Category Archives: Blood Cancer

Gut Microbiota Differs in Patients With MPNs

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Ashley Chan

he gut microbiota in patients with myeloproliferative neoplasms (MPNs) showed a significant difference compared with healthy controls (HCs), according to a study published in the European Journal of Haematology, although patients with MPNs who have a specific driver mutation had a similar bacterial composition compared with HCs.

In particular, MPNs, including essential thrombocythemia (ET), polycythemia vera (PV), pre-fibrotic myelofibrosis (pre-PMF) and primary myelofibrosis, have driver mutations, such as JAK2V617F, JAK2 exon, MPL or Calreticulin (CALR). Researchers found that patients with MPNs who are CALR-positive had the highest resemblance to HCs.

The study demonstrated that patients with MPNs have changes in the gut microbiota, which may be caused by their disease, which may include inflammation. This change in the microbiota has been shown to initiate and progress the disease, according to the study. Researchers also noted that the gut microbiota also affects the immune system, infection control and steady production of blood cells.

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Clinical Features and Long-Term Outcomes of a Pan-Canadian Cohort of Adolescents and Young Adults with Myeloproliferative Neoplasms: A Canadian MPN Group Study

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James T. England, Natasha Szuber, Shireen Sirhan, Tom Dunne, Sonia Cerquozzi, Madeleine Hill, Pierre J. A. Villeneuve, Jenny M. Ho, et al.

Abstract

Myeloproliferative neoplasms (MPNs) are a group of chronic hematologic malignancies that lead to morbidity and early mortality due to thrombotic complications and progression to acute leukemia. Clinical and mutational risk factors have been demonstrated to predict outcomes in patients with MPNs and are used commonly to guide therapeutic decisions, including allogenic stem cell transplant, in myelofibrosis. Adolescents and young adults (AYA, age ≤45 years) comprise less than 10% of all MPN patients and have unique clinical and therapeutic considerations. The prevalence and clinical impact of somatic mutations implicated in myeloid disease has not been extensively examined in this population. We conducted a retrospective review of patients evaluated at eight Canadian centers for MPN patients diagnosed at ≤45 years of age. In total, 609 patients were included in the study, with median overall survival of 36.8 years. Diagnosis of prefibrotic or overt PMF is associated with the lowest OS and highest risk of AP/BP transformation. Thrombotic complications (24%), including splanchnic circulation thrombosis (9%), were frequent in the cohort. Mutations in addition to those in JAK2/MPL/CALR are uncommon in the initial disease phase in our AYA population (12%); but our data indicate they may be predictive of transformation to post-ET/PV myelofibrosis.

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Hobbs Highlights Key Research in Hematologic Malignancies at the 2023 ASH Annual Meeting

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Courtney Flaherty

Ruxolitinib (Jakafi)-based combinations continue to demonstrate promising ability to address splenomegaly and a signal toward improvement of tumor-related symptoms in myelofibrosis. As novel targets for development are unearthed and considered for evaluation in combination with standard JAK inhibition, the assessment of other meaningful end points is necessary to confirm the true benefit of such agents alone or in combination across myeloproliferative neoplasms (MPNs), according to Gabriela Hobbs, MD.

Results from the phase 3 TRANSFORM-1 study (NCT04472598)were presented at the 2023 ASH Annual Meeting and demonstrated that up-front navitoclax and ruxolitinib (Jakafi) significantly reduced spleen volume by 35% or more at week 24 vs ruxolitinib plus placebo in patients with myelofibrosis.1 Despite this, no significant difference in total symptom score (TSS) was observed between the arms.

Additionally, data from the phase 3 MANIFEST-2 trial (NCT04603495) showed that pelabresib (CPI-0610) plus ruxolitinib reduced spleen volume by 35% or more in 65.9% of patients with JAK inhibitor–naive myelofibrosis vs 35.2% in those who received placebo/ruxolitinib (95% CI, 21.6-39.3; P < .001). The agent also trended toward improving TSS reduction by 50% (TSS50) at 24 weeks.2

“One of the things we must answer as a field is: What is the benefit of using combination therapy for this disease?” Hobbs, who is clinical director of the Leukemia Service at Massachusetts General Cancer Center, and an assistant in medicine at Massachusetts General Hospital in Boston, Massachusetts, stressed in an interview with OncLive®News Network: On Location during the 2023 ASH Annual Meeting. “We need to have end points that are meaningful, [as well as] therapies that are well tolerated and affordable for patients.”

In the interview, Hobbs discussed the significance of key data from the TRANSFORM-1 and MANIFEST-2 trials for patients with myelofibrosis, expanded on the ongoing or future development of novel targets and potential combination regimens across MPNs, and spotlighted the phase 1/2 SAVE study (NCT05360160) and other key research efforts being made in leukemia.

OncLive: What key data on novel ruxolitinib-based combination regimens were reported at the 2023 ASH Annual Meeting?

Hobbs: I primarily treat MPN, and this is probably the first ASH Meeting where 2 different phase 3 studies [in this space] were presented at the same time. The navitoclax data are impressive, specifically when it comes to the improvement that we see with the combination of navitoclax and ruxolitinib for improving spleen volume response [SVR]. That can be very meaningful for patients—especially those with myelofibrosis who have very large spleens. We saw a very similar SVR with the combination of pelabresib and ruxolitinib as up-front therapy in patients who had not received a JAK inhibitor before.

How do you distinguish between these 2 agents in clinical practice?

In addition to showing an impressive improvement in SVR, neither study showed a dramatic improvement in symptoms [with the combinations] compared with ruxolitinib alone. That’s something that we need to consider. Pelabresib probably did a better job at improving symptoms than navitoclax. However, we need to start thinking about whether there are more meaningful end points other than expecting agents to improve SVR and symptoms. For example, could they potentially delay progression to leukemia, improve overall survival, or improve treatment outcomes in general or after transplant? Those are difficult end points to demonstrate, so they weren’t the primary objectives of the studies.

What other emerging agents of interest were discussed during the meeting?

There were lots of interesting novel agents presented at the meeting. There is a single-agent study [examining] a selective PIM kinase inhibitor and [we saw] some updated results in approximately 30 patients who have received the agent. [The agent appears to be] incredibly well tolerated, with very little impact on blood counts in a group of heavily pretreated patients. We’re also seeing a variety of other agents that are being developed. We’re seeing results from [the phase 2 VALENTINE-PTCL01 (NCT04703192)] study with the LSD1 inhibitor valemetostat tosylate [DS-3201b], an agent that also helps to prevent the development of fibrosis.

Are any of these agents viable options for further investigation as part of combination regimens?

That is the question to answer in [the] MPN [field]. Many studies have focused on combining a novel agent with a JAK inhibitor, primarily with ruxolitinib since it’s the one that has been around for the longest. I wouldn’t be surprised if the future of myelofibrosis [will be] to utilize combinations. [However,] we must remember that there’s a difference between treating patients in clinical trials vs treating patients in real life.

At this year’s meeting, findings from the phase 1/2 SAVE study of revumenib (SNDX-5613) plus decitabine/cedazuridine, (ASTX727) and venetoclax (Venclexta) were also presented. How did the results live up to expectations surrounding the use of menin inhibitors, and what are the next steps for the regimen?

That was an exciting study [done in] a group of patients with heavily pretreated AML. Some of these patients had undergone allogeneic stem cell transplantation and had received several lines of [prior] therapy. Patients who have refractory AML must go to clinic very frequently. Being able to offer them a regimen that’s all oral is very meaningful because [they do not] have to come to clinic as frequently to receive an IV hypomethylating agent. Most patients had at least some response [to the combination], and many had impressive responses. [Notably,] many patients had been previously treated with venetoclax. Menin inhibitors have been practice-changing in AML, and we’ve seen some responses [with this approach] in patients who have previously not responded to anything else. I look forward to seeing [more about] this combination, and hopefully [we can] bring it into earlier lines of therapy.

What were the biggest updates in chronic myeloid leukemia (CML) according to data presented at the meeting?

CML is very interesting. We all think that CML is a disease that we’ve conquered. We [see] great outcomes and almost normal life expectancy in most patients who are responding to therapy. [However], there is still a lot of development in the field. Several studies are investigating asciminib [Scemblix] in several different ways. The first study that we see is the [phase 3] ASCEMBL study [NCT03106779] comparing asciminib with bosutinib [Bosulif]. Updated [data presented at this year’s meeting] showed that asciminib is still outperforming bosutinib in terms of molecular remissions. [Investigators are] also studying asciminib in different, more creative ways in CML. They’re combining asciminib with other TKIs either in the up-front setting or in a later-line setting because of its slightly different mechanism of action. We’re also seeing the development of other TKIs that are either similar to asciminib or similar to ponatinib [Iclusig] in their mechanisms of action. There is still a lot of drug development in a disease where we thankfully have [achieved] a lot of great outcomes.

[It will be interesting to see how this next generation of agents impact current practice,] especially if they improve tolerability. For a disease where [a patient has] to be on life-long therapy, it’s important to have agents that are well tolerated.

Editor’s note: This interview was conducted prior to the conclusion of the 2023 ASCO Annual Meeting.

References

  1. Pemmaraju N, Mead AJ, Somervaille T, et al. Transform-1: a randomized, double-blind, placebo-controlled, multicenter, international phase 3 study of navitoclax in combination with ruxolitinib versus ruxolitinib plus placebo in patients with untreated myelofibrosis. Blood. 2023;142(suppl 1):620. doi:10.1182/blood-2023-173509
  2. Rampal R, Grosicki S, Chraniuk D, et al. Pelabresib in combination with ruxolitinib for Janus Kinase Inhibitor treatment-naïve patients with myelofibrosis: results of the MANIFEST-2 randomized, double-blind, phase 3 study. Blood. 2023;142(suppl 1):628. doi:10.1182/blood-2023-179141

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Exploring the Molecular Aspects of Myeloproliferative Neoplasms Associated with Unusual Site Vein Thrombosis: Review of the Literature and Latest Insights

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by Erika Morsia1,2,*, Elena Torre1, Francesco Martini 2,3, Sonia Morè 1,2, Antonella Poloni 1,2, Attilio Olivieri 1,2 and Serena Rupoli 1

Abstract

Myeloproliferative neoplasms (MPNs) are the leading causes of unusual site thrombosis, affecting nearly 40% of individuals with conditions like Budd–Chiari syndrome or portal vein thrombosis. Diagnosing MPNs in these cases is challenging because common indicators, such as spleen enlargement and elevated blood cell counts, can be obscured by portal hypertension or bleeding issues. Recent advancements in diagnostic tools have enhanced the accuracy of MPN diagnosis and classification. While bone marrow biopsies remain significant diagnostic criteria, molecular markers now play a pivotal role in both diagnosis and prognosis assessment. Hence, it is essential to initiate the diagnostic process for splanchnic vein thrombosis with a JAK2 V617F mutation screening, but a comprehensive approach is necessary. A multidisciplinary strategy is vital to accurately determine the specific subtype of MPNs, recommend additional tests, and propose the most effective treatment plan. Establishing specialized care pathways for patients with splanchnic vein thrombosis and underlying MPNs is crucial to tailor management approaches that reduce the risk of hematological outcomes and hepatic complications.

Results from phase 1 of the MANIFEST clinical trial to evaluate the safety and tolerability of pelabresib in patients with myeloid malignancies

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Eytan M. Stein, Amir T. Fathi, Wael A. Harb, Gozde Colak, Andrea Fusco & James K. Mangan

 

ABSTRACT

Pelabresib (CPI-0610), a BET protein inhibitor, is in clinical development for hematologic malignancies, given its ability to target NF-κB gene expression. The MANIFEST phase 1 study assessed pelabresib in patients with acute leukemia, high-risk myelodysplastic (MDS) syndrome, or MDS/myeloproliferative neoplasms (MDS/MPNs) (NCT02158858). Forty-four patients received pelabresib orally once daily (QD) at various doses (24–400 mg capsule or 225–275 mg tablet) on cycles of 14 d on and 7 d off. The most frequent drug-related adverse events were nausea, decreased appetite, and fatigue. The maximum tolerated dose (MTD) was 225 mg tablet QD. One patient with chronic myelomonocytic leukemia (CMML) showed partial remission. In total, 25.8% of acute myeloid leukemia (AML) patients and 38.5% of high-risk MDS patients had stable disease. One AML patient and one CMML patient showed peripheral hematologic response. The favorable safety profile supports the ongoing pivotal study of pelabresib in patients with myelofibrosis using the recommended phase 2 dose of 125 mg tablet QD.

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Inherited polygenic effects on common hematological traits influence clonal selection on JAK2V617F and the development of myeloproliferative neoplasms

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Jing Guo, Klaudia Walter, Pedro M. Quiros, Muxin Gu, E. Joanna Baxter, John Danesh, Emanuele Di Angelantonio, David Roberts, Paola Guglielmelli, Claire N. Harrison, Anna L. Godfrey, Anthony R. Green, George S. Vassiliou, Dragana Vuckovic, Jyoti Nangalia & Nicole Soranzo

Nature Genetics (2024)

Abstract

Myeloproliferative neoplasms (MPNs) are chronic cancers characterized by overproduction of mature blood cells. Their causative somatic mutations, for example, JAK2V617F, are common in the population, yet only a minority of carriers develop MPN. Here we show that the inherited polygenic loci that underlie common hematological traits influence JAK2V617F clonal expansion. We identify polygenic risk scores (PGSs) for monocyte count and plateletcrit as new risk factors for JAK2V617F positivity. PGSs for several hematological traits influenced the risk of different MPN subtypes, with low PGSs for two platelet traits also showing protective effects in JAK2V617F carriers, making them two to three times less likely to have essential thrombocythemia than carriers with high PGSs. We observed that extreme hematological PGSs may contribute to an MPN diagnosis in the absence of somatic driver mutations. Our study showcases how polygenic backgrounds underlying common hematological traits influence both clonal selection on somatic mutations and the subsequent phenotype of cancer.

Main

Myeloproliferative neoplasms (MPNs) are rare chronic hematological cancers characterized by the overproduction of mature blood cells leading to elevated blood cell parameters. They are typically driven by somatically mutated JAK2-mediated, calreticulin (CALR)-mediated or MPL-mediated clonal expansion1. JAK2 mutations are found in both polycythemia vera (PV) and essential thrombocythemia (ET), which are distinct but overlapping MPNs characterized by increased numbers of red blood cells and platelets, respectively. Mutant JAK2 is commonly detectable in 0.1–3% of the healthy population as clonal hematopoiesis (CH)2,3,4,5,6,7, with the vast majority of carriers not meeting or going on to develop disease-defining characteristics of MPN. Little is understood about why only a minority of individuals with mutated JAK2 develop more severe hematological manifestations of MPN and the factors that influence blood count heterogeneity in MPNs.

The 46/1 haplotype near JAK2 is a known germline risk factor for MPNs in the population8. Genome-wide association studies (GWAS) have identified additional disease-associated germline risk loci, estimating the liability-scale heritability of MPNs based on common single-nucleotide polymorphisms (SNPs) to be ~6.5% (refs. 9,10,11). However, these germline risk loci insufficiently explain the phenotypic heterogeneity observed within MPNs and in JAK2-mutated healthy carriers.

Blood cell traits vary widely in the healthy population. The genetic architecture underlying these traits is highly polygenic, with more than 11,000 independently associated genetic variants discovered so far12,13,14. These genome-wide associated variants, when combined in polygenic scores (PGSs), explain a large proportion of phenotypic variance among healthy individuals (from 2.5% for basophil count to 27.3% for mean platelet volume) and are associated with multiple common diseases and rare hematological disorders14. We hypothesized that a genetic burden of germline variants associated with extreme hematological traits could influence phenotypic heterogeneity in association with mutated JAK2, by influencing the clonal dynamics of mutant JAK2 and/or modifying its downstream consequences. In this study, we integrate information on somatic driver mutations, germline genetic variants associated with MPNs, and CH and hematological trait PGSs to study how inherited polygenic variation underlying blood cell traits influences clonal selection on mutated JAK2 and MPN disease phenotypes (Supplementary Fig. 1).

Results

Inherited polygenic contribution to JAK2 V617F positivity

One in 30 healthy individuals reportedly harbors JAK2V617F in their blood, as determined using sensitive assays6. The majority of such individuals have low levels of JAK2V617F and do not meet clinical criteria for MPN due to the absence of elevated blood cell parameters. We wished to understand whether inherited polygenic loci that underlie blood cell traits influence the strength of clonal selection on JAK2V617F.

We studied the germline characteristics of individuals in UK Biobank (UKBB) with and without JAK2V617F. From 162,534 genetically unrelated individuals of European ancestry within the UKBB whole-exome sequencing cohort (‘200k UKBB-WES cohort’; Methods), we identified 540 individuals with one or more mutant reads for JAK2V617F (0.3%, median variant allele frequency (VAF) = 0.056, range = 0.019–1; Supplementary Fig. 2; ‘UKBB-JAK2V617F cohort’). The lower rate of JAK2V617F in the UKBB-WES cohort compared to other population studies6,7 could be explained by its low sequencing coverage (21.5× depth), as also reported previously15 (Supplementary Fig. 3). As expected, there was some overlap among individuals with JAK2V617F and those with a diagnosis of MPN. Of the 423 individuals labeled with a diagnosis of MPN (156 with ET, 161 with PV and 106 with myelofibrosis (MF)), 72 were positive for JAK2V617F (Supplementary Table 1).

We built PGSs for 29 blood cell traits covering a wide range of hematopoietic parameters (Supplementary Table 2). Blood cell trait-specific PGSs were then weighted (by effect size) by the sum of all common (minor allele frequency (MAF) > 0.01) variants that were independently associated with a blood cell trait at genome-wide significance (P < 5 × 10−8) in UKBB (Methods)14. To assess the association between hematological PGSs and small (VAF < 0.1, n = 397) or large (VAF ≥ 0.1, n = 143) JAK2V617F clones, we used multinomial logistic regression including PGSs for each hematological trait (units of s.d.), together with previously reported germline sites associated with MPN9 and CH16 (PGSMPN and PGSCH) as covariates. To account for the recognized predisposition risk for MPN driven by the JAK2 46/1 haplotype8, we computed two PGSMPN scores, separating rs1327494 (tagging the JAK2 46/1 haplotype; PGSMPN–46/1) from nontagging JAK2 variants (PGSMPN-other). We found a negative association between the PGSs for both mean reticulocyte volume (PGSMRV) and immature reticulocyte fraction (PGSIRF) and small JAK2V617F clones (P = 6.2 × 10−4 and 0.0018, false discovery rate (FDR) < 0.05; Supplementary Table 3). We also found significant positive associations with small JAK2V617F clones for the PGSs of plateletcrit (PGSPCT) and monocyte count (PGSMONO) (P = 9.5 × 10−4 and 0.0036, FDR < 0.05). Germline predisposition to high MONO and PCT values was also positively associated with large JAK2V617F clones at modest significance (P = 0.033 and 0.0022, FDR-adjusted P = 0.31 and 0.064; Fig. 1a). Repeating the analysis above excluding MPN cases still demonstrated a significant association between PGSPCT or PGSMONO and small JAK2V617F clones (P < 0.013, Bonferroni corrected; Supplementary Table 4), suggesting that the inherited effects on JAK2V617F were not driven by the subset of MPN cases. These associations were independent of the known germline risk loci associated with MPN and CH (Supplementary Table 3). Validating these associations in the full UKBB-WES dataset (n = 799 and 326 for small and large clones, respectively, and n = 338,919 for controls), we again replicated the associations between PGSPCT and small JAK2V617F clones and between PGSMONO and large JAK2V617F clones at FDR < 0.05 (PCT: odds ratio (OR) = 1.15 (change in odds per increase of 1 s.d. in PGS), 95% confidence interval (CI) = 1.07–1.24, P = 1.4 × 10−4; MONO: OR = 1.20, 95% CI = 1.07–1.34, P = 0.0014; Supplementary Table 5).

Data are presented as ORs (solid dots) with 95% CIs (error bars). a, PGSs with significant associations with small clone size of JAK2V617F (FDR < 0.05) compared to the CH and MPN PGSs (Supplementary Table 3). OR was defined as the change in odds per increase of 1 s.d. in PGS. b, Causal effects estimated by four MR methods for the exposure traits whose PGSs were found to have significant predisposition risk for JAK2V617F positivity (Supplementary Table 7). OR was defined as the change in odds per increase of 1 s.d. in exposure. The MR results shown were based on GWAS summary statistics for JAK2V617F positivity in the full UKBB (Supplementary Fig. 4). Results based on the main discovery set (200k UKBB-WES cohort) are shown in Supplementary Table 6. The MR result for MRV was not available due to a lack of corresponding GWAS summary data in INTERVAL.

To understand the causal relationship among these associations, we undertook Mendelian randomization (MR) analyses with GWAS estimates for the exposure (blood traits) and the outcome (JAK2V617F positivity; Supplementary Fig. 4) obtained from two independent sources. We used genetic instruments for hematological traits identified from UKBB, with effect size estimates from INTERVAL17 (n = 30,305), an external independent cohort. MRV was excluded due to a lack of data in INTERVAL. Both PCT and MONO showed significant causality on the presence of a JAK2V617F clone based on inverse variance-weighted (IVW)18 MR and demonstrated consistent effect estimates using two other MR methods (simple median and weighted median), suggesting that higher MONO and higher PCT values cause a detectable JAK2V617F clone (Supplementary Table 6).

Extending this analysis to the full UKBB-WES cohort (JAK2V617F, n = 1,125; controls, n = 338,919) validated these causal associations with greater estimation accuracy (PCT: ORIVW = 1.52, 95% CI = 1.29–1.78, P = 3.0 × 10−7; MONO: ORIVW = 1.3, 95% CI = 1.15–1.49, P = 4.6 × 10−5; Fig. 1b and Supplementary Table 7). The IVW method of MR (Methods) assumes that the germline loci that drive MONO and PCT have no direct causal effect on driving a JAK2V617F clone (that is, there are no direct causal effects of the genetic instruments on the outcome). We found no evidence of pleiotropy using the MR-Egger19 test; the estimated intercept was not significantly different from zero with P = 0.84 and P = 0.90 for PCT and MONO, respectively. The causal relationship was also significant for PCT and MONO (P < 0.05; Supplementary Table 7 and Supplementary Fig. 5). Additionally, the estimates were not biased by any potential pleiotropic outlier variants and were highly consistent with outlier-corrected causal estimates (Supplementary Table 7 and Methods). Lastly, to ensure the results were not confounded by the possibility that the genetic loci used as instruments for MR directly promoted the outcome (that is, JAK2V617F positivity), we repeated the analysis excluding genetic instruments associated with JAK2V617F positivity (Passociation < 10−6), as well as those that correlated with JAK2V617F variants (that is, those variants and JAK2V617F variants are in linkage disequilibrium (LD) r2 > 0.01) or were in proximity to JAK2V617F variants (in the 10-Mb region centered on each variant), and found no major changes (Supplementary Table 8). Importantly, any reverse causal effect we detected for MONO and PCT was subtle and with pleiotropic effects (PEgger > 0.05 and PEgger-intercept < 0.05; Supplementary Table 9 and Supplementary Fig. 6).

Overall, the association results combined with MR suggest that higher PCT and MONO are causal for the presence of a JAK2V617F clone. This would also explain why individuals with germline predisposition to high PCT and MONO are also more likely to harbor a JAK2V617F clone. Given that acquisition of somatic mutations in blood is largely stochastic in healthy populations20, our data suggest that genetically predicted PCT and MONO influence clonal selection on nascent JAK2V617F cells to promote mutation acquisition.

Germline contribution to blood cell count variation in MPNs

Having shown that polygenic germline loci can predispose to JAK2 clone positivity through their influence on blood cell trait levels, we next studied the contribution of these inherited sites to clinical phenotypes of MPN. We first considered the four blood cell traits that are used to define MPN subcategories clinically21 as follows: hemoglobin concentration (HGB) (g dl–1 divided by 10), hematocrit (HCT) (%), platelet count (PLT) (×109 divided by 1,000) and white blood cell count (WBC) (×109 divided by 100). We used SNP arrays to measure genome-wide polymorphism in an MPN cohort of 761 patients (PV, n = 112; ET, n = 581; MF, n = 68), in whom diagnostic blood cell counts were available and mutation status for a panel of cancer-associated genes (Fig. 2a) had previously been characterized22.

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Patients With MPNs Face a Heighted Risk for Thrombotic, Cardiovascular Events

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Alex Biese
Patients with myeloproliferative neoplasms (MPNs) — a group of blood cancers that causes the bone marrow to overproduce red or white blood cells or platelets (including polycythemia vera, essential thrombocythemia and myelofibrosis) — face a height risk for thrombotic and cardiovascular events.

But Kim Noonan, DNP, ANP-BC, AOCN, FAAN, Nursing and Patient Care Services Chief Nurse Practitioner at the Dana-Farber Cancer Institute in Boston, said there are things nurses can do to help manage that risk, such as inquiring about patients’ history of blood clots and encouraging patients to not be sedentary, as well as watching for symptoms such as elevated heart rate and shortness of breath.

“I am always thinking about thrombosis first, and then I can relax if I have maybe another explanation for their shortness of breath,” Noonan said. “But we’re always working it up, we really do due diligence to not miss some kind of thrombotic event that’s going on.”

Noonan spoke with Oncology Nursing News about awareness of the potential for thrombotic and cardiovascular events, risk factors to be mindful of and everyday actions patients can take to lower their risk.

Transcript:

Noonan: NCCN, the National Comprehensive Cancer Network, really has done a lot of work in identifying this for multiple myeloma patients, and they actually have come up with guidelines as to who really needs to be on anticoagulant therapy and who does not, and they’ve identified factors that we need to consider. And so, I think it’s getting a lot of press, it’s getting a lot of attention, certainly in the myeloma world. But I think it deserves a little bit more attention, I hate to say it, but maybe in solid tumor worlds as well.

One of the things that I didn’t mention was that, I think I said people that are dehydrated are at risk, but also people that have been on like airplane rides, people that have been in long car rides, too, are really at risk. So those are other risk factors that I think I failed to mention.

Oncology Nursing News: Would working a sedentary job, such as a desk job, also potentially be a risk factor as well?

Noonan: That’s a huge risk factor, as well, to the point of, we say to people, if you’re not getting up and walking around, maybe we should consider putting you on anticoagulation therapy right up front as opposed to just using an aspirin.

Oncology Nursing News: What are some simple things, such as getting up and walking around, that folks can do in their everyday lives to lower their risk?

Noonan: Yeah, that’s a really good question. We really want people to stay hydrated. We want them to get up and walk around. We want them to be aware of what the symptoms are, they can be doing everything right and still develop a clot because of the medication that they’re on.

But I think also, education is essential, that you are on a medication that can increase your chances of developing a clot or thrombosis, and just be aware of what the symptoms are.

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A Patients Speaks Out About Her Experience With MPN Symptoms

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Darlene Dobkowski, MA

Fatigue, pain, and itchiness are often some of the most troublesome symptoms patients with a myeloproliferative neoplasm (MPN) faces, according to Jessica Kuhns.

Kuhns, a 42-year-old woman with an MPN, spoke with Oncology Nursing News about receiving her diagnosis in 2016 and how nurses have helped her manage her symptoms. Despite a high turnover rate of nurses, she appreciates their collective efforts.

Oncology Nursing News: Tell me about yourself.

Kuhns: My name is Jessica Kuhns. I’m 42 years old. My biggest accomplishment is my son Jaden. We’re kind of a tag team. Everything I do, he’s right there with me. Whatever he does, I do with him. In 2016, I was diagnosed with MPN. I’ve been fighting it ever since and doing the best I can day by day.

Can you tell us about when you were diagnosed?

It all started with a magnetic resonance imaging [MRI] test on my knee, believe it or not. TIn the MRI, they saw that my spleen was severely enlarged. They wanted me to go to a hematologist. I started seeing a doctor in Pennsylvania, where I live. I had just had a hysterectomy. I had just beaten uterine cancer in 2015. And she had assured me the doctor that, after the hysterectomy and a splenectomy that my iron levels — because I had very low iron as well —would go back to normal. It would be a better thing for me to have my spleen removed. So I said OK.

I went and I had the procedure. They actually screwed it up really bad and I darn near died. They started out laparoscopically, but they cut out a major artery and I started bleeding out. Then I developed a massive, massive blood clot that consumed 3 major return veins from my intestines. The doctors had told my husband, at that time, and my son to start making my final arrangements, and that they didn’t see me walking out of the hospital.

I was then introduced to my now-doctor, and he came in like a wrecking ball. He was like, I’m your doctor, and I think I have an idea of what’s going on. As long as you’re willing to fight, I’m going to fight with you. And we have. He got me out of the hospital. My platelets were at 1.9 million. He got them under control, and back down to a “normal range.” I was able to leave the hospital and I’ve been great since.

You mentioned some side effects that you encountered since you were diagnosed. Were there any other ones outside of the surgical procedure that you’ve experienced?

Yeah, there are definitely side effects from this disease. The 3 top complaints, which are my 3 top complaints, are fatigue, pain, and itchiness. Those are the three that I most complain of. Mine are definitely pain, fatigue, and I do get itchy, but I don’t know if it’s because of the changing of the seasons or if it’s from the MPN. I hate to blame everything on MPN.

How have nurses helped you address those side effects and to potentially manage them?

They have absolutely directed me in the right way, as far as finding resources, and what will help and what makes it worse. They’ve done a great job in guiding me to find the information that I needed.

Is there a certain moment that stands out to you when a nurse has helped you?

Not one that stands out too much. I mean, unfortunately, such a high turn rate of nurses, it’s really sad. So I can’t say that I’ve had one specific nurse or one specific instance that I was like, Oh, wow, this is amazing. But I have had moments where my nurses did amazing things for me.

Was there ever advice that a nurse may have given you that really helped you?

They just always encouraged me to stay as positive as I can. I know it sounds corny, but the more positive you stay, the better chances you have of fighting this. They encourage you to keep going because there are times where like, oh, this is just so frustrating. And they’re just right there pushing you along, like you got this.

What advice would you give to both patients and nurses?

I think the nurses are doing great listening to us, I don’t think that’s the problem. Unfortunately, like I said, with such a high turn rate, you don’t see the same nurse repeatedly. Every nurse that I’ve ever come across is really in it for the patients. They are so knowledgeable, they’re so there.

And as far as the patients, have that communication with your nurses, talk to them. You may not see them on your next appointment, but they’ll give you whatever information that you need.

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Community Helped a Patient When Their MPN Treatment Was Delayed

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Brielle Benyon

Thomas Silver discusses how a community of support helped a patient when his bone marrow transplant was delayed.

Undergoing treatment for a myeloproliferative neoplasm (MPN) can be extremely lonely, so it is beneficial to have a support system throughout the process, explained Thomas Silver, board president of the Cancer Research and Treatment Fund in New York.

Silver, who was also recognized at CURE®’s 11th annual MPN Heroes® recognition event, told the story of his friend, Nick, an MPN survivor who was preparing to undergo a bone marrow transplant — which is currently the only curative therapy for MPNs — before he caught a common cold and had to have the procedure pushed back.

“Well, a month in his life is a long time,” Silver said.

However, Nick, Silver and a group of others are a part of a community that was able to offer support and stay in touch with Nick, who eventually went on to receive the transplant and is doing well, according to Silver.

Transcript

Well, it can be fairly lonely. It’s a really long, hard task. I remember talking to Nick when he was going through his through his trials and his journey. One of the things that happened was he was all ready to go with his transplant. And just a week or two beforehand, he developed a common cold and imagine being ready to go. And then you develop a cold. And they say, “Well, now because you have cold, you’ve got to wait another month.”

Well, a month in his life is a long time. So, the fact that we were around, we were available to talk to him, Nick and I are part of a large fraternity house and we have a number of brothers that we continue to stay in touch with. You have a great time with all the time. Just help him keep his spirits up when he was waiting that extra month to be able to actually begin the process of getting better.

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MPN Outcomes Have Improved in the Last 20 Years

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Brielle Benyon

Years ago, when Dr. Shamim Salman started treating patients with myeloproliferative neoplasms (MPNs), she, unfortunately saw many patients die from the disease because there was limited knowledge and treatment options.

However, outcomes are much better now with the advent of new therapies such as JAK inhibitors, Salman, hematologist-oncologist at Richmond University Medical Center in Staten Island, New York, said in an interview with CURE®.

“But now I’ve seen so many new things, so much research, so many new drugs and I’m so happy about it,” Salman, who was also honored at the 11th annual MPN Heroes® recognition event. “My patients are living longer. I feel so happy.”

Transcription

I have seen with my own eyes so many patients are dying with myeloproliferative neoplasms, especially I will mention myelofibrosis. I had so many patients (die because) at that time (when I started), there was no (knowledge of) JAK2, no JAK inhibitors, nothing. And patients would ask me, or their daughters or their sons (would ask), “Doctor, you will do something, right? You will make my mom better?” And I would say, “We will try.”

But now I’ve seen so many new things, so much research, so many new drugs and I’m so happy about it. My patients are living longer. I feel so happy. My patients 20 years ago, they died much sooner. They couldn’t see their granddaughter’s wedding or whatever their dreams were. Sometimes, I cried for them because I knew there’s nothing.

Not everybody was eligible for bone marrow transplant because some of them were elderly. Bone marrow transplant was there. I have sent my patient with myelofibrosis for bone marrow transplant. But unfortunately, if they were elderly, they died of the complications. So I tell my fellows, “You guys are so lucky now, so many drugs, so many research, so many things going on.”

And usually, my style is if I see a case, I tell them, go read about it today. And by the end of the day, again, we will talk and do look for clinical trials, look for the new research. I’m in Staten Island, but I’m connected with all the big institutions. And from the day one, we try to do the right thing for them.

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