Momelotinib Receives FDA Approval for Myelofibrosis With Anemia

Posted on September 27, 2023September 27, 2023 by mpn_admin

Sep 15, 2023

Ariana Pelosci

The News

The FDA has approved momelotinib (Ojjaara) for the treatment of patients with intermediate- or high-risk myelofibrosis, including primary and secondary myelofibrosis, who are experiencing anemia, according to a press release from GSK.¹

The approval was based on results from the phase 3 MOMENTUM trial (NCT04173494), which was previously presented at the 2022 American Society of Clinical Oncology Annual Meeting, with other supporting data coming from a subpopulation of the phase 3 SIMPLIFY-1 trial (NCT01969838). ^2,3

Momelotinib, a once daily oral JAK1/2 inhibitor, is the only approved treatment for this indication.

Expert Perspective

“I think [momelotinib] will make an immediate impact. There clearly are individuals now who are on JAK inhibitors like ruxolitinib [Jakafi] or fedratinib [Inbrec] who have significant anemia who will immediately be potential candidates,” Ruben A. Mesa, MD, said in an interview with CancerNetwork^® prior to the approval. “We’ll see how the [National Comprehensive Cancer Network] guidelines form but there’s a case to be made for consideration [for momelotinib] as the initial JAK inhibitor selected for people who have significant anemia.”

Mesa is the president of the Enterprise Cancer Service Line and senior vice president at Atrium Health; executive director of the National Cancer Institute-designated Atrium Health Wake Forest Baptist Comprehensive Cancer Center; and vice dean for Cancer Programs at Wake Forest University School of Medicine

The MOMENTUM Trial

The MOMENTUM trial included 195 patients who were randomly assigned 2:1 to receive either momelotinib (n = 130) at 200 mg per day plus placebo or danazol (n = 65) at 600 mg per day plus placebo. At week 24 patients in the danazol arm were allowed to crossover to the momelotinib arm. The primary end point was total symptom score at week 24, and the secondary end points included transfusion independence and splenic response rate.

In the momelotinib arm, 27.7% of patients discontinued treatment for several reasons including adverse effects (AEs; n = 16), patient decision (n = 6), or death (n = 4). In the danazol arm, 41.5% of patients discontinued treatments because of AEs (n = 11), patient decision (n = 5), or death (n = 3). Additionally, 4 patients crossed over to the momelotinib arm early.

The median age in the momelotinib arm was 71.0 years vs 72.0 years in the danazol arm, 60.8% vs 67.7% were male, and 82.3% vs 76.9% were White, respectively. In terms of myelofibrosis subtype, 60.0% of those in the momelotinib arm had a primary subtype vs 70.8% in the danazol arm, 20.8% vs 16.9% had post-polycythemia vera, and 19.2% vs 12.3% had post-essential thrombocytopenia.

At week 24, the total symptom score response rate was 24.6% (95% CI, 17.49%-32.94%)in the momelotinib arm vs 9.2% (95% CI, 3.46%-19.02%) in the danazol arm (P = .0095). Moreover, 40.0% (95% CI, 31.51%-48.95%) of patients in the momelotinib arm had a 25% reduction in splenic volume vs 6.2% (95% CI, 1.70%-15.01%; P <.0001) in the danazol arm. Additionally, 35% reduction in spleen volume was observed in 23.1% (95% CI, 16.14%-31.28%) in the momelotinib arm and 3.1% (95% CI, 0.37%-10.68%; P = .0006) in the danazol arm.

At baseline, the transfusion independence rate at baseline was 13% in the momelotinib arm vs 15% in the danazol arm. Comparatively, the rate week 24 was 31% in the momelotinib arm vs 20% in the danazol arm (P = .0064).

SIMPLIFY-1 Trial

In this randomized, multicenter study, momelotinib was investigated vs ruxolitinib (Rituxan) in patients who had not received prior treatment with a JAK inhibitor. A total of 432 patients were analyzed with patients received 200 mg orally daily of momelotinib or 20 mg of ruxolitinib once per day.

A 50% of more reduction in the total symptom score was observed in 28.4% of patients receiving momelotinib vs 42.2% receiving ruxolitinib (P = .98). Momelotinib improved the transfusion rate, transfusion independence, and transfusion dependence (P ≤ .19).

Safety

In terms of safety findings from the MOMENTUM trial, the most common grade 3 or higher nonhematologic AEs included acute kidney injury (3.1% vs 9.2%), nausea (2.3% vs 3.1%), and dyspnea (2.3% vs 1.5%) in the momelotinib and danazol arms, respectively. Hematologic AEs of grade 3 or higher included anemia (60.8% vs 75.4%), thrombocytopenia (27.7% vs 26.2%), and neutropenia (12.3% vs 9.2%) in the momelotinib and danazol arms, respectively.

Grade 3 or higher AEs occurred in 53.8% vs 64.6%, and serious AEs occurred in 34.6% vs 40.0% of patients in the momelotinib and danazol arms, respectively. Investigators reported a hazard ratio (HR) of 0.734 (95% CI, 0.382-1.409; P = .3510) for overall survival overall and 0.506 up to week 24 (95% CI, 0.238-1.076; P = .0719).

Safety data from the SIMLIFY-1 trial indicated that AEs occurred in 7% of patients who received momelotinib vs 3% who received ruxolitinib. In 10% of patients, treatment-related neuropathy occurred with momelotinib treatment vs 5% with ruxolitinib.

References

Ojjaara (momelotinib) approved in the US as the first and only treatment indicated for myelofibrosis patients with anaemia, News release. GSK. September 15, 2023. September 15, 2023.
Mesa RA, Gerds AT, Vannucchi A, et al. MPN-478 MOMENTUM: phase 3 randomized study of momelotinib (MMB) versus danazol (DAN) in symptomatic and anemic myelofibrosis (MF) patients previously treated with a JAK inhibitor. J Clin Oncol. 2022;40(suppl 16):7002. doi:10.1200/JCO.2022.40.16_suppl.7002
Mesa RA, Kiladjian JJ, Catalano JV, et al. SIMPLIFY-1: A phase III randomized trial of momelotinib versus ruxolitinib in janus kinase inhibitor–naïve patients with myelofibrosis. J Clin Oncol. 2017;34(suppl 34):3844-3850. doi:10.1200/JCO.2017.73.4418

Ezobresib by Bristol-Myers Squibb for Myelofibrosis: Likelihood of Approval

Posted on September 27, 2023September 27, 2023 by mpn_admin

September 14, 2023

GlobalData tracks drug-specific phase transition and likelihood of approval scores, in addition to indication benchmarks based off 18 years of historical drug development data. Attributes of the drug, company and its clinical trials play a fundamental role in drug-specific PTSR and likelihood of approval.

Ezobresib overview

Ezobresib (BMS-986158) is under development for the treatment of solid tumors including triple-negative breast cancer, small-cell lung cancer, epithelial ovarian cancer, peritoneal cancer, renal cell carcinoma, fallopian tube cancer, Burkitt’s lymphoma/leukemia, Uveal melanoma, Uterine carcinosarcoma, NUT-midline carcinoma, Non-small cell lung cancer, metastatic hormone refractory (castration resistant, androgen-Independent) prostate cancer, blood cancer (hematologic malignancies), primary myelofibrosis (PMF), post-essential thrombocythemia (ET) or post-polycythemia vera (PV) myelofibrosis. It is administered orally as a capsule. The drug candidate acts by targeting bromodomain and extra-terminal (BET) proteins. It was under development for Ewing sarcoma.

Bristol-Myers Squibb overview

Bristol-Myers Squibb (BMS) is a specialty biopharmaceutical company that is engaged in discovery, development, licensing and manufacturing, marketing, distribution and sale of medicines and related medical products to patients with serious diseases. Its primary focus is on cancer, cardiovascular, immunology and fibrotic therapeutic projects. The company offers its products across the world to wholesalers, retail pharmacies, medical professionals, hospitals and government entities. BMS provides its products in the US, Europe, and Japan. The company conducts research to focus on the discovery and development of novel medicines that address serious diseases in areas of significant unmet medical need. BMS is headquartered in New York City, New York, the US.

Research Nurse Breaks Down Myelofibrosis-Related Anemia

Posted on September 11, 2023September 11, 2023 by mpn_admin

Sep 8, 2023

Brielle Benyon

Anemia is a common and potentially dangerous condition that can occur in patients with myelofibrosis, a type of myeloproliferative neoplasm. While anemia is a blanket term that describes low hemoglobin levels, myelofibrosis-related anemia behaves quite differently than anemia in patients with a blood cancer diagnosis, explained Sharon Bledsoe.

Bledsoe, a senior research nurse at The University of Texas MD Anderson Cancer Center in Houston, recently explained myelofibrosis-related anemia, including its cause and treatment.

CURE®: What causes anemia in patients with myelofibrosis?

Myelofibrosis is basically a disease in which the bone marrow gets replaced by connective tissue in a process called fibrosis. The bone marrow’s main objective is to produce blood cells, and in producing the blood cells — the red blood cells, the white blood cells and the platelets. When the fibrosis interferes with the production of the cells, scar tissue starts to form in the bone marrow, and the bone marrow is the soft spongy tissue in the center of the bones.

As the scar tissue starts to grow, the bone marrow loses its ability to make enough healthy blood cells. So, it produces too many abnormal blood cells. The lifespan of a true red blood cell or of a normal human red blood cell is 120 days, which is about roughly four months. When you have a patient dealing with myelofibrosis, with the scarring and all of that, they’re producing the red blood cells, but they’re not maturing; when they’re not mature, they die off faster. So, they’re producing a whole lot a whole lot, but they’re dying fast. Then you have the anemia that starts because they’re not living for enough time, so they’re not getting four months of life; within days, weeks, they’re dying off.

How is myelofibrosis-associated anemia treated?

When patients’ (hemoglobin levels) start to get low, we start to monitor their trends. We monitor their hemoglobin; we start to monitor in to see if they’re if they are going to need a transfusion. And if they need transfusions, how often are they needing the transfusions? So we’re going to monitor all of that, whether they need the transfusions and how often they need the transfusions.

That’s one way that it’s treated.

And then doctors may put them on drugs that will help the anemia, drugs like danazol and Jakafi (ruxolitinib). When those red blood cells are being produced so quickly, there’s not enough room within the bone marrow, so (they) go into the spleen, or into the liver, which is now causing them to have enlarged spleens and enlarged liver. And sometimes, because it can’t be treated, the spleen has to be removed.

(Jakafi) can take the spleen size down. However, with (Jakafi), you fall into the area where they can get skin cancers, secondary skin cancers, squamous cell carcinoma, basal cell carcinoma and things like that; you have to really, really watch for that. In treating the anemia, you have to watch for so many other things that may crop up.

What is the difference between myelofibrosis-related anemia and general anemia that is experienced in patients without an MPN?

There is a major difference, because anemia that a person would have that doesn’t have cancer presents differently than the anemia (related to MPNs). For a person who has a blood cancer, their anemia is going to come with other things (such as) possibly filling up faster (when eating), night sweats (and) extreme fatigue. And some of them have (feelings of) wanting to faint because the hemoglobin is so low.

In a person that has just routine anemia, they won’t have those types of symptoms, they’ll just probably feel a little tired or a little sluggish.

What advice do you have for patients with myelofibrosis who may be experiencing anemia?

We tell the patients to let us know if you have increased fatigue, let us know if any of your symptoms change, you have increased fatigue, you have increased night sweats, you start having fevers or things like that, let us know if any of those things are taking place. That way, I can give that information to the to the oncologist and then they know what to do for the patient.

Make sure that you are proactive as a patient, if there’s something that’s wrong, and you know that it hasn’t been an issue before, make sure that you follow up and follow through, don’t just accept (symptoms). If you have to go to 5 doctors, go to as many as it takes to get the diagnosis, because with time, time loss is not time that can be regained. So, you need to be proactive and monitor your care and know what your norms are and what’s not normal for you.

Current Approaches to Diagnose and Treat Primary Myelofibrosis

Posted on September 11, 2023September 11, 2023 by mpn_admin

Sep 7, 2023

Targeted Oncology Staff

During a Targeted Oncology™ Case-Based Roundtable™ event, Rami Komrokji, MD, discussed elements to diagnosing myelofibrosis and how to approach risk stratification before treatment.

KOMROKJI: MF could be either primary de novo or coming from secondary from essential thrombocythemia [ET] or polycythemia vera [PT]. [Concerning] the major criteria listed [by the World Health Organization (WHO)], I always bring up the 2 points that not every fibrosis in the bone marrow is myelofibrosis.¹ You can see it in lymphomas, hairy cell leukemia, connective tissue disease, etc, and you don’t need fibrosis in the early stages of myelofibrosis to make the diagnosis. The classical megakaryocytic atypia is enough and in the prefibrotic MF, that’s enough to diagnose the disease.

Prefibrotic MF is a relatively new entity that we talk about. Many patients in practice are labeled as ET, and sometimes it’s hard to tease those [differences] out. But those are the patients who we would think have ET, and in 3 to 4 years, they have overt MF. Usually, it will it take a decade to get there, but if a patient had ET and then in 3 or 4 years was in [overt] MF, those probably were patients with prefibrotic MF. There are few clues…most of the time, those patients will have high LDH [lactate dehydrogenase], on the bone marrow there will be more hypercellular granulocytic hyperplasia. There is more clustering of the megakaryocytes.

Currently, we manage them almost the same, but those are the patients who will transform earlier, at higher risk of leukemia. Maybe in the future, those are the patients we will target with some more interventions to try to prevent the overt MF.

The presence of a clonal marker excludes other diseases. [However], myelodysplastic syndrome [MDS] with fibrosis is sometimes hard to distinguish. Fibrosis can be seen in MDS; it’s typically associated with bad outcomes and the new WHO classification with the blast increase has MDS with fibrosis [as a] category on its own. In the clinical phenotype, they typically don’t have the hepatosplenomegaly as much as constitutional symptoms. They’re cytopenic, more like MDS. If a good pathologist sees myeloid or erythroid dysplasia, that will favor MDS with fibrosis. The megakaryocytes are tricky because you always see megakaryocytic atypia in MPNs [myeloproliferative neoplasms], and it depends on how experienced the hematopathologist is. If they are mistakenly calling them dysplasia, that could be deceiving. There are some minor criteria: the anemia, leukocytosis, splenomegaly, LDH, and leukoerythroblastosis.

What is the role of risk stratification when treating patients with MF?

Once we establish the diagnosis, we want to risk stratify the patients and there are many models in MF, 3 or 4 clinical and 2 molecular. I like the MIPSS70 [MIPSS70: Mutation-Enhanced International Prognostic Score System for Transplantation-Age Patients With Primary Myelofibrosis] most because it’s comprehensive and it was designed to look at the question of transplant or not in younger patients not counting the age as a factor.² Anemia, transfusion dependency, thrombocytopenia, and leukocytosis… [lead to poor prognosis]. Circulating blasts, unfavorable karyotype, [etc], all of those are weighed in these models. Molecular models…account for bad mutations like ASXL1, SRFS2, or absence of calreticulin. But at the end, we are putting the patients into a spectrum of a low-risk disease, where the survival spans many years, to a high-risk disease where the survival is less than 2 years.

Why is it important to use prognostic models for MF?

The disease risk value in practice is deciding on transplant. If somebody is not eligible for stem cell transplant [SCT], you may argue that those models are not that important. Somebody who’s very low risk will rarely be symptomatic, because if they have any symptoms, they probably move up to intermediate-1 risk.

If somebody’s survival estimate is 2 to 3 years, or an intermediate-2 or higher risk by any of those models, we think of the SCT earlier on in the course of the disease [to consider if they are] eligible for transplant by functional status and comorbidities, not necessarily by age. The second thing is [having] enough disease risk to justify the SCT. In patients who have higher risk, the timing of the transplant is probably early on. In patients with lower risk, even if they are eligible for SCT, the optimal timing is probably to try to delay the SCT. It’s always a hard decision because you don’t want to go too early [because of] upfront transplant-related mortality. But you also never want to go into an MPN accelerated phase or acute myelocytic leukemia from MPN because those diseases have terrible outcomes.

What recommendations are there for treatment of higher-risk myelofibrosis?

Once we label the patients intermediate or higher risk, we are assessing the symptoms and deciding on treatment. We rarely see patients who just [have] transfusion-dependent anemia. Those patients are probably not the classical candidates for JAK2 inhibitors, at least the classical ruxolitinib [Jakafi] or fedratinib [Inrebic].

[For] most patients…you’re treating either constitutional symptoms or splenomegaly. For those patients, JAK2 inhibitors are reasonable. The National Comprehensive Cancer Network guidelines split that choice of JAK2 inhibitor based on the platelet count.³ If it’s below 50 × 10⁹/L, pacritinib [Vonjo] is the choice; if it’s above 50 × 10⁹/L, [the choice is] ruxolitinib or fedratinib. Most [physicians] are more used to ruxolitinib, [it has] more data…but fedratinib is a reasonable option as well. Sometimes I think even a platelet cutoff of 100 × 10⁹/L would be reasonable to consider pacritinib; the platelet cutoff of 50 × 10⁹/L was for the truly unmet need and accelerated approval of pacritinib.

If patients are candidates for SCT, many times we do start the JAK2 inhibitors before the SCT because the SCT will still take 3 to 4 months to happen. If patients have a big spleen [and] poor performance from the disease, shrinking the spleen and getting them ready for SCT is reasonable.

The 3 available JAK2 inhibitors, ruxolitnib, fedratinib, and pacritinib…have different targets. Ruxolitinib targets JAK1/JAK2, [and has] potent JAK1 [activity]. Pacritinib has different targets; it doesn’t have any JAK1 activity. It has some ACVR1 [activity] so some anemia response can be explained through that [and] other inflammatory pathways like IRAK1. Fedratinib also has some FLT3 activity and some JAK1 activity. Momelotinib has JAK1 and ACVR1 activity.

The choices are based on the cytopenia profile. Fedratinib most of the time is positioned as second line after ruxolitinib in patients that are still proliferative. Ruxolitinib is the first line in patients that are proliferative, not cytopenic. Pacritinib is for thrombocytopenia and when we have approval for momelotinib, hopefully that will be for the anemia phenotype.

_References:

_{1. Barbui T, Thiele J, Gisslinger H, et al. The 2016 WHO classification and diagnostic criteria for myeloproliferative neoplasms: document summary and in-depth discussion. Blood Cancer J. 2018;8(2):15. doi:10.1038/s41408-018-0054-y}

_{2. Guglielmelli P, Lasho TL, Rotunno G, et al. MIPSS70: Mutation-Enhanced International Prognostic Score System for Transplantation-Age Patients With Primary Myelofibrosis. J Clin Oncol. 2018;36(4):310-318. doi:10.1200/JCO.2017.76.4886}

_{3. NCCN. Clinical Practice Guidelines in Oncology. Myeloproliferative neoplasms, version 2.2023. Accessed September 7, 2023. https://tinyurl.com/yw9ka77m}

Prognostic Model Could Help Predict Survival Outcomes for Patients With Myelofibrosis Undergoing AlloHCT

Posted on September 6, 2023September 6, 2023 by mpn_admin

Sep 6, 2023

Megan Hollasch

A predictive system developed using data from United States and European stem cell transplant registries was prognostic of survival in patients with myelofibrosis undergoing allogeneic hematopoietic cell transplantation.

United States patients with myelofibrosis who underwent allogeneic hematopoietic cell transplantation from an HLA-matched related/unrelated donor or unrelated HLA-mismatched donor and had data available from the Center for International Blood and Marrow Transplant Research (CIBMTR) from 2000 to 2016 were included in the study (n = 623). Then, investigators assigned a weighted score using these factors to a cohort of patients who received a transplant in Europe (European Bone Marrow Transplant [EBMT] cohort; n = 623).

Study authors created the prognostic scoring system after a Cox multivariable model was used to identify factors prognostic of mortality. An age of more than 50 years (HR, 1.39; 95% CI, 0.98-1.96) and an HLA-matched unrelated donor (HR, 1.29; 95% CI, 0.98-1.7) were associated with an increased risk of death and were each assigned 1 point. Hemoglobin levels less than 100 g/L at the time of transplantation (HR, 1.63; 95% CI, 1.2-2.19) and a mismatched unrelated donor (HR, 1.78; 95% CI, 1.25-2.52) were also found to be related to an increased risk of death, and these were each worth 2 points. Patients with 1 to 2 points were deemed to have a low score, 3 to 4 points was an intermediate score, and 5 points was a high score.

At 3 years, the overall survival (OS) rate for the CIBMTR cohort was 69% (95% CI, 61%-76%) for patients with a low score, 51% (95% CI, 46%-56.4%) for those with an intermediate score, and 34% (95% CI, 21%-49%) for those with a high score (P < .001). Using the low-risk group as reference, the intermediate-risk group had a HR of 1.64 (95% CI, 1.23-2.18), and the high-risk group had an HR of 2.65 (95% CI, 1.70-4.14; overall P = .0002).

“Increasing score was predictive of increased transplant-related mortality [TRM; P = .0017] but not of relapse [P = .12],” lead study author Roni Tamari, MD, and colleagues wrote. Tamari is an assistant attending physician and bone marrow transplant specialist at Memorial Sloan Kettering Cancer Center in New York, New York.

Additionally, the 3-category system was predictive for disease-free survival (DFS) in the intermediate-risk group (HR, 1.44; 95% CI, 1.14-1.81) and high-risk group (HR, 1.83; 95% CI, 1.24-2.71; overall P = .0015). It was also predictive for TRM in the intermediate-risk group (HR, 1.63; 95% CI, 1.10-2.44) and high-risk group (HR, 3.09 (95% CI, 1.75-5.48; overall P = .0017).

In the EBMT cohort, the 3-category system was prognostic of OS (P = .0011), DFS (P = .0007), and TRM (P = .0021), but it was not predictive of relapse (P = .1673).

The study included data from patients at least 40 years of age with myelofibrosis who underwent alloHCT. Patients were excluded if they underwent syngeneic umbilical cord blood or mismatched related-donor transplantation, had graft-versus-host disease (GVHD) prophylaxis by ex vivo T-cell depletion or CD34-positive selection procedure, or unknown GVHD prophylaxis. Additionally, those with donor data, diagnosis date, or complete 100-day follow-up data missing were excluded.

Patients in the CIBMTR and EBMT cohorts had a median age of 54 years (range, 40-75) and 52 years (range, 40-74) at diagnosis, respectively, and were mostly males (63% and 68%). Before alloHCT, Karnofsky performance status scores were between 90 and 100 in 60% and 50% of patients, respectively. At diagnosis, patients in the CIBMTR and EBMT cohorts had myelofibrosis (87% and 80%), polycythemia vera (5% and 8%), essential thrombocythemia (8% and 8%), and polycythemia vera/essential thrombocythemia (0% and 3%). Spleen status was normal (21% and 13%), splenomegaly (72% and 49%), or splenectomy (4% and 14%), and patients had received 0 (24% and 37%), 1 (41% and 20%), 2 (17% vand3%), or at least 3 (16% and 3%) prior lines of pretreatments. JAK2 mutations were present in 32% and 34% of patients, respectively, and the rates of patients who received ruxolitinib (Jakafi) were 28% and 14%, respectively.

Patients in the CIBMTR cohort had a Dynamic International Prognostic Scoring System score before alloHCT of low (12%), intermediate-1 (45%) intermediate-2 (38%), or high (2%). Cytogenetics were either normal (40%), other (18%), unfavorable (18%), or not tested (5%).

The median time from diagnosis was 18 months (range, 2-294) and 26 months (range, 2-268) in the CIBMTR and EBMT cohorts, respectively. Donors included an HLA-identical sibling (35% and 75%), well-matched unrelated donor (52% and 17%), and partially matched unrelated donor (13% and 8%). Sex matches of donor and recipient were male to male (41% and 41%), male to female (22% and 27%), female to male (22% and 17%), and female to female (15% and 15%), respectively. Additionally, patients received a graft from peripheral blood (89% and 90%), did not receive total body irradiation (84% and 85%), and received myeloablative (46% and 29%), reduced intensity (47% vs 71%), or nonmyeloablative (6% vs 0%) conditioning regimens.

At diagnosis, patients in the CIBMTR and EBMT cohorts had blast in peripheral blood of greater than 1% (14% and 17%), a hemoglobin level of greater than 100 g/L (35% and 34%), a white blood cell count greater than 25 × 109 /L (9% and 8%), a platelet count of 50 × 109 /L to 100 × 109 /L (13% and 14%), and constitutional symptoms (29% and 28%), respectively.

Before alloHCT, patients in the CIBMTR and EBMT cohorts had blast in peripheral blood of greater than 1% (30% and 32%), a hemoglobin level of greater than 100 g/L (71% and 66%), a white blood cell count greater than 25 × 109 /L (13% and 15%), a platelet count of 50 × 109 /L to 100 × 109 /L (21% and 17%), and constitutional symptoms (17% and 29%), respectively.

In the CIMBTR cohort, the 1-, 3-, and 5-year OS rates were 65.7% (95% CI, 61.9%-69.4%), 54.6% (95% CI, 50.4%-58.7%), and 49.9% (95% CI, 45.5%-54.3%), respectively. TRM rates at 1, 3, and 5 years were 20.6% (95% CI, 17.4%-23.9%), 24.7% (95% CI, 21.3%-28.3%), and 27.1% (95% CI, 23.5%-31.0%), respectively.

Additionally, the 1-, 3-, and 5-year DFS rates were 39.7% (95% CI, 35.7%-43.7%), 31.1% (95% CI, 27.3%-34.9%), and 26.5% (95% CI, 22.7%-30.5%), respectively. The relapse rates at 1, 3, and 5 years were 39.7% (95% CI, 35.8- 43.6), 44.2% (95% CI, 40.2-48.3), and 46.3% (95% CI, 42.2- 50.5), respectively.

In the EBMT cohort, the 1-, 3-, and 5-year OS rates were 68.6% (95% CI, 64.9%-72.2%), 55.0% (95% CI, 51.0%-58.9%), and 51.2% (95% CI, 47.1-55.2), respectively. The 3-year TRM rate was 27.9% (95% CI, 24.4%-31.6%), and the 3-year relapse rate was 24.3% (95% CI, 20.9%-27.8%).

Study authors noted that a limitation of the study was that it included patients treated over a long time period, and between 2000 to 2016, changes and advances were made in the field of stem cell transplantation.

“The proposed system was prognostic of survival in 2 large cohorts, CIBMTR and EBMT, and can easily be applied by clinicians consulting patients with myelofibrosis about the transplantation outcomes,” study authors concluded.

Reference

Tamari R, McLornan DP, Ahn KW, et al. A simple prognostic system in patients with myelofibrosis undergoing allogeneic stem cell transplantation: a CIBMTR/EBMT analysis. Blood Adv. 2023;7(15):3993-4002. doi:10.1182/bloodadvances.2023009886

Momelotinib Could Represent Pivotal New Treatment Option in Myelofibrosis

Posted on September 6, 2023September 6, 2023 by mpn_admin

Sep 1, 2023

Ryan Scott

Aaron T. Gerds, MD, PhD, expands on the potential role of momelotinib in the treatment of patients with myelofibrosis who present with anemia, details the data from MOMENTUM, and explains what FDA approval of momelotinib could mean for the treatment of this patient population.

The benefits in symptom burden, spleen size, and transfusion dependence demonstrated by treatment momelotinib in patients with myelofibrosis represent a potential key advance for this treatment paradigm, according to Aaron T. Gerds, MD, PhD.

A new drug application (NDA) seeking the approval of momelotinib as a potential therapeutic option in patients with myelofibrosis is currently under review by the FDA, and the review period was extended to a target action date of September 16, 2023.¹

The NDA is supported by data from the phase 3 MOMENTUM trial (NCT04173494), which evaluated the agent in patients with symptomatic and anemic myelofibrosis who received a prior JAK inhibitor. Data showed that 25% of patients treated with momelotinib (n = 130) experienced a reduction in tumor symptom score of at least 50% at week 24 compared with 9% of patients treated with danazol (n = 65; proportion difference, 16%; 95% CI, 6%-26%; P = .0095).²

Additionally, 39% of patients in the momelotinib arm achieved a spleen volume reduction of at least 25% from baseline to week 24 vs 6% in the danazol arm (P < .0001); moreover, 22% and 3% of patients, respectively, experienced a reduction of 35% or more (P = .0011). At week 24, the rates of transfusion independence were 30% (95% CI, 22%-39%) for momelotinib and 20% (95% CI, 11%-32%) for danazol (noninferiority difference, 14%; 95% CI, 2%-25%; 1-sided P = .0016).

“The potential approval of momelotinib is incredibly important for patients. Having additional agents to treat myelofibrosis would be welcomed. As little as a couple of years ago, we only had 1 approved therapy to treat myelofibrosis,” Gerds said in an interview with OncLive®. Gerds is an assistant professor in the Department of Medicine, a member of the Developmental Therapeutics Program, and medical director of the Case Comprehensive Cancer Center in Cleveland, Ohio.

In the interview, Gerds expanded on the potential role of momelotinib in the treatment of patients with myelofibrosis who present with anemia, detailed the data from MOMENTUM, and explained what FDA approval of momelotinib could mean for the treatment of this patient population. Gerds also serves as an associate professor of Medicine in the Department of Hematology and Medical Oncology at the Cleveland Clinic Taussig Cancer Institute.

OncLive: How could the potential approval of momelotinib affect current and future practice patterns for patients with myelofibrosis?

Gerds: The [potential] approval of momelotinib could be another pivotal moment in the care of patients with myelofibrosis. I would argue that the first pivotal moment was the discovery of recurrent JAK2 mutations, followed several years later by the approval of ruxolitinib [Jakafi], the first JAK inhibitor.

Momelotinib provides an extra opportunity for patients, specifically patients who have anemia along with enlarged spleens and significant symptom burden. This drug promises to try to hit all 3 of those key elements of care in patients with myelofibrosis with a single pill.

What unmet needs exist for patients with myelofibrosis and anemia?

Anemia itself in these patients is a key unmet need. Roughly 40% of patients will be anemic at the time of diagnosis. It is common diagnostic and prognostic criteria that is used to predict who may have aggressive disease. Anemia will also develop in patients within the first year after diagnosis, and at some point, every patient will develop anemia as the [bone] marrow begins to fail. Therefore, anemia is something that is incredibly common and difficult to treat.

We can give red blood cell transfusions to combat anemia, but that comes with adverse effects, such as iron overload, transfusion reactions, and the development of alloantibodies. Moreover, blood is a valuable and somewhat scarce resource. The Red Cross is constantly trying to get us to donate more blood because it is a scarce commodity, and it is also expensive to do red blood cell transfusions. In general, it’s one of the biggest costs in delivering health care for patients with hematologic malignancies. For all these reasons, treating anemia is incredibly important.

Treatments for anemia are somewhat limited. I mentioned transfusions already, and there are also erythropoiesis stimulating agents [ESAs] that can be given. Another drug, luspatercept-aamt [Reblozyl], is already approved to treat anemia in patients with myelodysplastic syndrome and beta thalassemia. It is used off-label to treat anemia in patients with myelofibrosis. danazol is also commonly used.

We already have these 3 agents; however, none of them are perfect or work 100% of the time, and there are still many patients who suffer from anemia who have [myelofibrosis]. Any new agent that is coming along that can potentially treat anemia in a different mechanism of action is always welcome.

What is the mechanism of action of momelotinib, and what prompted this agent’s examination in patients with myelofibrosis?

Momelotinib, in terms of treating anemia, works very differently than ESAs, luspatercept, and danazol. It works by inhibiting ACVR1, also known as ALK2, which is a regulator of hepcidin. Hepcidin is a key piece in what we think about in hematology in iron regulation and red blood cell production. It is a hot topic in myeloproliferative neoplasms right now, and it has been in the world of hematology for some time.

Hepcidin is a master iron regulator that helps regulate the shuttling of iron out of the iron stores, making it available for the body to use, for example, to make red blood cells. In patients with myelofibrosis, they have anemia or an inflammatory block, meaning that hepcidin levels are very high and can shut a lot of those iron stores. By lowering the levels of hepcidin by blocking ACVR1, we can restore effective erythropoiesis by dropping that anemia or inflammatory block. That component of a patient’s anemia can be reversed, potentially by this medication.

What were some of the key efficacy data from MOMENTUM?

The MOMENTUM study pitted momelotinib vs danazol, looking at a couple of key end points. The first was symptom burden reduction, and we also looked at spleen volume reduction—traditional end points for measuring response with JAK inhibitors in patients with myelofibrosis. Another key end point was transfusion independence, and that was the proportion of patients who were transfusion independent at weeks 24 and 48.

We saw that momelotinib outperformed danazol in terms of spleen volume reduction, as well as symptom burden reduction. Momelotinib was also statistically not inferior—this was a non-inferiority analysis—for transfusion independence at week 24 compared with danazol.

What does the safety profile look like for momelotinib in this population?

With respect to safety, one of the early concerns during the development of momelotinib was an increased risk of peripheral neuropathy. This was seen in some earlier studies. However, in subsequent investigations, such as the SIMPLIFY trials [NCT01969838; NCT02101268] and the MOMENTUM study, we did not see excess neuropathy in patients treated on momelotinib compared with best available therapy or danazol, respectively. The rates of peripheral neuropathy were similar in the 2 groups. That was a key take-home point in terms of safety data from the MOMENTUM study.

Certainly, some patients did develop cytopenias while on momelotinib, as well as danazol. There weren’t excess gastrointestinal toxicities, as we see with some of the other JAK inhibitors. There was no signal toward increased risk of non-melanoma skin cancers or bile reactivations. However, we certainly watch for those things whenever we’re treating a patient with a JAK inhibitor.

If it is approved, where do you see momelotinib fitting into the current treatment paradigm for this population?

With the potential approval of momelotinib, we will see what the uptake looks like in everyday practice. That will be a big part of what happens with this medication: how organically it is picked up by different oncologists and hematologists out there in the community. Clearly, it has efficacy in patients with anemia, so it would be right at home in the treatment of a patient who has myelofibrosis who needs spleen volume reduction and symptom control, and has anemia.

If we look closely at the MOMENTUM inclusion criteria, those patients did have prior exposure to a JAK inhibitor for at least one month, and they all had hemoglobin [levels] less than 10g/dL; that is where this drug tends to shine. However, the amount of JAK inhibition given to those patients prior to going on MOMENTUM was limited. We also do have up-front data in patients previously untreated [with a JAK inhibitor] from the SIMPLIFY trials. You could say that if a patient with myelofibrosis and is borderline anemic, they could also benefit from momelotinib, not just in the second line, but potentially in the frontline setting as well.

References

Verstovsek S, Gerds AT, Vannuchi AM, et al. Momelotinib versus danazol in symptomatic patients with anaemia and myelofibrosis (MOMENTUM): results from an international, double-blind, randomised, controlled, phase 3 study. Lancet. 2023;401(10373):269-280. doi:10.1016/S0140-6736(22)02036-0
GSK announces extension of FDA review period of momelotinib. News release. GlaxoSmithKline. June 16, 2023. Accessed August 31, 2023. https://www.gsk.com/en-gb/media/press-releases/gsk-announces-extension-of-fda-review-period-for-momelotinib/

Goals of Managing Cytopenic Myelofibrosis in Younger Patients

Posted on August 31, 2023August 31, 2023 by mpn_admin

Aug 29, 2023

Targeted Oncology Staff

During a Targeted Oncology™ Case-Based Roundtable™ event, Naveen Pemmaraju, MD, and participants discussed the role of JAK inhibitors in managing myelofibrosis particularly in younger patients who may receive allogeneic stem cell transplant. This is the first of 2 articles based on this event.

CASE SUMMARY

A 62-year-old man presented to his primary care physician (PCP) with symptoms of fatigue, night sweats, and increased bruising. He had a history of type 2 diabetes, hypercholesteremia, and hypertension. The PCP noticed lower hemoglobin concentration (11 to 9.5 g/dL) and platelet count (350 × 10⁹/L to 195 × 10⁹/L) from a previous annual physical examination. He was referred to a hematologist/oncologist for consultation and evaluation.

Two months post-PCP visit, he went to a hematologic oncologist. Exam findings included a spleen 5 cm below left costal margin, fatigue and night sweats worsening, bone pain, hemoglobin of 8.7 g/dL, and platelet count of 135 × 10⁹/L . He was diagnosed with primary myelofibrosis (MF); bone marrow fibrosis of grade 2, with 35% bone marrow blasts. He had a history of squamous cell carcinoma of the skin.

Molecular analysis showed a JAK2 V617F mutation and normal cytogenetics. Blood smear reveals leukoerythroblastosis: 1% blasts by manual count/flow cytometry. His ECOG performance status (PS) was 2.

DISCUSSION QUESTIONS

In your practice:
- When do you initiate therapy for a patient with MF?
- What is the importance of symptom control?
- How important is it to initiate therapy early?
- When do you start JAK inhibitor therapy?
- Do you choose your initial JAK inhibitor based on patient symptoms?

DAI CHU LUU, MD: My standpoint is that a 62-year-old is still young. I have transplant physician within 5 miles of my practice. I would definitely send to a transplant physician…see what they have to say, and then follow up on the recommendations. Usually they’ll give recommendations and then I’ll act on them. Whenever things get tough, I’ll send it to them to establish care.

NAVEEN PEMMARAJU, MD: That’s great. What do you think about JAK [Janus kinase] inhibitor therapy? [Would you use] monotherapy as standard of care up until the transplant?

LUU: Yes.

PEMMARAJU: If the platelets are below 50 × 10⁹/L, what we’ve been doing [in the past] is either giving ruxolitinib [Jakafi] or low-dose ruxolitinib. Maybe you’re doing something different. Has anyone yet prescribed the new agent, pacritinib [Vonjo], which is approved in this lower than 50 × 10⁹/L setting?

SRIKAR MALIREDDY, MD: I have prescribed pacritinib. I had a patient on ruxolitinib for the longest time and then eventually the disease progressed and I could not do any more administration of ruxolitinib. He’s been on [pacritinib] for at least 7 to 8 months.

PEMMARAJU: [Was there] any diarrhea or bleeding events? Or has it been well tolerated?

MALIREDDY: There were no [tolerability issues]. I was very careful with starting with a low dose, and then ramping up. We also watched the platelet counts, and so far…[he has] 30 × 10⁹/L to 40 × 10⁹/L platelets.

PEMMARAJU: What dose did you start? Did you start at 100 mg? Because the approved dose is 200 mg twice daily.¹

MALIREDDY: Yes, I started at 100 mg. [Since] he was tolerating it, he is at the maximum dose right now. He’s at 200 mg.

PEMMARAJU: That’s a great story. Did you have any difficulty getting it through insurance or through your specialty pharmacy?

MALIREDDY: This was one of the patients…who initially got azacitidine [Onureg] in combination with ruxolitinib. He was on a clinical trial for that.

PEMMARAJU: For the ruxolitinib/azacitidine trial [NCT01787487]?

MALIREDDY: Yes, exactly. He had some severe cytopenias, myelosuppression, and all that [on the clinical trial]. Eventually, the cytopenias progressed, then [he started on pacritinib]. I didn’t have any issues with getting approval.

PEMMARAJU: That’s great. The combined answer from both of you is the cutting-edge state of the art, which is offering a JAK inhibitor [while] trying to get to [allogeneic stem cell] transplant. We all assume—and it ends up being correct a lot of the time in our patients with myeloproliferative neoplasms as opposed to leukemia or some of the other [disease] states— what happens is [patients have an] ECOG PS of 2 to 3, but they have PS of 0 to 1 after the initiation of JAK inhibitor. With ruxolitinib, it’s usually about 3 months that you see it. After 1 week to 1 month, you start feeling great; by month 2 and 3 is the plateau.

DISCUSSION QUESTIONS

What are the therapeutic goals of therapy for a patient with aggressive disease?
When do you consider clinical trial enrollment?

PEMMARAJU: All of us in the field are thinking about the significance of cytopenic MF. It helped lead to the drug approval for this JAK inhibitor [pacritinib], which is great because I have had several similar situations in prescribing it. It’s a very well tolerated drug. But…how frequent is this? Most people in our field think that the cytopenias are treatment related or they happened later on. That is common. But thrombocytopenia and anemia can occur in a quarter or more of our patients at baseline. Some of these patients present…with fairly advanced disease. How often do you encounter a baseline platelet count of less than 50 × 10⁹/L at any point in the myelofibrosis trajectory? And before pacritinib…what were you giving these patients if you had to treat them?

JAGATHI CHALLAGALLA, MD: [I would give] low-dose ruxolitinib, or if they’re transfusion independent, just observation.

PEMMARAJU: Yes, exactly, [or] sometimes we would…give danazol or steroids. Now we know that delivering suboptimal doses is leading to suboptimal outcomes.² If you’re not reducing the spleen, not improving the symptoms, patients won’t do as well. The benefit of pacritinib…is you can give the full dose of the drug. We heard 1 story of being very cautious, but you can prescribe it as the 200 mg dosing even in the thrombocytopenic setting.1 Just watch out for diarrhea, usually resolved in the first 4 to 6 weeks. It’s usually well managed, but you and the patient need to know about it. There was some concern about cardiac bleeding events…particularly for patients on anticoagulants, but it is a fairly well-tolerated drug.

Say the patient is 82 years old, and transplant is off the table. [For] low platelet count, you’re giving a low dose of ruxolitinib, [or] you’re giving pacritinib…or fedratinib [Inrebic]. What is the goal of therapy in a patient who’s a non-transplant candidate for whom you’re giving a JAK inhibitor?

ANANTH ARJUNAN, MD: For the patient, the symptom improvement is critical. Along with that getting the spleen [size] down is important, not just for survival benefit, but for the patient to feel better. In terms of discussing treatment options, we go through the different JAK inhibitors, typically based off comorbidities, and then their [blood cell] counts. I haven’t found a reason to use fedratinib. It’s usually a question of ruxolitinib or pacritinib. For clinical trial enrollment, any time is appropriate, although we might wait until they become JAK inhibitor resistant, although you have some options recently with momelotinib.

_References:

_{1. Vonjo. Prescribing information. CTI BioPharma Corp; 2022. Accessed August 29, 2023. https://tinyurl.com/yxjnn7yu}

_{2. Maffioli M, Mora B, Ball S, et al. A prognostic model to predict survival after 6 months of ruxolitinib in patients with myelofibrosis. Blood Adv. 2022;6(6):1855-1864. doi:10.1182/bloodadvances.2021006889}

CWP-291 by JW Pharmaceutical for Thrombocythemia Myelofibrosis: Likelihood of Approval

Posted on August 31, 2023August 31, 2023 by mpn_admin

August 30, 2023

CWP-291 overview

CWP-291 (CWP-232291) is under development for the treatment of hematological tumors including relapsed or refractory acute myeloid leukemia (AML), chronic myelomonocytic leukemia-2, relapsed and refractory multiple myeloma, gastric cancer, myelofibrosis (PMF), post-polycythemia vera (PPMF), castration-resistant prostate cancer (CRPC) and post-essential thrombocythemia (PTMF). The drug candidate is administered intravenously. It acts as Sam68 inhibitor. It was also under development for the treatment solid tumors such as breast cancer, liver, lung cancer and myelodysplastic syndrome.

JW Pharmaceutical overview

JW Pharmaceutical, a subsidiary of JW Holdings Corp, is a provider of generic drugs. The company develops and markets analgesics, antipyretics and cold remedies, antidote agents, antimicrobials, anticancer agents, and others. It offers multivitamins and antianemia agents, contact lens care and ophthalmic agents, antifungal agents, cardiovascular agents, and gastrointestinal agents. JW Pharmaceutical also offers topicals, amino acid solutions, flexible IV containers, IV solutions, respiratory agents, nephrology agents, CNS, urology agents and diabetic agents. The company offers products for cardiovascular, gastrointestinal, nephrology and antianemia, anticancer and neuropsychiatry. It operates through its production and manufacturing facilities in South Korea. JW Pharmaceutical is headquartered in Seoul, South Korea.

Dr Halpern on the Investigation of Upfront Ruxolitinib and Navitoclax in Myelofibrosis

Posted on August 31, 2023August 31, 2023 by mpn_admin

Aug 28, 2023

Anna B. Halpern, MD

Anna B. Halpern, MD, physician, assistant professor, Clinical Research Division, Fred Hutch; assistant professor, hematology, University of Washington School of Medicine, discusses investigational efforts being developed to expand on the use of ruxolitinib and navitoclax in earlier treatment lines for patients with myelofibrosis.

In cohort 3 of the phase 2 REFINE trial (NCT03222609), the combination of ruxolitinib and navitoclax was evaluated in the upfront setting for patients (n=32) who had not been previously exposed to a JAK inhibitor. The study’s primary end point was spleen volume reduction of 35% or greater from baseline at week 24.

An exploratory analysis of this cohort was presented at the 2022 ASH Annual Meeting and Exposition, Halpern begins. Findings showed that navitoclax plus ruxolitinib produced a spleen volume reduction of at least 35% at week 24 across specific patient subsets, she details. These subsets consisted of patients 75 years of age or older, those with a high Dynamic International Prognostic Scoring System score, and those with HMR mutations. The percentage of patients who experienced optimal spleen volume reduction in these subgroups are 50%, 33%, and 47%, respectively.

Notably, changes in bone marrow fibrosis and reductions in the variant allele frequency (VAF) of the driver gene mutation were seen with the combination regimen in many patients, Halpern continues. Half of patients achieved a greater than 20% reduction in VAF from baseline at week 12 or 24, while a greater than 50% VAF reduction from baseline occurred in 18% of patients. When comparing those with or without HMR mutations, no differences in greater than 20% VAF reduction from baseline to week 12 or 24 were observed between populations.

These results indicate the potential disease-modifying ability of ruxolitinib and navitoclax, suggesting that reductions in bone marrow fibrosis and VAF may serve as biomarkers for disease modification, Halpern states. Notably, long-term outcomes cannot be definitively assessed as correlates for leukemia, progression, and survival, she adds. The viability of these 2 biomarker candidates should be assessed more short term, and in larger study populations, Halpern concludes.

Selinexor by Karyopharm Therapeutics for Chronic Idiopathic Myelofibrosis (Primary Myelofibrosis): Likelihood of Approval

Posted on August 28, 2023August 28, 2023 by mpn_admin

August 28, 2023

Selinexor overview

Selinexor (Xpovio, Nexpovio) is an antineoplastic agent. It is formulated as film coated tablets for oral route of administration. Xpovio in combination with dexamethasone is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody. Xpovio is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. Xpovio in combination with bortezomib and dexamethasone is indicated for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. It is also under development for the treatment of soft tissue sarcoma, osteosarcoma, leiomyosarcoma, pleomorphic liposarcoma, synovial sarcoma, epithelial ovarian cancer.

Selinexor (KPT-330) is under development for the treatment of light chain amyloidosis, anaplastic astrocytoma, diffuse intrinsic pontine glioma (DIPG), high-grade glioma (HGG), newly diagnosed advanced hepatocellular carcinoma, metastatic urothelial carcinoma, relapsed or refractory peripheral T cell lymphoma and natural killer T cell lymphomas, relapsed/refractory indolent non-Hodgkin lymphoma (R/R iHNL), malignant peripheral nerve sheath tumor (MPNST), leiomyosarcoma, endometrial stromal sarcoma, ovarian carcinoma, endometrial carcinoma, fallopian tube cancer, metastatic triple negative breast cancer, thymoma, non-small cell lung cancer, cervical carcinoma, non-Hodgkin lymphoma, melanoma, colon cancer, gastroenteropancreatic tumors, prolymphocytic leukemia, small lymphocytic lymphoma, recurrent glioblastoma, follicular lymphoma, mantle cell lymphoma, chronic lymphocytic leukemia (CLL), relapsed/refractory multiple myeloma (MM), relapsed and refractory acute myelogenous leukemia (AML), diffuse large B-cell lymphoma, chondrosarcoma, synovial sarcoma, liposarcoma, leiomyosarcoma, blast-crisis chronic myelogenous leukemia (bc-CML), relapsed and refractory acute lymphoblastic leukemia, rectal cancer, lung cancer, gynecological cancer, Penta-refractory multiple myeloma, recurrent/refractory high-grade gliomas, myelofibrosis, primary myelofibrosis, Post-Polycythemia Vera Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis (Post-ET MF), Ewing sarcoma and myelodysplastic syndrome, gastrointestinal stromal tumor (GIST), non-small cell lung cancer and recurrent glioma. The drug candidate is administered orally as a tablet and topically as a gel. It is a SINE compound that acts by targeting CRM1 (chromosome region maintenance 1 protein, exportin 1 or XPO1). It is being developed based on Selective Inhibitor of Nuclear Export (SINE) compound technology.

It was also under development for the treatment of coronavirus disease 2019 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), refractory or relapsed Richter’s transformation, metastatic castrate-resistant prostate cancer, advanced squamous cell carcinoma of head and neck, lung cancer and esophageal cancer, relapsed/refractory cutaneous T cell lymphoma, relapsed small cell lung cancer, rectal adenocarcinoma, gastric cancer, metastatic colorectal cancer and diabetic foot ulcers.

It was also under development for the treatment of recurrent glioblastoma multiforme.

Karyopharm Therapeutics overview

Karyopharm Therapeutics (Karyopharm) discovers and develops novel drugs for the treatment of cancer and other diseases. The company’s core technology harnesses the inhibition of nuclear export as a mechanism to treat patients suffering from cancer. Karyopharm’s lead product, Xpovio, is being developed for the treatment of multiple myeloma, and relapsed or refractory diffuse large B-cell lymphoma. Its pipeline drug candidates include selinexor, eltanexor, verdinexor, and KPT-9274. Karyopharm’s drug candidates are indicated for the treatment of various hematological and solid tumor malignancies including multiple myeloma, diffuse large B-cell lymphoma, liposarcoma, glioblastoma and endometrial cancer. The company has operations in the US, Israel and Germany. Karyopharm is headquartered in Newton, Massachusetts, the US.