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ASH 2022: Rare Diseases & Blood Disorders

Evidence-Based OncologyJanuary 2023
Volume 29
Issue 1
Pages: SP42-SP46

Coverage from the 64th Annual American Society of Hematology Meeting and Exposition, December 10-13, 2022, New Orleans, Louisiana.

After a Week, Efgartigimod Lets 38% of Patients With ITP Reach Platelet Counts to Avoid Bleeding

Efgartigimod, already approved as Vyvgart to treat myasthenia gravis, allowed more than a third of patients with immune thrombocytopenia (ITP) to quickly achieve platelet levels that signal an ability to avoid sudden bleeding events, with other results of a randomized trial showing sustained responses compared with placebo.

Results of the phase 3 ADVANCE IV (NCT04188379) study were presented December 11, 2022, in a plenary session at the 64th American Society of Hematology Annual Meeting and Exposition in New Orleans, Louisiana.
Both the study’s lead author, Catherine M. Broome, MD, associate professor of medicine, Georgetown University, and Douglas B. Cines, MD, professor of medicine and pathology, University of Pennsylvania, who introduced the abstract, said patients with chronic ITP experience low platelet counts brought on by immunoglobulin G (IgG) platelet autoantibodies. IgG binds to platelets, which causes their clearance and limits their production. Besides bleeding risk, patients experience fatigue and poor quality of life, Broome said, as current therapies are linked to comorbidities and don’t work long enough.

“There is a need for better ITP therapy, which is why we embarked on this trial,” Broome said. Efgartigimod takes a new approach to blocking the effects of IgG, involving the neonatal Fc receptor (FcRn). Although its name is derived from its discovery for its ability to transport IgG from mother to fetus, Cines said, “FcRn is also widely expressed in other cell types, including endothelial cells, where it helps regulate the life span of IgG.”

As Broome explained in a news briefing before the session, “When native IgG is bound to the neonatal FC receptor, it is protected from lysosomal degradation.” Thus, disrupting the how IgG binds to FcRn would interfere with its effect on platelets. This knowledge is behind the mechanism of efgartigimod.

Study design. Broome outlined the trial’s design, which randomly assigned 131 participants 2:1 to receive 10 mg/kg of efgartigimod or placebo along with entry-level doses of background therapy, such as corticosteroids, for 24 weeks. All patients had chronic or persistent ITP; at screening, all had received at least 2 prior ITP therapies or 1 prior and 1 concurrent treatment. Patients had 2 platelet counts of less than 30 × 109/L, which Broome explained is the point at which patients can expect to avoid sudden bleeding.

During the study, all patients received treatment intravenously weekly but could switch to biweekly after week 4 if their platelet levels increased sufficiently. The primary end point was the proportion of chronic ITP patients with a sustained platelet response of ≥ 50 × 109/L in at least 4 of 6 visits between weeks 19 and 24 without intervening events, such as rescue therapy after week 12.

Key secondary end points were as follows:

  • disease control, as measured by the number of with platelets at ≥ 50 × 109/L in the chronic ITP population;
  • proportion of participants in the overall population (chronic and persistent) with sustained platelet response;
  • incidence of bleeding events; and
  • a durable, sustained platelet response, as measured by platelets at ≥ 50 × 109/L in at least 6 of 8 visits between weeks 17 and 24 in the overall population.

Results. Among the patients, the median time since diagnosis was 4.57 years and 67% had at least 3 prior treatments. Broome reported that the study met its primary end point, as sustained platelet response was achieved in more efgartigimod patients (21.8% [17/78] vs 5.0% [2/40], P = .0316).

Efgartigimod achieved all platelet-related secondary end points. The mean number of weeks of disease control was 6.1 for the group taking the study drug compared with 1.5 for placebo. This translated into 44% of the efgartigimod group achieving sustained response for at least 5 to 9 weeks compared with 12% for placebo; 28% for at least 10 to 14 weeks (0% placebo), and 17% for at least 15 to 19 weeks (0% placebo).

Sustained platelet count response was achieved by 25.6% in the efgartigimod group (22/86) compared with 6.7% for the placebo group (3/45).

Broome explained that although the group taking efgartigimod beat the placebo group on the next secondary end point—number of visits with World Health Organization bleeding score ≥ 1—it did not reach statistical significance. However, the group taking efgartigimod bested the placebo group on durable platelet count as well, 22.1% vs 6.7%.

Of note, the study drug worked quickly, with 38% of patients in the efgartigimod group achieving the < 30 × 109/L platelet level by week 1 compared with 11% of the placebo group.

In the news briefing, Broome said the drug produced no new safety signals and she noted that 90% of the patients who took part in ADVANCE IV moved forward to an open-label extension study, “which will give us an opportunity to evaluate durability of response, as well as safety.”

“Most adverse events were mild to moderate,” she said. “The results of this study showed us that we have some flexibility in dosing with both weekly and every other week administration.”

Argenx is the maker of efgartigimod.

Broome CM, McDonald V, Miyakawa Y, et al. Efficacy and safety of intravenous efgartigimod in adults with primary immune thrombocytopenia: results of a phase 3, multicenter, double-blinded, placebo-controlled, randomized clinical trial (ADVANCE-IV). Presented at: 64th American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022; New Orleans, LA. Abstract 3. https://ash.confex.com/ash/2022/webprogram/Paper167838.html

Conquering SCD by Confronting Treatment Barriers, Investigating PROs

A pair of abstracts presented during this year’s 64th American Society of Hematology Annual Meeting and Exposition explored barriers to treatment for sickle cell disease (SCD), the group of inherited blood disorders characterized by abnormal hemoglobin that cause transporting red blood cells to become hard, sticky, and C-shaped.1 SCD can lead to painful episodes or worse. Investigators explored treatment barriers that patients and their caregivers confront2 as well as patient-reported outcomes (PROs) following administration of voxelotor, approved just last year by the FDA,3 in the ongoing ActIVe trial (NCT04400487).4,5

Barriers to SCD Treatment2
“In the absence of widespread curative therapies, disease modifying therapies (DMTs) are important treatment options to manage disease complications and improve outcomes,” a team from the University of Pittsburgh wrote. However, they added, DMTs remain underutilized.

They used a behavioral theory–informed theoretical framework to assess barriers to SCD treatment across 14 domains. Their cross-sectional, web-based survey collected data on sociodemographics, DMT use, attitudes/beliefs toward DMTs, and health system–related factors. Scores were determined using a scale of 1 (strongly disagree) to 5 (strongly agree).

There were 100 patient/caregiver responses, with 54% of respondents noting they had a primary care provider (PCP) and a hematologist.

Knowledge, reinforcement, beliefs about consequences, and environmental were the 4 domains with notable findings. Eighty-five percent overall expressed worry about adverse effects.

Hydroxyurea (51%) was the most common DMT for the 63% of respondents reporting DMT use, voxelotor use was reported in an additional 13%, 64.2% reported needing more information on DMTs (vs 79.4% who said they understood them well), 30.4% had neutral beliefs (vs 63.0% who believe DMTs would lead to better outcomes), 50% of nonusers believe not enough information on DMTs is available, and 42% of current DMT users had a negative/neutral outlook on their health from using DMTs, indicating they do not “explicitly agree that their current health depends on the use of DMTs,” the investigators wrote.

Among the 91% reporting they had insurance coverage, 26% had commercial coverage and 25% had Medicaid. However, 41.1% reported limited access to health care stemming from treatment costs and 27.8% reported limited access because of insurance requirements.

“Overall, our study population may represent a subset of relatively high functioning individuals, given their enrollment in an insurance plan, access to a PCP and a hematologist, regular follow-up with a physician, and current use of a DMT,” the study researchers concluded. “Yet, our study population experiences significant barriers to DMT.”

To move forward, the authors noted that future studies need to encompass a more diverse patient population—in socioeconomic status, insurance status, and DMT use—and education initiatives need to focus more on DMT use in SCD, especially with newer promising pharmacological approaches in the pipeline.

Patient-Reported Outcomes5
Following its acquisition by Pfizer in October 2022,6 Global Blood Therapeutics (GBT) continues to make progress toward optimizing treatment for SCD. The $5.4 billion acquisition will enhance GBT’s ability to deliver life-changing treatments for historically underserved patient communities,7 while for Pfizer, GBT’s expertise in SCD, as well as its portfolio and drug development pipeline, will serve to reinforce the pharma giant’s commitment to finding effective treatments for rare hematological disorders.

The safety and efficacy of GBT’s voxelotor, a first-in-class hemoglobin polymerization inhibitor approved for use in patients 4 years and older who have SCD,7 had been demonstrated with the phase 3 HOPE8 (NCT03036813) and phase 2a HOPE-KIDS 19 (NCT02850406) trials. In the PRO analysis presented during ASH 2022, findings from the phase 4 ActIVe study were reported.4

Ten US sites administered 1500-mg daily voxelotor for up to 24 weeks, with the patient population (n = 25; 92.0% Black or African American; 64.0% female) being aged 12 to 55 years. Hemoglobin was measured at 3 follow-ups—2, 12, and 24 weeks after administration—and PROs were evaluated with the Patient Global Impression of Change (PGI-C) scale, the National Institutes of Health Patient-Reported Outcome Measurement Information System-43 (PROMIS-43) for adults (> 17 years), PROMIS-37 for adolescents (≤ 17 years), and a 10-point numeric rating scale (NRS) for pain intensity.
“A minimum response deemed meaningful was interpreted at the group level as a ≥ 5-point change from [baseline] in PROMIS domains,” the authors wrote, “and a ≥ 2-point change on the NRS.”

Even with 2 patients lost to follow-up, 78% saw their hemoglobin increase a mean (SD) 0.53 (0.839) g/dL by week 24.

By week 24, following clinician evaluation, most patients (84.6%) had an improved health status: 7.7% were “very much improved,” 46.2%, “much improved,” and 30.8%, minimally improved. At the same time point, patients self-reported improved health status (92.9%), which broke down to “very much improved” in 21.4%, “much improved” in 42.9%, and minimal improvement in 28.6%. Just 1 patient had worsened health status.

Fourteen patients provided PROMIS data at 24 weeks. Among the adults (n = 9), CFB was meaningful for fatigue (–8.3 [5.24]) and pain interference (–6.9 [5.43]). For the remaining domains of physical function (1.4 [2.14]), anxiety (–4.6 [8.48]), depression (–1.7 [6.79]), sleep disturbance (–4.3 [4.37]), ability to participate (4.5 [7.73]), and pain intensity (–1.0 [1.00]), improvements were considered modest. The pediatric patient population saw no changes that indicated meaningful improvement.

Few treatment-emergent adverse events (TEAEs) were seen, with 18 patients reporting at least 1 non–SCD-related TEAE and 3 reporting at least 1 grade 3 non-SCD-related TEAE. Diarrhea was the most common non–SCD-related TEAE reported (32.0%), and no grade 4 or higher TEAEs were seen.

“The safety profile reported in ActIVe is consistent with previous studies of voxelotor treatment,” the authors determined. “Overall, results suggest that voxelotor-treated patients may experience improvements in QOL [quality of life], including in their physical and emotional well-being.”

So, What’s Next?9
In June, GBT kicked off the next step in its investigation of GBT021 (GBT601) a next-generation hemoglobin polymerization inhibitor, among pediatric and adult patients. The phase 2 investigation (NCT05632354), part of a phase 2/3 international trial—with proposed sites in Africa, Europe, the Middle East, South America, and the United States—will focus on the investigational agent’s safety, efficacy, and tolerability.
The patient population could include up to 60 participants aged 18 to 65 years, with eligibility restricted to those with hemoglobin levels ranging from 5.5 to 10.5 g/dL and a maximum of 10 vaso-occlusive crises over the past 12 months. Randomization will be 1:1:1 for a GBT601 daily maintenance dose of 100, 150, or up to 200 mg, and the primary outcome is total patients with hemoglobin change from baseline through week 12.
Pediatric and adult outcomes will then be assessed in a phase 3 investigation once the optimal GBT601 dose is determined from the phase 2 analysis, and this portion will focus on 48-week efficacy and safety vs placebo. A third study arm will then evaluate single and multiple doses of GBT601 for pharmacokinetics and safety among pediatric patients.


1. What is sickle cell disease? CDC. Accessed December 16, 2022. https://www.cdc.gov/ncbddd/sicklecell/facts.html
2. Kazarov C, Novelli EM, Kane-Gill S, et al. Barriers to the use of disease-modifying treatments in sickle cell disease: a survey of patients and caregivers. Presented at: 64th American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022; New Orleans, LA. Abstract 2258. https://ash.confex.com/ash/2022/webprogram/Paper170881.html
3. Inserro A. Voxelotor for sickle cell disease wins FDA nod for patients as young as 4. The American Journal of Managed Care®. December 17, 2021. Accessed December 16, 2022. https://www.ajmc.com/view/voxelotor-for-sickle-cell-disease-wins-fda-nod-for-patients-as-young-as-4
4. Actigraphy improvement with voxelotor (ActIVe) study. ClinicalTrials.gov. Updated April 22, 2022. Accessed December 16, 2022. https://clinicaltrials.gov/ct2/show/NCT04400487
5. Shah N, Brown C, Andemarian B, et al. Active study: impact of voxelotor on sleep quality, physical activity, and patient-reported outcomes. Presented at: 64th American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022; New Orleans, LA. Abstract 2375. https://ash.confex.com/ash/2022/webprogram/Paper168317.html
6. Pfizer completes acquisition of Global Blood Therapeutics. News release. Pfizer. October 5, 2022. Accessed December 16, 2022. https://bit.ly/3hAW0I7
Pfizer to acquire Global Blood Therapeutics for $5.4 billion to enhance presence in rare hematology. News release. Pfizer. August 8, 2022. Accessed December 19, 2022. https://bit.ly/3G9DVdy
7. Study to evaluate the effect of voxelotor administered orally to patients with sickle cell disease (GBT_HOPE) (GBT_HOPE). ClinicalTrials.gov. Updated January 7, 2021. Accessed December 19, 2022. https://clinicaltrials.gov/ct2/show/NCT03036813
8. Study to evaluate the effect of gbt440 in pediatrics with sickle cell disease (HOPE Kids). ClinicalTrials.gov. Updated August 30, 2022. Accessed December 19, 2022. https://clinicaltrials.gov/ct2/show/NCT02850406
9. GBT initiates phase 2/3 clinical trial of GBT601 in Patients with sickle cell disease. News release. FDA. June 29, 2022. Accessed December 16, 2022. https://ir.gbt.com/news-releases/news-release-details/gbt-initiates-phase-23-clinical-trial-gbt601-patients-sickle

Analysis of Beti-Cel for Severe β-Thalassemia Shows Extensive, Long-term Patient Improvement

Patients with β-thalassemia benefited greatly after receiving a single infusion of their own altered blood-forming stem cells, betibeglogene autotemcel (beti-cel), to correct the genetic mutation causing their bodies to produce significantly inadequate levels of hemoglobin. Results from a pair of abstracts presented at this year’s 64th American Society of Hematology Annual Meeting and Exposition bear out the significant transfusion-free rate at 3 years and marked improvements in patient-reported outcomes, including the ability to work and be physically active.
The 63 patients discussed in these abstracts were enrolled in 4 consecutive studies—HGB-204 and HGB-205, a pair of phase 1/2 studies; and HGB-207 and HGB-212, both phase 3 studies. After 2 years of follow-up, patients were given the option of enrolling in the long-term follow-up study (LTF-303)1 for up to 13 years.

Currently, beti-cel is approved for use in the United States,2 but it has received only conditional marketing approval in Europe, its advancement stymied there by ongoing disagreements between bluebird bio (the sponsor of the HGB-207 study) and payment agencies that have lasted for more than 2 years after conditional marketing authorization.3

Long-term Patient-Reported Outcomes
In the original 4 studies, patient enrollment was 63.5 This long-term analysis reports outcomes from 57 patients enrolled as of August 18, 2021. The patient mix was 45.6% pediatric/adolescent patients (younger than 18 years) and 54.4% adult patients, with 22 from the original phase 1/2 studies and 35 from the phase 3 studies. The Pediatric Quality of Life Inventory (PedsQL) evaluated health-related quality of life (HRQOL) among the younger cohort, and the Short Form-36 Health Survey Physical Component Summary (SF-36 PCS), Mental Component Summary (MCS), and EuroQol (EQ-5D-3L) visual analog scale (VAS) were used for the adult cohort.

“HRQOL was assessed at baseline; months 6, 12, 18, 24 (in the parent HGB studies); and months 36, 48, and 60 (in LTF-303) after beti-cel infusion,” the authors wrote.

Noting a population norm score of 80.9, for those who achieved transfusion independence (TI), or a weighted average hemoglobin of at least 9 g/dL without packed red blood cell transfusions for 12 or more months, mean (SE) PedsQL increased 19% from baseline to month 36: from 77.4 (3.4) (n = 19) to 92.1 (4.2) (n = 4). Among the adult patient population that achieved TI—with the population norm being 50—mean scores for SF-36 PCS and MCS improved 3.5% (from 53.8 [1.4] to 55.7 [1.7]) and 10.6% (from 50.9 [1.7] to 56.3 [1.4]), respectively, over the same time period. In addition, mean EQ-5D-3L rose 3.2% (from 0.92 [0.04] to 0.95 [0.03]) and VAS, 7.3% (from 85.2 [3.0] to 91.4 [2.2]). A significant increase was seen, too, in the ability to seek employment, and physical activity improved in 80% of patients, both at month 36, while school absences decreased by close to 50%.

Long-term Outcomes After 7 Years6
Reporting outcomes from all 63 patients, this analysis also looked at data from the 4 original studies plus the follow-up, noting that patients underwent myeloablative busulfan conditioning and beti-cel infusion after hematopoietic stem and progenitor cells collection. The median (IQR) follow-up was 41.4 (9.0-87.5) months across the 5 studies, with median days to neutrophil engraftment being 23 (13-39) and to platelet engraftment, 45 (19-191).

“Peripheral blood vector copy number, levels of gene therapy–derived adult hemoglobin (HbAT87Q), and total hemoglobin were stable and durable across studies and higher in phase 3 vs phase 1/2 studies following optimized beti-cel drug product manufacturing,” the researchers wrote. “HbAT87Q levels were stabilized by month 6 and contributed to stable levels of total hemoglobin.”

As of the data cutoff in March 2021, there was a significant association seen between TI and total unsupported hemoglobin levels of 9 g/dL or higher at month 6 (P < .0001). More patients achieved TI in the phase 3 studies compared with the phase 1/2 trials, 89.5% vs 68.2%, but all patients who achieved this end point were shown to be able to maintain it as of their last follow-up. In addition, they demonstrated reduced markers of ineffective erythropoiesis and iron overload. And of the 37 patients who restarted chelation, 21 ceased it at 24 months. Meanwhile, 25% (12 of 49 patients) used phlebotomy for iron removal.

Eighteen percent of patients experienced at least 1 adverse event, with the most common related to beti-cel being abdominal pain (8%) and thrombocytopenia (5%), but nothing was seen by the 2-year postinfusion mark. Further, of the 11% who experienced veno-occlusive liver disease, treatment resolved the condition.

The best predictor of clinical outcomes, evaluated via an exploratory analysis from the phase 3 studies, was shown to be beti-cel cells transduced with the BB305 LVV (%LVV+ cells) lentiviral vector.

“The main message from our findings is that therapy to add a healthy gene to the stem cells is a valid, safe, and potentially curative treatment option for many patients with beta thalassemia,” study author Franco Locatelli, MD, professor of pediatrics at IRCCS Bambino Gesù Children’s Hospital, Catholic University of the Sacred Heart, in Rome, Italy, said in a statement.5 “Gene therapy resulted not only in sustained transfusion independence, but also in improved quality of life.”

1. Longterm follow-up of subjects with transfusion-dependent β-thalassemia treated with ex vivo gene therapy. ClinicalTrials.gov. Updated February 21, 2022. Accessed December 15, 2022. https://clinicaltrials.gov/ct2/show/NCT02633943
2. FDA approves first cell-based gene therapy to treat adult and pediatric patients with beta-thalassemia who require regular blood transfusions. News release. FDA. August 17, 2022. https://www.fda.gov/news-events/press-announcements/fda-approves-first-cell-based-gene-therapy-treat-adult-and-pediatric-patients-beta-thalassemia-who
3. Payen E. Efficacy and safety of gene therapy for β-thalassemia. N Engl J Med. 2022;386(5):488-490. doi:10.1056/NEJMe2118580
4. Locatelli F, Walters MC, Kwiatkowski JL, et al. Long-term patient-reported outcomes following treatment with betibeglogene autotemcel in patients with transfusion-dependent β-thalassemia. Presented at: 64th American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022; New Orleans, LA. Abstract 3665. https://ash.confex.com/ash/2022/webprogram/Paper163178.html
5. Research highlights cutting-edge new treatments for blood disorders. News release. American Society of Hematology. December 10, 2022. https://www.hematology.org/newsroom/press-releases/2022/research-highlights-cutting-edge-new-treatments-for-blood-disorders
6. Walters MC, Kwiatkowski JL, Porter JB, et al. Long term outcomes of 63 patients with transfusion-dependent β-thalassemia (TDT) followed up to 7 years post-treatment with betibeglogene autotemcel (beti-cel) gene therapy and exploratory analysis of predictors of successful treatment outcomes in phase 3 trials. Presented at: 64th American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022; New Orleans, LA. Abstract 2348. https://ash.confex.com/ash/2022/webprogram/Paper162400.html

Ropeginterferon Alfa-2b for PV: How Treatment, Risk Level, and Dosage Affect Outcomes

Polycythemia vera (PV) is a type of blood cancer and the most common type of chronic myeloproliferative neoplasm. PV causes too many red blood cells to be made in the bone marrow, which can trigger reactions that cause elevated numbers of white blood cells and platelets.

Although PV can be managed for many years under careful medical supervision, it can sometimes progress to a more aggressive blood disease. This includes myelofibrosis, acute myeloid leukemia, or myelodysplastic syndromes.

In 3 abstracts presented at the 64th American Society of Hematology (ASH) Annual Meeting and Exposition, researchers assessed the efficacy of ropeginterferon alfa-2b (Besremi) for treatment of PV. Ropeginterferon alfa-2b is the only FDA-approved interferon for treating PV regardless of patient risk category or treatment history.1

These abstracts compared the treatment with standard of care (SOC) and looked at differences in results between patients with low-risk and high-risk PV. The authors’ aim was to understand how a higher starting dose and quicker dose escalation affect patient outcomes.

One abstract presented the final results of the phase 2 Low-PV study (NCT03003325). This investigator-driven randomized trial compared the safety and efficacy of ropeginterferon alfa-2b vs a SOC phlebotomy-only program in patients with conventionally defined low-risk PV.2

In this trial, 100-µg doses of ropeginterferon were administered subcutaneously every 2 weeks, on top of SOC. The trial included 127 participants for up to 2 years of follow-up, with 64 in the treatment arm and 63 in the SOC arm. The composite primary end point was the percentage of patients maintaining median hematocrit (HCT) values of 45% or less over 12 months in the absence of progressive disease.

After the first year of follow-up, this primary end point was achieved in 52 (81%) patients in the ropeginterferon arm and 32 (51%) patients in the SOC arm (P < .001). Eight patients (13%) in the SOC arm experienced disease progression. This was primarily due to thrombocytosis progression with microcirculatory disturbances (n = 6), cerebral transient ischemic attack (n = 1), and splenic vein thrombosis (n = 1).

For secondary end points, the mean number of phlebotomies was 2.91 and 4.17 per patient-year in the treatment vs the SOC arm, respectively (P = .019). Zero or 1 phlebotomy was required in 30% and 16% (P = .064) of participants, and total phlebotomies were 186 and 263, respectively. Additionally, 28% and 0% of participants in the treatment and SOC arm, respectively, achieved complete hematological response (CHR).

The patients who maintained median HCT values of 45% or less continued their assigned treatment until month 24. At month 24, 83% of patients receiving ropeginterferon alfa-2b and 59% of patients receiving SOC had a complete response to treatment. This was associated with CHR in 46% and 3% of patients in the treatment and the SOC arm, respectively, whereas the number of phlebotomies was the same in both arms.

Patients who responded to ropeginterferon also had a significant decrease of JAK2 variant allele frequency (VAF) by –23%, and this decrease was seen especially in patients with initial VAF greater than 50% (–56%).

“While these results cannot prove a direct protective effect of [ropeginterferon] against thrombosis, they clearly show that it is effective on a set of potential surrogate end points that were correlated with thrombosis in the CYTO-PV study,” the authors said.

In another abstract presented at the 2022 ASH meeting, authors reported results in the ropeginterferon alfa-2b arm of the phase 3 PROUD-PV (NCT01949805) and CONTINUATION-PV (NCT02218047) trials.3 These trials demonstrated the long-term efficacy and safety of ropeginterferon alfa-2b compared with hydroxyurea/best available treatment (HU/BAT) in patients with low-risk and high-risk PV. In this pair of trials, patients with PV were randomly assigned 1:1 to receive either ropeginterferon alfa-2b or HU/BAT for 6 years or longer.

The ropeginterferon alfa-2b arm of CONTINUATION-PV included 46 patients with low-risk PV with a mean age of 50.7 years, and 49 patients with high-risk PV with a higher mean age of 63.7 years. Compared with patients with low-risk PV, those with high-risk PV had higher platelet and leukocyte counts at baseline and more frequently presented with clinically significant splenomegaly or PV-related symptoms.

Median JAK2V617F allele burden was similar in both patient groups, but patients with low-risk PV were less likely to have additional non–driver mutations. At baseline, JAK2V617F allele burden was 37.0% and 39.4% for patients with low-risk and high-risk PV, respectively, and these percentages dropped to 5.6% and 17.9% at month 72 (P < .0001).

Regardless of risk category, most patients—85.7% at low risk and 75.0% at high risk—receiving ropeginterferon alfa-2b in CONTINUATION-PV did not require any phlebotomy for the entirety of year 6. Patients with low-risk PV achieved a significantly higher CHR (73.2%) than patients with high-risk PV (38.3%) during long-term treatment at month 72, or the end of year 6 (RR, 2.41; 95% CI, 1.50-3.90; P = .0003).

Patients with low-risk PV also had a higher molecular response rate at month 72 of 84.4%, compared with 49.0% for those with high-risk PV (RR, 2.15; 95% CI, 1.37-3.37; P = .0009). This group also achieved molecular response more rapidly with a median time to first response of 12 months, compared with 18 months for the high-risk PV group.

Although these findings demonstrate that patients with different risk levels benefit from ropeginterferon alfa-2b therapy, patients with low-risk PV may have a great benefit of higher hematologic and molecular response rates.

They may also be more likely to adhere to long-term treatment.
Looking toward future studies, a third abstract outlined the methods and anticipated results of a phase 3b, single-arm, multicenter study (NCT05481151) assessing the efficacy, safety, and tolerability of ropeginterferon alfa-2b in adult patients with PV.4 Other clinical trials, including the 2 other included abstracts, confirm high CHR rates and deep molecular responses following ropeginterferon treatment. However, the study authors noted that the later dose escalation, typically ranging between 16 and 28 weeks to the highest dose, may be delaying the time to achieve CHR. In this study, the researchers aim to confirm that a higher starting dose and faster dose escalation is safe, efficacious, and supports a new optimized treatment regimen.

The researchers plan to enroll 64 adult patients with PV from the United States and Canada, including patients who are treatment naïve and who have been pretreated with HU. Patients who received previous interferon or JAK inhibitor therapy are excluded. For the first 4 weeks, patients pretreated with HU will undergo HU tapering by 25% each week.

The primary efficacy end point is CHR at week 24. This is defined as an HCT level less than 45%, white blood cell count of 10 × 109/L or less, and platelet count of 400 × 109/L or less in the absence of phlebotomy in the previous 12 weeks.

A 72-week extension will evaluate long-term safety and efficacy of ropeginterferon alfa-2b. Secondary end points include time to CHR; proportion of patients in CHR at weeks 12, 48, and 96; time to maintenance dose; and time to freedom from phlebotomies.

Ropeginterferon will be provided in 500-mcg prefilled syringes and administered subcutaneously every 2 weeks, with a starting dose of 250 mcg at day 0, 350 mcg at week 2, and a target optimal dose of 500 mcg at week 4. The authors noted that doses may be adjusted if there are concerns regarding safety or tolerability.

“We anticipate this study’s results to be in the range of the CHR response rates of the PROUD [-PV]/CONTINUATION-PV stud[ies], but in a shorter period of time,” the authors said. “It is expected that the faster and simpler dosing scheme of 250-350-500 mcg, escalated every 2 weeks, will improve treatment [adherence] and tolerance and will allow patients to achieve complete hematologic remissions significantly earlier than seen in the PROUD[-PV]/CONTINUATION-PV stud[ies].”

1. US FDA approves Besremi (ropeginterferon alfa-2b-njft) as the only interferon for adults with polycythemia vera. News release. PharmaEssentia Corporation. November 21, 2021. Accessed December 20, 2022. https://bit.ly/3HR712F
2. Barbui T, Vannucchi AM, De Stefano V, et al. Ropeginterferon alfa-2b versus standard therapy for low-risk patients with polycythemia vera: final results of low-PV randomized phase II trial. Abstract presented at: 64th American Society of Hematology Annual Meeting and Exposition, December 10-13, 2022; New Orleans, LA. Abstract 744. https://ash.confex.com/ash/2022/webprogram/Paper157255.html
3. Kiladjian JJ, Klade C, Georgiev P, et al. Efficacy and safety of long-term ropeginterferon alfa-2b treatment in patients with low-risk and high-risk polycythemia vera (PV). Abstract presented at: 64th American Society of Hematology Annual Meeting and Exposition, December 10-13, 2022; New Orleans, LA Abstract 4345. https://ash.confex.com/ash/2022/webprogram/Paper156889.html
4. Mascarenhas J, Zagrijtschuk O, Zimmerman C, Qin A, Urbanski RW. A phase 3b, single-arm, multicenter study to assess the efficacy, safety, and tolerability of ropeginterferon alfa-2b-njft (P1101) in adult patients with polycythemia vera. 64th American Society of Hematology Annual Meeting and Exposition, December 10-13, 2022; New Orleans, LA. Abstract 3004. https://ash.confex.com/ash/2022/webprogram/Paper162693.html

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