Image of healthcare professionals and polycythemia vera patient Image of healthcare professionals and polycythemia vera patient

When PV advances beyond what HU can control, intervene with Jakafi

…ruxolitinib as a treatment option for patients with PV who have had an inadequate response to or are intolerant of cytoreductive therapy2

Jakafi is indicated for treatment of PV in adults who have had an inadequate response to or are intolerant of HU.



In the phase 3 RESPONSE* trial, Jakafi demonstrated superior results vs Best Available Therapy (BAT).1‡


BAT=best available therapy; CI=confidence interval; Hct=hematocrit.
a95% CI, 15%-32%
b95% CI, 0%-5%
cA durability analysis was performed at week 80 in the original Jakafi arm.

Image of chart that shows Patients Achieving Composite Primary End Point at Week 32

76% of patients treated with Jakafi who achieved hematocrit (Hct) control and spleen volume reduction at 32 weeks maintained these responses through 80 weeks (18 months) of treatment.1

Durability of primary response at 5 years

*The RESPONSE (Randomized study of Efficacy and Safety in POlycythemia vera with JAK iNhibitor ruxolitinib verSus bEst available care) trial was a randomized, open-label, active-controlled phase 3 trial comparing Jakafi with BAT in 222 patients with PV. Patients enrolled in the study had been diagnosed with PV for at least 24 weeks, had an inadequate response to or were intolerant of hydroxyurea (HU), required phlebotomy for Hct control, and exhibited splenomegaly. All patients were required to demonstrate Hct control between 40% and 45% prior to randomization. After week 32, patients were able to cross over to Jakafi treatment.1,3
The composite primary end point was defined as Hct control without phlebotomy eligibility and a ≥35% spleen volume reduction as measured by computed tomography (CT) or magnetic resonance imaging (MRI). To achieve the Hct control end point, patients could not become eligible for phlebotomy between weeks 8 and 32. Phlebotomy eligibility was defined as Hct >45% that is ≥3 percentage points higher than baseline or Hct >48% (lower value).1,3
BAT included HU (60%), interferon/pegylated interferon (12%), anagrelide (7%), pipobroman (2%), lenalidomide/thalidomide (5%), and observation (15%).1,3


Image of chart that shows Patients Achieving Composite Primary End Point at Week 32

BAT=best available therapy; CI=confidence interval; Hct=hematocrit.
a95% CI, 15%-32%
b95% CI, 0%-5%
cA durability analysis was performed at week 80 in the original Jakafi arm.

76% of patients treated with Jakafi who achieved hematocrit (Hct) control and spleen volume reduction at 32 weeks maintained these responses through 80 weeks (18 months) of treatment.1

Durability of primary response at 5 years

*The RESPONSE (Randomized study of Efficacy and Safety in POlycythemia vera with JAK iNhibitor ruxolitinib verSus bEst available care) trial was a randomized, open-label, active-controlled phase 3 trial comparing Jakafi with BAT in 222 patients with PV. Patients enrolled in the study had been diagnosed with PV for at least 24 weeks, had an inadequate response to or were intolerant of hydroxyurea (HU), required phlebotomy for Hct control, and exhibited splenomegaly. All patients were required to demonstrate Hct control between 40% and 45% prior to randomization. After week 32, patients were able to cross over to Jakafi treatment.1,3
The composite primary end point was defined as Hct control without phlebotomy eligibility and a ≥35% spleen volume reduction as measured by computed tomography (CT) or magnetic resonance imaging (MRI). To achieve the Hct control end point, patients could not become eligible for phlebotomy between weeks 8 and 32. Phlebotomy eligibility was defined as Hct >45% that is ≥3 percentage points higher than baseline or Hct >48% (lower value).1,3
BAT included HU (60%), interferon/pegylated interferon (12%), anagrelide (7%), pipobroman (2%), lenalidomide/thalidomide (5%), and observation (15%).1,3

Complete hematologic remission with Jakafi—RESPONSE trial results

Jakafi demonstrated significantly higher rates of complete hematologic remission (CHR) vs BAT.1


BAT=best available therapy; CHR=complete hematologic remission; CI=confidence interval.
a95% CI, 16%-33%
b95% CI, 4%-15%
cA durability analysis was performed at week 80 in the original Jakafi arm.

Image that shows chart of Secondary End Point: Patients Achieving Complete Hematologic Remission at Week 32
Image that shows chart of Secondary End Point: Patients Achieving Complete Hematologic Remission at Week 32

BAT=best available therapy; CHR=complete hematologic remission; CI=confidence interval.
a95% CI, 16%-33%
b95% CI, 4%-15%
cA durability analysis was performed at week 80 in the original Jakafi arm.

Complete hematologic remission was defined as achieving hematocrit control (as specified in the primary end point), platelet count ≤400 × 109/L, and white blood cell count ≤10 × 109/L.1,3

58% of patients treated with Jakafi who achieved CHR at 32 weeks maintained this response through 80 weeks (18 months) of treatment.1

Durability of complete hematologic remission at 5 years

Durability of complete hematologic remission at 5 years

Individual Components of Complete Hematological Remission


Hematocrit control with Jakafi—RESPONSE trial results

In the RESPONSE trial, Jakafi achieved a higher rate of Hct control against BAT.1

To achieve the Hct control end point, patients could not become eligible for phlebotomy between weeks 8 and 32; phlebotomy eligibility was defined as Hct >45% that is ≥3 percentage points higher than baseline or Hct >48% (lower value).1,3

Image of chart of Hematocrit Control Component of Primary End Point at Week 32 Image of chart of Hematocrit Control Component of Primary End Point at Week 32

BAT=best available therapy; Hct=hematocrit.
aA durability analysis was performed at week 80 in the original Jakafi arm.

77% of patients treated with Jakafi who achieved hematocrit control at 32 weeks maintained this response through 80 weeks (18 months) of treatment.1

Image that says 4/5 patients …receiving BAT failed to achieve Hct control

…receiving BAT failed to achieve Hct control1

Durability of Hct control§ at 5 years
§Absence of phlebotomy eligibility.

Durability of Hct control§ at 5 years

§Absence of phlebotomy eligibility.

Individual component of complete hematologic remission

Jakafi reduced mean white blood cell (WBC) counts

In exploratory analyses from the RESPONSE trial, mean WBC counts were reduced over time for patients taking Jakafi.3

Image of chart showing Mean WBC Counts Over Time Image of chart showing Mean WBC Counts Over Time

BAT=best available therapy; WBC=white blood cell.
Patients treated with HU were included in the group of patients receiving BAT.

Image of chart showing Mean Change From Baseline in WBC Counts for Patient Subgroups With WBC Counts ≥11 x 109/L4 Image of chart showing Mean Change From Baseline in WBC Counts for Patient Subgroups With WBC Counts ≥11 x 109/L4

BAT=best available therapy; HU=hydroxyurea; WBC=white blood cell.
At baseline, 75.5% of patients (n = 83) receiving Jakafi and 71.4% of patients (n = 80) receiving BAT had WBC counts ≥11 x 109/L.4

Individual component of complete hematologic remission

Jakafi reduced mean platelet counts

In exploratory analyses from the RESPONSE trial, mean platelet counts were reduced through week 32 for patients taking Jakafi.5

Image of chart showing Mean Platelet Counts Through Week 32 Image of chart showing Mean Platelet Counts Through Week 32

BAT=best available therapy.

Image of chart showing Proportion of Patients Achieving Platelet Count ≤400 x 109/L at Week 32 Image of chart showing Proportion of Patients Achieving Platelet Count ≤400 x 109/L at Week 32

BAT=best available therapy.

Exploratory end point from the RESPONSE trial: Symptom data

  • At week 32, 49% of patients receiving Jakafi and 5% of patients receiving BAT had at least a 50% reduction in the 14-item Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) total symptom score3
  • RESPONSE was an open-label trial and, therefore, not designed to evaluate differences in symptoms

Patient-reported outcomes were assessed using the MPN-SAF symptom diary. The MPN-SAF diary was administered daily in an electronic diary format to score 14 disease-related symptoms on a scale of 0 (absent) to 10 (worst possible). At baseline, median Total Symptom Score was 23.4 (range, 0–106) in the group receiving Jakafi and 33.3 (range, 0–118) in the group receiving BAT.3,5

Image of chart showing Patients Achieving ≥50% Reduction in MPN-SAF Total Symptom Score at Week 32

Image of chart showing Patients Achieving ≥50% Reduction in MPN-SAF Total Symptom Score at Week 32

BAT=best available therapy; MPN-SAF=Myeloproliferative Neoplasm Symptom Assessment Form.
aHigher symptom score indicates greater severity of symptoms; cytokine symptom cluster (tiredness, itching, muscle aches, night sweats, and sweating while awake), hyperviscosity symptom cluster (vision problems, dizziness, concentration problems, headache, numbness or tingling in the hands or feet, ringing in the ears, and skin redness), and splenomegaly symptom cluster (abdominal discomfort and early satiety). Patients with data at baseline (value >0) and week 32 were included in this analysis.

  • Patients receiving Jakafi had greater reductions in all symptom clusters reported, whereas patients receiving BAT had an increase in scores of many symptoms3

Image of chart showing Median Percent Change in Symptom Score from Baseline to Week 32

Image of chart showing Median Percent Change in Symptom Score from Baseline to Week 32

BAT=best available therapy.
aPatients with data at baseline (value >0) and week 32 were included in this analysis. Negative values indicate a reduction in the severity of symptoms.

 Video

The Phase 3 RESPONSE|| Trial in Polycythemia Vera: Count Control and Spleen Volume Reduction in Patients With an Inadequate Response to or Intolerance of Hydroxyurea

Hematologist-oncologist Dr Gary Grad reviews the efficacy and safety of Jakafi® (ruxolitinib) in the RESPONSE|| trial, which compared Jakafi to best available therapy. Dr Grad explores relevant data on the composite primary end point of hematocrit control and spleen volume reduction, as well as effects on other blood counts, including white blood cell (WBC) count. He offers a detailed look at data from week 32 of the trial, as well as data on durability of response through week 80.

||RESPONSE=Randomized study of Efficacy and Safety in POlycythemia vera with JAK iNhibitor ruxolitinib verSus bEst available care

Image of Dr. Harry Erba

References

  1. Jakafi Prescribing Information. Wilmington, DE: Incyte Corporation.
  2. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Myeloproliferative Neoplasms V.2.2019. © National Comprehensive Cancer Network, Inc. 2018. All rights reserved. Accessed October 29, 2018. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
  3. Vannucchi AM, Kiladjian JJ, Griesshammer M, et al. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015;372(5)(suppl):1-25.
  4. Harrison C, Griesshammer M, Miller C, et al. Comprehensive haematological control with ruxolitinib in patients with polycythaemia vera resistant to or intolerant of hydroxycarbamide. Br J Haematol. 2017. doi.org/10.1111/ bjh.14764.
  5. Data on file. Incyte Corporation. Wilmington, DE.

Indications and Usage

Jakafi is indicated for treatment of polycythemia vera (PV) in adults who have had an inadequate response to or are intolerant of hydroxyurea.

Jakafi is indicated for treatment of intermediate or high‐risk myelofibrosis (MF), including primary MF, post–polycythemia vera MF and post–essential thrombocythemia MF in adults.

Jakafi is indicated for treatment of steroid‐refractory acute graft‐versus‐host disease (GVHD) in adult and pediatric patients 12 years and older.

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. Use active surveillance and prophylactic antibiotics according to clinical guidelines
  • 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 Jakafi treatment. 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
  • In myelofibrosis and polycythemia vera, the three most common nonhematologic adverse reactions (incidence >10%) were bruising, dizziness and headache. In acute graft-versus-host disease, the most common nonhematologic adverse reactions (incidence >50%) were infections and edema
  • Dose modifications may be required 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 breastfeed during treatment and for two weeks after the final dose

Please see Full Prescribing Information for Jakafi.