This article is more than 5 years old. Information may no longer be current.
Studies highlight exciting trends in prognostic markers, combinations for myelofibrosis
Click Here to Manage Email Alerts
At the December ASH Annual Meeting and Exposition, there were many exciting abstracts in myeloproliferative neoplasms, particularly in myelofibrosis. We are seeing advances in science, as well as in prognosis and clinical care, that are energizing the field.
Regarding advances in science, notably, Elf and colleagues presented a late-breaking abstract that builds on the story of calreticulin (CALR) mutations, which are recurrent in patients with myelofibrosis. We are now beginning to understand the biology of how this mutation drives the disease, and their work indicates that mutant CALR activates the canonical JAK-STAT pathway through interaction with the thrombopoietin receptor, MPL.
Other abstracts that were presented looked at prognostic aspects of myelofibrosis. For instance, there was a “well, duh” moment when results of an abstract — presented by Guglielmelli and colleagues — showed the bone marrow fibrosis grade correlated with clinical outcomes. The grade also correlated with clinical parameters — such as International Prognostic Scoring System category, High-Molecular Risk (HMR) status, number of HMR-mutated genes and driver mutations — that we know predict outcomes, and even with genetic mutations that we see in the cells of patients with myelofibrosis. These data linked older prognostic indicators with more recent prognostic indicators, putting the whole picture together.
Key clinical trial results were presented, as well, including some very large studies. For example, Harrison and colleagues shared the final analysis of the COMFORT-II trial, a pivotal study that led to regulatory approval for ruxolitinib (Jakafi, Incyte). The long and short of these results were that patients who are on ruxolitinib, and doing very well, will continue to do very well for many years. Patients who are on ruxolitinib and have a 35% or greater reduction in spleen volume have a 48% chance of continued benefit at 5 years. These are really important long-term results.
Vannucchi and colleagues presented data from a subgroup analysis of the PERSIST-1 trial, which demonstrated benefit — regarding spleen volume reduction and improvement in Total Symptom Score — with pacritinib (CTI Biopharma) vs. best available therapy for all patient subgroups. However, since these data were presented, the FDA placed pacritinib on full clinical hold to evaluate reports of patient deaths related to intracranial hemorrhage, cardiac failure and cardiac arrest in this and the phase 3 PERSIST-2 trial.
There also were many abstracts presented on interferon, the story of which continues to unravel. There appears to be high toxicity, but there is efficacy, as well, and we are still learning how to use this medication, with pivotal trials ongoing. Early results from a trial with the antifibrotic agent PRM-151 (Promedior) were presented by Verstovsek and colleagues, a top-line item of discussion among those in the myeloproliferative neoplasm community.
ASH also featured many combination trials — the next exciting thing in myelofibrosis. Early results were presented on combining JAK inhibition with HDAC inhibitors and JAK inhibition plus smoothened inhibitors, among others.
We are still learning how best to combine these agents. These trials have demonstrated more toxicity than we would hope, but by further use and exploration, we hope to reign in the toxicity and increase efficacy for our patients.
References:
The following were presented at the ASH Annual Meeting and Exposition; Dec. 5-8, 2015; Orlando, Fla.:
Elf S, et al. Abstract LBA-4.
Guglielmelli P, et al. Abstract 351.
Harrison CN, et al. Abstract 59.
Vannucchi AM, et al. Abstract 58.
Verstovsek S, et al. Abstract 56.
For more information:
Aaron Gerds, MD, is assistant professor in medicine (hematology and medical oncology) at Cleveland Clinic Taussig Cancer Institute. He can be reached at gerdsa@ccf.org.
Disclosure: Gerds reports no relevant financial disclosures.
Editor’s note: For more details on the FDA’s clinical hold on pacritinib, click here.