Change Tx for spleen enlargement after response on Rux? Taper/stop Rux on progression after 1 y of response?
A patient with myelofibrosis was started on ruxolitinib and experienced an initial improvement in symptoms and a decrease in spleen size from 18 cm to 2 cm below the costal margin (BCM). The patient now presents with an enlarged spleen at 6 cm BCM but still feels well. Should the therapy be changed?
A patient initially responds to ruxolitinib therapy for approximately 1 year but subsequently develops disease progression, and a decision is made to discontinue treatment. Should the ruxolitinib be tapered or stopped abruptly?
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Jason Gotlib, MD, MS |
| Associate Professor of Medicine (Hematology) Stanford University School of Medicine/Stanford Cancer Institute Stanford, California |
I would continue to use ruxolitinib for the patient in the first scenario. In terms of discontinuing ruxolitinib therapy, no data exist for stopping ruxolitinib abruptly versus tapering the patient off treatment, but I generally favor tapering the treatment over 7 to 10 days. This is a homegrown approach based on clinical judgment.
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Elias Jabbour, MD |
| Associate Professor Leukemia Department The University of Texas MD Anderson Cancer Center Houston, Texas |
If the patient remains asymptomatic and feels well, a 4-cm increase in the size of the spleen will not prompt me to change therapy. I would keep the patient on ruxolitinib, but I would not increase the dose.
For the second scenario, I would taper off ruxolitinib therapy unless the patient is experiencing side effects.
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John O Mascarenhas, MD |
| Myeloproliferative Disorders Program Tisch Cancer Institute Division of Hematology/Oncology Mount Sinai School of Medicine New York, New York |
In the first clinical scenario, I would continue treatment with ruxolitinib. However, I would be prepared to change therapy because it is likely that the patient will experience a further loss of response with a return of symptoms with time.
I try to taper ruxolitinib if it is a scenario in which I know that the drug will be discontinued. If there is an acute reason to take them off treatment, such as platelet count drops to 10K/µL, I would have to stop the drug. Then I would administer 30 mg per day of prednisone and taper that over the next week or so. That tends to buffer some of the rebound effects.
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Ruben A Mesa, MD |
| Chair, Division of Hematology and Medical Oncology Deputy Director, Mayo Clinic Cancer Center Professor of Medicine Mayo Clinic in Arizona Scottsdale, Arizona |
I would not change therapy for this patient in the first example and would continue to administer ruxolitinib.
I tend to taper patients off ruxolitinib over at least 2 weeks.
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Jerry L Spivak, MD |
| Professor of Medicine and Oncology Director, The Johns Hopkins Center for the Chronic Myeloproliferative Disorders Johns Hopkins University School of Medicine Baltimore, Maryland |
We have the issue that when following patients, durability of response to ruxolitinib is only at the 65% level and then patients start to slip. The slippage that I have seen is in spleen size. Spleen size reduction is one benefit that can be derived from ruxolitinib, but there are others. In this first case, I would stay the course and not change therapy. I have observed that patients tend to keep faring well if they remain on therapy despite their spleen getting a little bigger.
So far I have not taken any patient off of ruxolitinib. The question is: What do we mean, “Ruxolitinib is no longer working”? The slippage that I have observed is an increase in spleen size. I have stayed the course and, even though the spleen size may be increasing, the patients continue to fare well.
I can envision a scenario where symptoms worsen, the spleen is progressively enlarging even with dose escalation and I become concerned about suppressing blood production to a great degree. I haven’t run into that yet, and there is no standard schedule for discontinuing ruxolitinib. However, I would prefer to gradually taper off therapy, depending on the current dose.
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David P Steensma, MD |
| Attending Physician Dana-Farber Cancer Institute Associate Professor of Medicine Harvard Medical School Boston, Massachusetts |
If the increase in spleen size was just a few centimeters as in this first scenario, I would not change therapy but I would adjust the dose of the ruxolitinib while carefully monitoring the patient. If after having done that the disease continued to progress and was becoming symptomatic, then I would change to a different therapy rather than just play with the dose.
For the patient in the second case, I would stop ruxolitinib therapy abruptly.
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Moshe Talpaz, MD |
| Alexander J Trotman Professor of Leukemia Research Associate Director of Translational Research UM Comprehensive Cancer Center Associate Chief, Division of Hematology/Oncology Director, Hematologic Malignancies University of Michigan Medical Center Ann Arbor, Michigan |
I would not change therapy for the patient in the first example. However, I would consider dose escalation because there are no other good treatment options for this patient besides ruxolitinib.
I would taper ruxolitinib in the second clinical scenario. However, if the patient’s symptoms are no longer being controlled, it makes no difference how the treatment is stopped.
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Srdan Verstovsek, MD, PhD |
| Professor of Medicine Chief, Section for Myeloproliferative Neoplasms (MPNs) Department of Leukemia Director, Clinical Research Center for MPNs The University of Texas MD Anderson Cancer Center Houston, Texas |
I would not change therapy for this first patient. However, I would consider increasing the ruxolitinib dose or using additional therapy such as hydroxyurea, depending on the clinical scenario.
I would stop ruxolitinib therapy abruptly in the second scenario. If a patient has already experienced a return of all the symptoms, then tapering does not make any sense. Tapering is suggested when therapy needs to be stopped for a patient with an excellent response to mitigate the return of symptoms.