MF: Undertreatment Risks and Markers for Progression

Harry Erba, MD, PhD:I’ve talked about the COMFORT-II study, but let’s go back to the COMFORT-I study because I think there is an important message there. In that study, patients were randomly assigned to get ruxolitinib or placebo. And so, let’s say that you have a patient who has intermediate 2 or high-risk disease and they’re not terribly symptomatic—a few night sweats, let’s say, their spleen is enlarged but it’s not painful. Is that a patient who you should start on ruxolitinib? And I think the survival data from the COMFORT-l needs to be taken seriously and considered in a patient like that.

Patients with intermediate 2 and high-risk disease, those who were randomized to placebo, even though almost all of them crossed over to ruxolitinib, the survival curve separated after the median time to crossover, which was 9 months, suggested that by delaying exposure to ruxolitinib in an intermediate-risk to a high-risk patient, you may actually be affecting that patient’s chance at long-term survival. Maybe they’ve just been allowed to become more cachectic, susceptible to infections, which is cause of death in this disease, or vascular events. It’s not really clear why it is, but nevertheless, the observation was there in the COMFORT-I study when randomized to placebo.

So, I think this risk stratification is really important. I think hematologists need to take it seriously, recognize that the majority of our patients with intermediate-risk and high-risk disease, and by delaying therapy because they don’t feel that the symptoms are severe enough or the spleen is big enough, you actually may be doing some harm by putting that patient at risk for shorter survival.

If you are following a patient though, if they are completely asymptomatic and they have lower-risk disease, their spleen might be palpable but it’s not symptomatic, this is a patient who you need to follow very closely and you need to ask questions that really get at whether the disease is affecting them. This can be tricky because patients can have symptoms from this disease that they are chalking up to something else—“I have aches in my bones because I’m old and I have arthritis,” or “I have pruritus because my dermatologist says I have eczema,” or “I’m having night sweats because I am going through menopause.”

And so, patients may have been told that they have a whole bunch of symptoms related to a number of diseases whereas the unifying disease may actually be the myelofibrosis. So, I think the treating physician has to keep that in mind when questioning their patients that what they’re going to be told by their patient may actually be due to the myelofibrosis and deserves attention and therapy. Likewise, by physical examination if the spleen is enlarging and grows obviously, let’s say by 5 cm, that’s a sign of disease progression. And that patient should be questioned very closely about symptoms from the spleen, from constitutional symptoms, and considered for therapy with ruxolitinib if that’s the case.

Transcript edited for clarity.

March 2017

• A 67-year old woman presents to her primary care physician with complaints of fatigue, abdominal fullness, night sweats, and 17-lb weight loss over the past 6 months.
• PMH includes hypertension, controlled on enalapril 10 mg
• Abdominal examination reveals spleen palpable 7 cm below the costal margin
• Lab values:
  • HGB: 9.2 gm/dl
  • Platelets: 189 x 10⁹/L
  • WBC: 19 x 10⁹/L
• Bone Marrow Biopsy:
  • MF-3
  • CD34+/CD117+ immunostaining demonstrated 1.2% blasts
  • JAK-V617F mutation
• Diagnosis: Primary myelofibrosis