Allogeneic HSCT for Myelofibrosis: What to Know as More Patients Receive Treatment

Posted on June 28, 2024June 28, 2024 by MPN Advocacy & Education

June 25, 2024

Due to new transplant approaches, allogeneic hematopoietic stem cell transplant (HSCT) is now perceived as a safer therapeutic option in patients with myelofibrosis, even among older patients. Authors of a review published in the American Journal of Hematology emphasized the crucial role of early consideration and implementation of HSCT in improving clinical outcomes in this patient population.

Despite the approval of new therapies and “various other exciting non-transplant treatments in development, allogeneic HSCT remains at present the only curative therapy for patients with myelofibrosis,” wrote coauthors Haris Ali, MD, and Andrea Bacigalupo, MD.

The challenges associated with treating myelofibrosis include transplant-related mortality and the risk for relapse after HSCT. The authors aimed to provide a comprehensive review of current clinical data, new transplant platforms, and clinical updates, which can enhance patient outcomes.

“The number of patients undergoing an allogeneic HSCT annually is steadily increasing,” Dr. Ali and Dr. Bacigalupo wrote. “This reflects the fact that HSCT has become safer with the reduction in non-relapse mortality over the years, making the choice of an HSCT more attractive among hematologists caring for [patients with myeloproliferative neoplasms].”

Outcomes of the Myelofibrosis Symptom Tracking Survey

Posted on June 28, 2024June 28, 2024 by MPN Advocacy & Education

We would like to thank the 147 patients who responded to a survey that targeted how people with
Myelofibrosis tracked their symptoms and then how they used the information they gleaned from
their tracking. You’ll never guess what we found.

Nearly 65 percent of respondents said they had never tracked their symptoms. When asked why,
a piece of the MF story unfolded. Some people acknowledged that the variability of both the
symptoms and their occurrence made it difficult to track, while others felt that bringing a focus to
their MF and symptoms each day undermined their mental health. A few mentioned that they
made mental notes of their symptoms, had their various doctors tracking symptoms, or just knew
innately when something changed. Several felt that there was no reason to track their symptoms,
this may be due in part to responses to another question that revealed only around 20 percent of
individuals were encouraged by their physician to keep track of their symptoms. Of those that
did track their symptoms, most did so with their own personal pen-and-paper accounting and
used a variety of approaches using numerical scales, happy and sad faces, or a more journaling
style.

After opening this little window into the MF experience. It was hard not to have additional
questions. For example, could symptom tracking be used as both a self-care practice and a tool of
empowerment? Ultimately, the tools and techniques that are most helpful come from the insight
and strength of those who experience MF every day. If symptom tracking is not the best way to
track symptoms to possibly share with your personal health care team, or the team you work with
during a clinical trial, what does work for you? We would love to learn more, and share what we
learn to benefit others. If you have a response to these questions or anything more you would like
to say on this topic, please email us at ngiocondo@mpnadvocacy.com.

Prospective Analysis Highlights Patterns of Progression to Myelofibrosis Following Essential Thrombocythemia Diagnosis

Posted on June 19, 2024June 19, 2024 by MPN Advocacy & Education

June 17, 2024

Author(s): Caroline Seymour

Most patients with essential thrombocythemia (95.7%; 1184/1237) included in an analysis of the prospective, observational MOST study (NCT02953704) did not experience disease progression to myelofibrosis, but those who did were found to have had longer duration of disease, higher white blood cell counts, and lower hemoglobin levels at enrollment, according to findings presented at the 2024 EHA Congress.¹

Of the 4.3% (n = 53) of patients who progressed to myelofibrosis, a pathologic diagnosis of the disease or grade 2 or greater fibrosis was the most common indicator (49.1%; n = 26) of disease progression, followed by new or worsening splenomegaly coupled with a combination of high white blood cell counts and low hemoglobin levels and platelet counts (22.6%; n = 12). Additional indicators were death from myelofibrosis, myelodysplastic syndrome (MDS), or acute myeloid leukemia (AML; 11.3%; n = 6) and circulating blasts above 1% with new or worsening splenomegaly (5.7%; n = 3); patients also met at least 2 progression criteria (11.3%; n = 6).

“These findings and further analyses of MOST data will add insight into disease progression in patients with essential thrombocythemia and facilitate clinical management of this patient population,” lead study author Ruben A. Mesa, MD, FACP, president and executive director of Atrium Health Levine Cancer Institute and Atrium Health Wake Forest Baptist Comprehensive Cancer Center, and vice dean of cancer programs at Wake Forest University School of Medicine in Charlotte, North Carolina, and coauthors wrote in the poster.

Observational Study Finds Progression Common in Lower-Risk Myelofibrosis

Posted on June 19, 2024June 19, 2024 by MPN Advocacy & Education

June 14, 2024

Author(s): Sabrina Serani

Among patients with low- or intermediate-risk myelofibrosis (MF), a majority were reported to have disease progression over 4 years, and the rate of progression increased over time, according to findings from the prospective observational MOST study (NCT02953704) presented in a poster session at the 2024 EHA Congress. These findings provide important insight into the rates of disease progression for patients with lower-risk MF, a patient group with limited prospective data available on this topic.

A total of 232 patients with MF were enrolled, with 205 patients considered low or INT-1 risk due to being aged over 65 years alone comprising cohort A and 27 patients considered low or INT-1 risk for factors other than age only being evaluated in cohort B. In cohort A, 58.5% (n = 120) of patients experienced disease progression during the study, with the most common progression criteria being hemoglobin below 10 g/dL (47.5%). Further, 12 patients (10.0%) died due to disease progression and 6 (5%) had leukemic transformation. In cohort B, 29.6% (n = 8) of patients had disease progression during the course of the study.

Laboratory-defined criteria for progression in the MOST study included hemoglobin below 10 g/dL, platelet count below 100 × 109/L, less than 1% blasts, white blood cell count above 25 × 109/L, and leukemic transformation with greater than 20% blasts. Physician-reported criteria for progression were constitutional symptoms (weight loss, fever, sweats), new or worsening splenomegaly, 1 red blood cell transfusion during the study, physician-reported leukemic transformation, and death due to disease progression. The presence of at least 1 criterion was considered disease progression.

Dr Kishtagari on JAK Inhibitor Selection for Myelofibrosis in the Community Setting

Posted on June 10, 2024June 10, 2024 by MPN Advocacy & Education

June 7, 2024

John Mascarenhas, MD

John Mascarenhas, MD, professor, medicine, Icahn School of Medicine, Mount Sinai, director, Center of Excellence for Blood Cancers and Myeloid Disorders, member, The Tisch Cancer Institute, Mount Sinai, discusses phase 3 of the SENTRY (NCT04562389) trial, a global, multicenter, phase 1/3 study evaluating the efficacy and safety of selinexor (Xpovio) when given in combination with ruxolitinib (Jakafi) in patients with JAK inhibitor treatment-naive myelofibrosis.

The study is being conducted in 2 phases. In phase 1, the open-label portion of the study, enrollment has been completed and the safety and recommended dose of selinexor plus ruxolitinib was studied. Phase 1a utilized a standard 3+3 design, and phase 1b was the dose-expansion part. Phase 3 of the trial is enrolling patients with JAK inhibitor treatment-naive myelofibrosis and randomizing them 2:1 to receive the combination therapy of selinexor with ruxolitinib or placebo with ruxolitinib.

In phase 3, the primary end points are the proportion of patients with spleen volume reduction of greater than or equal to 35% at week 24, and the proportion of patients with a total symptom score reduction of greater than or equal to 50% at week 24, as measured by the myelofibrosis symptom assessment form V4.0.

Safety and efficacy of luspatercept for the treatment of anemia in patients with myelofibrosis

Posted on June 10, 2024June 10, 2024 by MPN Advocacy & Education

By: Aaron Gerds, Claire Harrison, Jean-Jacques Kiladjian, Ruben Mesa, Alessandro Vannucchi, Rami Komrokji, Prithviaj Bose, Marina Kremyanskaya, Adam Mead, Jason Gotlib, Shelonitda Rose, Fabian Sanabria, Niloufar Marsousi, Ana Giuseppi, Huijing Jiang, Jeanne Palmer , Kelly McCaul, Vincent Ribrag, Francesco Passamonti

Abstract:
The ACE-536-MF-001 trial enrolled patients with myelofibrosis (n = 95) into 4 cohorts: patients in
cohorts 1 and 3A were non-transfusion dependent (NTD) and had anemia; patients in cohorts 2 and 3B
were transfusion dependent (TD); patients in cohort 3A/3B had stable ruxolitinib treatment prior to
and during the study. All patients received luspatercept (1.0-1.75 mg/kg, 21-day cycles). Treatment
was extended if clinical benefit was observed at day 169. The primary endpoint was anemia response
rate (NTD, {greater than or equal to}1.5 g/dL hemoglobin increase from baseline; TD, transfusionindependence) over any 12-week period during the primary treatment period (weeks 1-24). Overall, 14% of patients in cohorts 1 and 3A, 10% in cohort 2, and 26% in cohort 3B met the primary
endpoint. In cohorts 1 and 3A (NTD), 27% and 50% of patients respectively had mean hemoglobin
increase {greater than or equal to}1.5 g/dL from baseline. Among TD patients, ~50% had {greater
than or equal to}50% reduction in transfusion burden. Reduction in total symptom score was observed
in all cohorts, with the greatest response rate seen in cohort 3A. Overall, 94% of patients had
{greater than or equal to}1 adverse event (AE); 47% had {greater than or equal to}1 treatmentrelated AE (TRAE; 11% grade {greater than or equal to}3), most frequently hypertension (18%),
managed with medical intervention. One patient had a serious TRAE leading to luspatercept
discontinuation. Nine patients died on treatment (unrelated to study drug). In most patients,
ruxolitinib dose and spleen size remained stable. In patients with myelofibrosis, luspatercept
improved anemia and transfusion burden across cohorts.

Pelabresib Plus Ruxolitinib Significantly Reduces Splenomegaly in Myelofibrosis

Posted on June 10, 2024June 10, 2024 by MPN Advocacy & Education

June 1, 2024

Kristi Rosa

Pelabresib (CPI-0610) plus ruxolitinib (Jakafi) significantly reduced splenomegaly, showed a trend toward a reduction in tumor symptom score (TSS) from baseline, and improved bone marrow fibrosis and anemia at week 24 compared with ruxolitinib alone in JAK inhibitor–naive patients with myelofibrosis, according to updated data from the phase 3 MANIFEST-2 study (NCT04603495) presented at the 2024 ASCO Annual Meeting.¹

As previously presented at the 2023 ASH Annual Meeting, the trial met its primary end point when a higher percentage of those who received the doublet (n = 214) experienced a 35% or greater reduction in spleen volume (SVR35) at week 24 vs those given ruxolitinib alone (n = 216), at 65.9% and 35.2%, respectively (difference, 30.4; 95% CI, 21.6-39.3; P < .001).² The mean percentage change in spleen volume at week 24 in the pelabresib/ruxolitinib arm was -50.6% (95% CI, -53.2% to -48.0%) vs -30.6% (95% CI, -33.7% to -27.5%) in the ruxolitinib-alone arm.

When looking at all responders who achieved SVR35 response, the proportion who lost response at any point in the pelabresib/ruxolitinib arm was 13.4% and more than double in the ruxolitinib-alone arm, at 27.8%. When examining the criteria of loss of SVR35 response plus a spleen volume increase greater than 25% from nadir, this occurred in 9.3% and 14.8% of patients, respectively. Notably, SVR35 response was consistently higher with the doublet vs the monotherapy across all predefined subgroups and across hematologic subgroups.

Cytopenias/Proliferation Define Outcomes for Patients With Primary MF and MF from Essential Thrombocythemia or PV

Posted on June 10, 2024June 10, 2024 by MPN Advocacy & Education

Amber Denham

05/31/2024

According to research presented at the 2024 American Society of Clinical Oncology (ASCO) annual meeting, cytopenias and/or proliferation, rather than JAK2V617F (JAK2) allele burden </≥50%, correlate with the outcomes of patients with primary myelofibrosis (PMF) and patients with MF from essential thrombocythemia or polycythemia vera (PPV/PET-MF). In addition, all patients were noted to display improved survival with ruxolitinib treatment.

Myelodepleted MF, which is characterized by cytopenias, lower JAK2 allele burden, and shorter benefit from JAK-inhibitor ruxolitinib, exhibits worse overall survival (OS) compared to myeloproliferative MF. In addition, lower JAK2 and inferior OS is generally more typical for patients with primary MF (PMF) as compared with patients with MF from essential thrombocythemia or polycythemia vera (PPV/PET-MF).

“We sought to investigate the impact of JAK2 (</≥ 50%), cytopenias and the use of ruxolitinib in outcome of PMF/PPV-PET-MF patients from our center,” explained Julie Braish, MBBCh, The University of Texas MD Anderson Cancer Center, Houston, Texas and colleagues.

To determine these results, study authors retrospectively reviewed the medical charts of 601 patients with JAK2-mutated MF (known JAK2%). Patients were divided based on the absence (-) or presence (+) of cytopenias (hemoglobin < 10 g/dL or platelets < 100 x10⁹/L) and leukocytosis (WBC ≥ 25 x10⁹/L) into: grade 1 = (-)/(-) [absence of both]; grade 2 = (-)/(+) [proliferative]; grade 3 = (+)/(-) [cytopenic]; grade 4 = (+)/(+) [cytopenic and proliferative]) and evaluated overall survival (OS) per JAK2 </≥ 50% and PMF vs PPV/PET-MF. Investigators assessed the tolerance of ruxolitinib ≥3 years by utilizing descriptive statistics, Kaplan-Meier curve with log-rank test and regression analysis for demographics, estimation of OS and its comparison.

Dr Gerds on Updated Data for Pelabresib Plus Ruxolitinib in JAK Inhibitior–Naive Myelofibrosis

Posted on June 10, 2024June 10, 2024 by MPN Advocacy & Education

Author(s): Aaron Gerds, MD

May 31, 2024

Aaron Gerds, MD, assistant professor in medicine, Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, discusses updated efficacy and safety results from the phase 3 MANIFEST-2 trial (NCT04603495) of pelabresib (CPI-0610) plusruxolitinib (Jakafi) in patients with JAK inhibitor–naive myelofibrosis.

Previously reported data from the randomized, double-blind, placebo-controlled trial, showed that the combination of pelabresib and ruxolitinib produced a statistically significant and clinically meaningful improvement in spleen volume reduction of at least 35% (SVR35) from baseline vs placebo plus ruxolitinib in patients with treatment-naive disease.

At the 2024 ASCO Annual Meeting, Gerds and colleagues reported data reaffirming these initial topline results, emphasizing their consistency over time. Among patients who achieved SVR35, 13.4% in the combination arm lost their splenic response compared with 27.8% of patients treated in the placebo arm.

Notably, the proportion of patients achieving both SVR35 and a reduction in tumor symptom score of at least 50% (TSS50) was also evaluated, Gerds states. In the combination therapy group, 40.2% of patients achieved both end points vs 18.5% with ruxolitinib alone, he reports. Gerds posits that the difference in rates of TSS50 may not be as pronounced between the combination therapy and ruxolitinib alone because single-agent ruxolitinib is highly effective in reducing symptoms; however, the higher proportion of patients achieving both end points with the combination therapy is noteworthy, he explains.

Updated MANIFEST-2 Data With Pelabresib/Ruxolitinib Support Paradigm Shift in Myelofibrosis

Posted on June 10, 2024June 10, 2024 by MPN Advocacy & Education

Author(s): Kristi Rosa

May 31, 2024

The addition of pelabresib (CPI-0610) and ruxolitinib (Jakafi) led to a significant and durable reduction in splenomegaly, showed a trend toward reduced tumor symptom score (TSS) from baseline, and improved anemia and bone marrow fibrosis at week 24 vs ruxolitinib alone in JAK inhibitor–naive patients with myelofibrosis, according to updated data from the phase 3 MANIFEST-2 study (NCT04603495) presented at the 2024 ASCO Annual Meeting.¹

A strong trend for numerical decrease in absolute change in TSS from baseline at week 24 was observed with the doublet vs the monotherapy, at -15.99 and -14.05, translating to a mean difference of -1.94 points (95% CI, -3.92 to 0.04; P = .0545). A higher proportion of patients who received the combination vs ruxolitinib alone achieved a 50% reduction in TSS (TSS50), at 52.3% vs 46.3% (difference, 6.0; 95% CI, -3.5 to 15.5; P = .216); this difference did not reach statistical significance. A two-fold increase in patients who achieved both SVR35 and TSS50 responses was observed with pelabresib plus ruxolitinib vs ruxolitinib alone, at 40.2% and 18.5%, respectively.