A unique patient perspective of personalized medicine in practice

Jack Whelan shares his personal journey as a patient with a rare blood cancer and his unique experiences with clinical trials. As our personalised medicine month continues, Jack discusses how targeted therapies are truly making a difference to patients.

You’re told you have a rare, incurable blood cancer. What would you do?

I knew something was wrong when my daily walk to the financial district from Boston’s North Station caused a shortness of breath and nosebleeds. The afternoon fatigue signaled all is not well. I thought get that annual physical now. Sensing my primary care physician had already done some research, I wasn’t surprised when he suggested seeing an oncologist who after reviewing some blood work quickly scheduled my first of many bone marrow biopsies. The next day in a confident upbeat tone, the oncologist asked, can you come in and see me? Today? Yikes!

Dana Farber Cancer Institute (DFCI), known for state-of-the-art research and care, confirmed Waldenström’s Macroglobulinemia, (WM) a rare indolent B cell malignancy showing lymphoplasmacytic cells infiltrating 80% of the bone marrow and a very high immunoglobulin M (IgM). About 1500 new cases are diagnosed each year in the U.S. It was first described by oncologist Ian Waldenstrom in 1944, yet there is still no “silver bullet”.

As a cancer of the bone marrow, it can’t be radiated or surgically removed. Headaches and nosebleeds, the pain of peripheral neuropathy from nerve signals gone awry can be reduced by a four hour plasmapheresis, a temporary measure that mechanically filters the large “macro” globulins from our white blood (plasma) cells. A high IgM is dangerous. This plasma exchange reduced symptoms, but did nothing to solve the underlying problem.

My oncologist explained a variety of treatment options that might help. Options, I know options. As a career IT Research Analyst having seen the benefits of good science, I wanted to weigh those options so I researched wide and deep to be comfortable with any decision I would make with my oncologist.

“I eagerly embraced the promise of personalized medicine – “the right medicine, for the right patient at the right time”.”


Not impressed with the then historical five year median survival and side-effects of conventional chemotherapy of alkylating agents and nucleoside analogs “borrowed” from other blood cancers and reports of transformation to a more aggressive cancer in WM patients who had been treated with these, I was eager to learn more when my oncologist Dr. Irene Ghobrial suggested exploring emerging therapies now in clinical trials1,2. I asked how safely can we kill cancer in the bone marrow — the factory floor that produces blood? What about this personalized or precision medicine stuff? Don’t you (we) have some kind of targeting agent to stop this progression?

During my term in the U.S. Navy, I learned much about Naval Tactical Data weapons Systems, (NTDS) that identify the right target, hit it with the right payload using the right delivery mechanism at the right time. These are very effective and cause little collateral damage. So naturally, I eagerly embraced the promise of personalized medicine – “the right medicine, for the right patient at the right time“. Bring it on, I said. Dr. Irene said, not so fast, we’re not quite there yet. We’re close.

I remembered if the NTDS is inoperable for any reason, use empirical information to home in on the target. Fire at the target and adjust your range and bearing as needed. Keep trying until you hit it. Meanwhile, learn as much as you can about the target after each shot. That’s the approach we took to beat my blood cancer with these new targeting agents.

In oncology, rather than using empirical information centered on the type of weapon (drug) let’s use genetic and genomic information centered on the target (cancer) in the patient.

“In the U.S., less than 4% of cancer patients participate in clinical trials…”


I’ve had a front row seat seeing the development of personalized medicine and realizing its benefits. I began the cautious journey in clinical trials and became an e-patient. These are educated, empowered, engaged, internet-savvy patients that take a keen interest in their disease and care. I embrace forward-looking science such as biomarker validation.

There are too many myths & misconceptions about clinical trials: the guinea pig, last resort, high cost, placebo, no insurance and only at large institutions. In the U.S., less than 4% of cancer patients participate in clinical trials; that means 96% get “standard care”.

I believe my targeted therapy care far exceeded the standard care. Rituximab is a monoclonal antibody against protein CD20 found on normal and malignant B cells. For many, this effective immunotherapy induces apoptosis (kills) of CD20+ cells. We fired at all CD+ B cells. Unfortunately, I was refractory, I didn’t respond. We then tried Bortezomib a proteasome inhibitor, an enzyme complex that blocks much-needed protein which in turn causes apoptosis. Bortezomib is associated with peripheral neuropathy in 30% of WM patients; from clinical trials researchers later learned a new delivery mechanism (subcutaneous) rather infusion was more suitable. We then blocked a communications line with Enzastaurin is a kinase inhibitor that targets protein kinase C-beta (PKCβ) and PI3K/AKT signaling pathways. And later, Everolimus an oral agent mTOR inhibitor that targets raptor mTOR, a signaling pathway which controls cell proliferation and survival. Finally, Panobinostat which gave this patient the overall best response is a novel histone deacetylase inhibitor (HDAC inhibitor) that causes apoptosis of malignant cells by blocking multiple pathways. This is the best I have felt in six years!

“I believe my targeted therapy care far exceeded the standard care.”


I can honestly say I don’t participate in clinical trials for any altruistic reason. I believe it is the safest, most effective treatment option for my type of uncommon, incurable blood cancer and it’s good option to manage and achieve my current state of progression free survival, even if temporary.

So where are we today? We’ve learned much about identifying the right target and how to interfere with important enzymes, signals and pathways. As an integral part of personalized medicine, we recently learned whole genome sequencing of lymphoplasmacytic cells in 90% of WM patients reveals a widely expressed mutation- Myeloid differentiation factor 88 (MYD88) at amino acid position 265 from leucine to proline (L265P) in the DNA of WM patients, rarely seen in other lymphoproliferative or plasmaproliferative malignancies3.

This means we have now have a reliable target; perhaps not the only target. Researchers have determined that a Bruton’s tyrosine kinase inhibitors (BTK) such as Ibrutinib and AVL-292, also known as CC-292 affect survival of WM lymphoplasmacytic cells and the more common SLL, CLL, DLBCL, MCL and MM blood cancers4. We now have the delivery mechanism and payload. We need more research studies to determine what if any collateral damage could occur downstream.

The evidence suggests these types of molecular level targeting agents will prove to be safer and more effectives than many currently available conventional chemotherapies. This writer believes there is an urgent need for greater participation in clinical trials, more likely safer than the standard of care for many.


1. Median overall survival of patients with WM is 5-6 years . Update: The median disease-specific survival of symptomatic WM is 11.2 years. Paper ; Ghobrial IM, MD, Are you sure this is Waldenström’s Macroglobulinemia, ASH Education Program, 2012;2012:586-94 . Doi: 10.1182/asheducation-2012.1.586

2. Journal of Clinical Oncology, December 10, 2008 Increased Incidence of Transformation and Myelodysplasia / Acute Leukemia in Patients with Waldenstrom Macroglobulinemia Treated with Nucleoside Analogs, also update from Leleu X, Sourmerai J, Roccaro, A, et al, J Clin Oncol, 2009;27:250-255

3. Treon S, Xu Lian, et al. Whole genome sequencing reveals mutation (MYD88 L265P) in WM. Blood ASH Annual Meeting abstracts 2011;118(21);300

4. Ghobrial IM. Are you sure this is Waldenstrom Macroglobulinemia? Hematology American Society of Hematology Educational Program. 2012;2012:586–594.


About the author:

Jack Whelan is transitioning from a career as an IT Research Analyst to a Research Advocate recommending cancer patients explore Clinical Trials and the promise of Personalized Medicine. He’s an associate member of American Association of Cancer Research completing the 2013 Scientist-Survivor program, active with American Society of Clinical Oncology completing the Research Advocate Institute 2013 Scholar program and the Drug Information Association 2013 Patient Advocate Fellowship. He is New England Support Group Leader for the International Waldenstrom’s Macroglobulinemia Foundation, active with Leukemia & Lymphoma Society in advocacy and legislative circles such as the Oral Chemotherapy Parity and Step Therapy Legislation. He is a member of the Dana Farber Patient Family Advisory Council and for the past two years Jack has supported fundraising for DFCI as a volunteer speaker on radio and TV (WEEI and NESN-TV ) for the Jimmy Fund annual Telethon and the institution’s recurring network TV commercials about his treatment at DFCI. He is an exciting, fun and informative speaker with a thoughtful patient’s voice at leading oncology, pharma and healthcare conferences.

Jack lives in Andover MA with his wife Jan, father of three married daughters and great sons-in-law and grandfather of twin granddaughters. He has an advocate web site at Jack-Whelan.com.

How can we overcome the challenges of clinical trial patient recruitment?