Doing the Numbers

Cancer is a numbers game.

This can be both good or bad.  The good news is that everything cancer is studied and published and this information is now available to all.  The bad news it that as a patient sometimes you just feel like a number.

The reality is that we are all just numbers, and this can work against the patient who is seeking the best outcome - in other words, it's not always in the best interest of "the numbers" to stray from the standard protocols.

After "failing" first line treatment, and with no response to Brentuximab,  I started "doing the numbers" on the recommendation for a stem cell transplant.  And the numbers are telling me that I'm going to have to work really hard to beat the odds.


According to Hodgkin lymphoma: 2016 update on diagnosis, risk-stratification, and management.

Management of relapsed/refractory disease: High-dose chemotherapy (HDCT) followed by an autologous stem cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy. For patients who fail HDCT with ASCT, brentuximab vedotin, PD-1 blockade, nonmyeloablative allogeneic transplant or participation in a clinical trial should be considered.

SEOM clinical guidelines for the treatment of Hodgkin's lymphoma.

In general, the new "immunotherapy" drugs are reserved for those who fail stem cell transplant (ASCT)

According to the journal article, Salvage Therapy in Hodgkin's Lymphoma:

The majority of patients with Hodgkin's lymphoma (HL) are cured with first-line therapy; however, approximately 15%–20% of patients with stage I–II HL and 35%–40% of patients with stage III–IV HL and risk factors relapse after first-line therapy

The current standard of care for patients with relapsed or refractory HL results in cure approximately 50% of the time. 

Multiple single-arm studies incorporating both relapsed and refractory HL patients have demonstrated that a salvage approach incorporating HDCT/ASCT results in durable PFS and OS rates in the range of 40%–50% and 50%–60%, respectively [3, 6, 23–26]. Importantly, patients with refractory disease generally do worse, with durable PFS and OS rates in the range of 15%–32% and 26%–36%, respectively [7, 8, 23, 27, 28].

In addition to refractoriness to initial chemotherapy, several other factors have been identified in the relapsed/refractory HL setting that predict a worse prognosis. 

Brice et al. [31] used two adverse prognostic factors (end-of-treatment to relapse interval ≤12 months and extranodal relapse) to predict outcome in a French population of patients receiving ASCT. Patients with zero, one, or two of these factors had 4-year OS rates of 93%, 59%, and 43%, respectively.
In a prospective study, Moskowitz et al. [15] demonstrated that B symptoms, extranodal disease, and time to relapse <12 months influenced outcome after ASCT. Patients with none or one of these factors had a 43-month EFS rate of 83%, compared with 27% and 10% for patients with two or three factors, respectively.

These studies demonstrate that it is possible to use distinct clinical features at relapse to make general predictions about the likelihood of success with HDCT/ASCT.

Patients with refractory disease or poor-risk relapse are unlikely to do well with this modality and should be considered for other options.  

Relapse after ASCT generally portends a poor prognosis, with a median survival duration in the range of 24 months



This data suggests that in my case, with immediate relapse/refractory disease, advanced stage with B symptoms, bone marrow involvement, and extra nodal disease (spleen, etc) I am unlikely to do well with autologous stem cell transplant.


More research suggests that; Patients with classical Hodgkin lymphoma experiencing disease progression after treatment with brentuximab vedotin have poor outcomes.

Optimal management of patients with HL requires an accurate diagnosis and careful staging of the disease. Identification of poor prognostic features then allows for risk-adapted therapy to potentially increase the likelihood of cure and minimize toxicity. Future directions to further improve the outcome of patients with HL will include incorporating into frontline therapy those agents that are effective in the relapsed setting.




A recent article in the New York Times provides some hope.


For decades, he explained, oncologists had treated relapsed Hodgkin’s lymphoma in a standard manner. “There were limited options,” O’Connor said. “We gave some patients more chemotherapy, with higher doses and more toxic drugs, hoping for a response. For some, we tried to cure the disease using bone-marrow transplantation.” But the failure rate was high: About 30 percent of patients didn’t respond, and half of them died.

Then a year or two ago, he tried something new. He began to use immunological therapy to treat relapsed, refractory Hodgkin’s lymphoma. Immunological therapies come in various forms. There are antibodies: missile-like proteins, made by our own immune systems, that are designed to attack and destroy foreign microbes (antibodies can also be made artificially through genetic engineering, armed with toxins and used as “drugs” to kill cancer cells). And there are drugs that incite a patient’s own immune system to recognize and kill tumor cells, a mode of treatment that lay fallow for decades before being revived. O’Connor used both therapies and found that they worked in patients with Hodgkin’s disease. “We began to see spectacular responses,” he said.

Doing the numbers, and asking the questions…

Seeking a second opinion, and hoping to find a Dr that able to step out of the box and apply a "risk-adapted therapy to potentially increase the likelihood of cure and minimize toxicity."

Otherwise, I'm going to end up a number...




References:

Hodgkin lymphoma: 2016 update on diagnosis, risk-stratification, and management.

SEOM clinical guidelines for the treatment of Hodgkin's lymphoma.

 Salvage Therapy in Hodgkin's Lymphoma
    Jason H. Mendler and Jonathan W. Friedberg, James P. Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York, USA. First published online in THE ONCOLOGIST Express on April 2, 2009.
 
Patients with classical Hodgkin lymphoma experiencing disease progression after treatment with brentuximab vedotin have poor outcomes.


 The Improvisational Oncologist, New York Times magazine, May 15, 2015