival rate of 80% with Gleevec. Gleevec was a positive development for CML, but not all patients are able to tolerate it. Fortunately, R&D has continued unabated resulting in more targeted therapies that treat specific mutations of CML by disrupting the signals that drive cancer growth.
Even more recently, the FDA approved Amgen’s Blincyto (blinatumomab) for treatment of refractory ALL, which is associated with a three-to-five month life expectancy. Blincyto was fast-tracked through the FDA review process because of stunning results showing that 43% of Blincyto-treated patients with refractory ALL had a complete response.
What’s in the pipeline?
Current therapies for treatment of blood cancer are without a doubt innovative and a huge improvement over earlier treatment options; however, there is room for a broader range of options, especially in targeted therapies. Towards that end, scientists are developing therapies aimed at addressing remaining unmet needs in blood-related oncology.
One example is the ongoing development of a second-generation tyrosine kinase inhibitor, designed to block activation of the FLT-3 cell receptor, which is mutated in 1/3 of patients with acute myeloid leukemia (AML). This work is critical, because there has not been a new therapy approved for 90% of AML cases in the last 40 years.
There is also ongoing antibody development designed to target the CD38 protein on myeloma cells in patients with multiple myeloma. In addition, various genetic mutation inhibitors are being developed to address advanced hematologic malignancies, including IDH2 genetic mutations. Moreover, there is a fully human monocolonal antibody—a PD-1 inhibitor—in development for treatment of Hodgkin lymphoma.
These are a few examples of a wide range of innovative, and in many cases, immunotherapeutic therapies in development for treatment of blood cancer.
Had "Love Story" been made for contemporary audiences, the beautiful heroine would most likely have survived, resulting in a very different ending—but reflecting the positive reality of blood cancer treatment options in 2015.
- Pharmaceutical Researchers and Manufacturers of America Medicines in developement for leukemia & lymphoma