Ruxolitinib Remains an Important Clinical Tool in PV


The JAK1/JAK2 inhibitor Ruxolitinib has numerous clinical uses for the treatment of polycythemia vera, especially for adult patients who have had an inadequate response to hydroxyurea.

David Rizzieri, MD

David Rizzieri, MD

The JAK1/JAK2 inhibitor Ruxolitinib (Jakafi) has numerous clinical uses for the treatment of polycythemia vera (PV), especially for adult patients who have had an inadequate response to hydroxyurea, according to an oral presentation at the Society of Hematology Oncology 2021 Annual Meeting.

The presentation on when to intervene with ruxolitinib was given by David Rizzieri, MD, professor of Medicine at Duke University School of Medicine, a medical oncologist at the Duke Cancer institute.

During the presentation, Rizzieri discussed identifying and managing advanced PV with ruxolitinib, clinical examples, ruxolitinib efficacy in PV patients without splenomegaly, and the agent’s safety profile. 

Ruxolitinib in PV with Splenomegaly

According to National Comprehensive Cancer Network (NCCN) guidelines, many factors single a change is needed in cytoreductive therapy, for example;

- intolerance or resistance to HU2 or peginterferon alfa-2a

- disease-related symptoms

-new thrombosis or disease-related major bleeding

-progressive thrombocytosis and/or leukocytosis

-frequent and/or persistent need for phlebotomy but with poor tolerance of phlebotomy or splenomegaly

Once this occurs, NCCN guidelines suggests ruxolitinib as an option for these patients.

“The clinical experience in forming this recommendation is based primarily on the RESPONSE trial, that was the ruxolitinib versus standard therapy and phlebotomy dependent PV in patients with splenomegaly...Now let's remember the JAK/STAT pathway and the importance here. JAK1 plays a major role in signaling key pro inflammatory cytokines and JAK2 mediates signals for hematopoietic growth factors. So, any perturbations along that pathway can lead to dysregulation and progression of the hematopoietic problem,” said Rizzieri.

Ruxolitinib’s clinical efficacy in this patient population was established during the RESPONSE trial (NCT01243944).2 This phase 3 study had an actual enrollment of 222 participants and ended in February of 2018. The primary end point was the percentage of participants achieving a primary response at 32 weeks. Secondary end points included durable primary response, rate of complete remissions, duration of primary response, absence of phlebotomy eligibility, and reduction of spleen volume.

During the study, participants were randomized to receive wither ruxolitinib at a starting dose of 10 mg twice a day or best available therapy (BAT).

In total, 66% of patients in the ruxolitinib arm stayed on treatment for 5 years. The median age of patients in the experimental arm was 62 (range, 34-90) and 60 (range, 33-84) in the BAT arm. Sixty percent of patients in the experimental arm were men compared with 71% of patients in the BAT arm. Rates of HU resistance and intolerance were similar between the 2 groups. JAK2 positivity was seen in 94.5% of patients in the experimental arm compared with 95.5% of patients in the BAT arm.

Nearly a quarter, 23%, of patients who received ruxolitinib achieved hematocrit (Hct) control and ≥35% spleen volume reduction compared with just 1% of patients who received BAT (P <.0001). Patients in the experimental arm had a 74% chance of maintaining primary response at 5 years.

When the eligibility of phlebotomy was absent, 60% of patients achieved Hct control at week 32, compared to 19% of patients who received BAT. The probability of maintaining Hct control at 5 years in the experimental arm was 73%.

Twenty-four percent of patients achieved a complete hematologic remission (CHR) at week 32 compared with 8% of those who received BAT (P =.0016). The probability of maintaining CHR at year 5 for the experimental group was 55%. 

In terms of safety, during the RESPONSE trial, common any-grade AEs associated with ruxolitinib included diarrhea (15%), dizziness (15%), and dyspnea (13%). Clinically relevant laboratory abnormalities associated with ruxolitinib included anemia (72%), thrombocytopenia (27%), and neutropenia (3%). AEs lead to ruxolitinib discontinuation in 4% of patients.

Ruxolitinib in PV Without Splenomegaly

The safety and efficacy of ruxolitinib in patients with PV without splenomegaly was established in the phase 3b RESPONSE-2 trial (NCT02038036).3 This randomized, open-label, trial enrolled 149 participants. The primary end point is the rate of Hct at 28 weeks. Secondary end points include CHR, Hct at week 52 and 80, PR, rate of transformation-free survival, OS, and quality of life.

During the study, patients were randomized 1:1 to receive ruxolitinib at a starting dose of 10 mg twice a day or BAT.

Sixty-two percent of patients in the experimental arm achieved Hct at week 28, compared with 19% of patients in the BAT arm. Additionally, 23% of patients in the experimental arm achieved CHR compared to 5% of patients in the BAT arm. 

AEs were similar between RESPONSE and RESPONSE-2.

Currently, ruxolitinib has indications in PV, myelofibrosis, and in steroid-refractory acute graft versus host disease in patients 12 years and older. 

“Exploratory analyses for the white blood cell count, platelets and symptoms also seem to be encouraging for the use Jakafi. We now have the 5-year follow-up publication from last year showing the durability of these responses,” said Rizzieri. “In addition, for those without splenomegaly, we have the phase RESPONSE-2 results, which were really consistent with the pivotal RESPONSE trial. We recognize Jakafi can cause dose-related thrombocytopenia, anemia, and neutropenia.”

As parting advice for treating oncologists, Rizzieri state “Make sure you perform the white blood cell counts beforehand and monitor every 2 to 4 weeks until the patient's stable.”


Rizzieri D, Clinical Cases in Polycythemia Vera: When to Intervene With Jakafi® (ruxolitinib). Presented at the Society of Hematology Oncology 2021 Annual Meeting; September 8-10. Accessed September 9, 2021.
Study of efficacy and safety in polycythemia vera subjects who are resistant to or intolerant of hydroxyurea: JAK inhibitor INC424 (INCB018424) tablets versus best available care: (The RESPONSE Trial). Accessed September 9, 2021.
Ruxolitinib efficacy and safety in patients with HU resistant or intolerant polycythemia vera vs best available therapy. (RESPONSE-2). Accessed September 9, 2021.
Related Videos
Related Content