Narrator: RESPONSE Trial With Jakafi® (ruxolitinib): Efficacy and Safety Data
Narrator: Jakafi® (ruxolitinib) is indicated for treatment of patients with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea.
Dr Erba: Hello, my name is Harry Erba. I'm a professor of internal medicine at the University of Alabama at Birmingham where I serve as the director of the hematologic malignancies program as well as the associate director of the cancer center for clinical research. For the last 20 years, I've been a clinical investigator evaluating novel therapies for people with myeloid neoplasms including the myeloproliferative neoplasms.
Narrator: This promotional presentation is being sponsored by Incyte Corporation.
Dr Erba: We're going to speak about the labeled indication for Jakafi® (ruxolitinib) for patients with polycythemia vera who have had either an inadequate response to or are intolerant of hydroxyurea.
Dr Erba: The information that I will present is all consistent with the labeled indication and consistent with FDA regulations. We will also discuss important safety information regarding Jakafi.
Narrator: The RESPONSE Trial. A Randomized study of Efficacy and Safety in POlycythemia vera with JAK iNhibitor ruxolitinib verSus bEst available care.
Dr Erba: Let's now review the RESPONSE trial design. The RESPONSE trial was a randomized Phase III study that compared Jakafi to best available therapy for patients with polycythemia vera who were either intolerant of or had an inadequate response to hydroxyurea as defined by the European Leukemia Network.
Dr Erba: Patients had to have a persistent phlebotomy requirement and…measurable splenomegaly by MRI.
Dr Erba: There was a pre-randomization phase where all of the patients were kind of brought to the same starting gate.
Dr Erba: The hematocrit had to be controlled to less than 45%. And then they were randomized between Jakafi 10 milligrams twice daily or best available therapy.
Now what I find interesting about this clinical trial is that the patients who were randomized to best available therapyand remember they were intolerant of or had an inadequate response to hydroxyureaalmost 60% stayed on or received hydroxyurea.
Dr Erba: The primary analysis was done at 32 weeks. The primary end point was a composite of hematocrit control with freedom from phlebotomy as well as a 35% or more reduction in splenic volume by MRI.
Narrator: More specifically, to achieve the Hematocrit Control end point, patients could not become eligible for phlebotomy between weeks 8 and 32. Phlebotomy eligibility was defined as hematocrit >45% that is ≥3 percentage points higher than baseline or hematocrit >48%, whichever was lower.
Dr Erba: The two groups were well matched for age, gender.
About half of the patients in both groups had resistance to and the other half intolerance of hydroxyurea.
Many of these patients had prior thromboembolic events.
As you can see, patients had a hematocrit less than 45% at the time of randomization. However, the median white blood cell count and platelet count were above normal.
Narrator: RESPONSE: Efficacy data
Dr Erba: Twenty-three percent of patients treated with Jakafi achieved the composite end point versus only less than 1% of patients on best available therapy.
And in fact, at 48 weeks, 22 of the 25 patients maintained the composite end point.
Dr Erba: Jakafi demonstrated superior results compared to best available therapy at 32 weeks in these patients.
Dr Erba: In terms of hematocrit control that was achieved in 60% of patients receiving Jakafi versus only 19% of patients on best available therapy. Likewise, for control of splenomegaly with a decrease in splenic volume by 35% or more as measured by MRI, that was achieved in 40% of patients that were receiving Jakafi versus less than 1% of patients on best available therapy.
Dr Erba: Furthermore, Jakafi demonstrated higher rates of complete hematologic remission compared to best available therapy in this population of patients. Remember complete hematologic remission is defined as hematocrit less than 45% without a phlebotomy requirement, white blood cell count less than 10,000 and platelet count less than 400,000.
Dr Erba: Twenty-four percent of patients treated with Jakafi achieved a complete hematologic remission at 32 weeks compared to 8% with best available therapy.
Dr Erba: Now let's look at the durability of the key secondary and the primary end points in the RESPONSE trial.
First of all, 83% of patients who were receiving Jakafi at study entry were still receiving Jakafi at 80 weeks.
Dr Erba: In terms of the composite primary end point 76% of patients who had achieved it at 32 weeks were still in that composite end point at 80 weeks. Fifty-eight percent of patients who had achieved a complete hematologic remission at 32 weeks maintained it at 80 weeks.
Dr Erba: And if you look at the components of that composite end point, hematocrit control and control of splenomegaly, the responses were durable. It was 77% of patients at 80 weeks who had achieved a hematocrit control of 32 weeks were still maintaining it.
And in terms of controlled splenomegaly only one patient was no longer in response at 80 weeks. Ninety-eight percent of patients who had control of splenomegaly at 32 weeks maintained that response by 80 weeks.
Narrator: Important Safety Information
- Treatment with Jakafi® (ruxolitinib) can cause thrombocytopenia, anemia and neutropenia, which are each dose‐related effects. Perform a pre‐treatment complete blood count (CBC) and monitor CBCs every 2 to 4 weeks until doses are stabilized, and then as clinically indicated
- Manage thrombocytopenia by reducing the dose or temporarily interrupting Jakafi. Platelet transfusions may be necessary
- Patients developing anemia may require blood transfusions and/or dose modifications of Jakafi
- Severe neutropenia (ANC <0.5 × 109/L) was generally reversible by withholding Jakafi until recovery
- Serious bacterial, mycobacterial, fungal and viral infections have occurred. Delay starting Jakafi until active serious infections have resolved. Observe patients receiving Jakafi for signs and symptoms of infection and manage promptly
- Tuberculosis (TB) infection has been reported. Observe patients taking Jakafi for signs and symptoms of active TB and manage promptly. Prior to initiating Jakafi, evaluate patients for TB risk factors and test those at higher risk for latent infection. Consult a physician with expertise in the treatment of TB before starting Jakafi in patients with evidence of active or latent TB. Continuation of Jakafi during treatment of active TB should be based on the overall risk‐benefit determination
- Progressive multifocal leukoencephalopathy (PML) has occurred with ruxolitinib treatment for myelofibrosis. If PML is suspected, stop Jakafi and evaluate
- Advise patients about early signs and symptoms of herpes zoster and to seek early treatment
- Increases in hepatitis B viral load with or without associated elevations in alanine aminotransferase and aspartate aminotransferase have been reported in patients with chronic hepatitis B virus (HBV) infections. Monitor and treat patients with chronic HBV infection according to clinical guidelines
- When discontinuing Jakafi, myeloproliferative neoplasm-related symptoms may return within one week. After discontinuation, some patients with myelofibrosis have experienced fever, respiratory distress, hypotension, DIC, or multi-organ failure. If any of these occur after discontinuation or while tapering Jakafi, evaluate and treat any intercurrent illness and consider restarting or increasing the dose of Jakafi. Instruct patients not to interrupt or discontinue Jakafi without consulting their physician. When discontinuing or interrupting Jakafi for reasons other than thrombocytopenia or neutropenia, consider gradual tapering rather than abrupt discontinuation
- Non‐melanoma skin cancers including basal cell, squamous cell, and Merkel cell carcinoma have occurred. Perform periodic skin examinations
- Treatment with Jakafi has been associated with increases in total cholesterol, low-density lipoprotein cholesterol, and triglycerides. Assess lipid parameters 8-12 weeks after initiating Jakafi. Monitor and treat according to clinical guidelines for the management of hyperlipidemia
- The three most frequent non‐hematologic adverse reactions (incidence >10%) were bruising, dizziness and headache
- A dose modification is recommended when administering Jakafi with strong CYP3A4 inhibitors or fluconazole or in patients with renal or hepatic impairment. Patients should be closely monitored and the dose titrated based on safety and efficacy
- Use of Jakafi during pregnancy is not recommended and should only be used if the potential benefit justifies the potential risk to the fetus. Women taking Jakafi should not breast‐feed
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Dr Erba: Thank you for listening to this presentation regarding the results of the RESPONSE trial demonstrating the efficacy and safety of the use of Jakafi in patients with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea.