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Physicians’ Education Resource®, LLC, is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

These activites are not approved for AMA PRA Category 1 Credit™.

Acknowledgment of Commercial Support

This activity is supported by educational grants from Gilead Sciences, Inc. and Incyte.

Cancer Summaries and Commentaries™: Update From San Diego: Advances in Myeloproliferative Neoplasms - PER Pulse™ Recap

PER Pulse Recap

PER Pulse™ Recap



1 of 3
PER Pulse Recap

Cancer Summaries and Commentaries™: Update From San Diego: Advances in Myeloproliferative Neoplasms is an online CME publication designed to update physicians on key clinical data on myeloproliferative neoplasms presented at the 2016 American Society of Hematology (ASH) Annual Meeting. The activity features audio commentary from Drs. Ruben Mesa and Srdan Verstovsek on how new data fit into the current field and, when appropriate, how clinicians can integrate these findings into practice to improve patient care.

This first of 3 PER Pulse™ Recaps summarizing the program focuses on discussion of 6-year follow-up data from phase I/II studies of the JAK1/2 inhibitor momelotinib for myelofibrosis (MF).

A phase I/II study (N = 166) of momelotinib demonstrated that this agent is active when used as therapy for patients with high- or intermediate-risk MF. The treatment was well tolerated and reduced MF-related splenomegaly, transfusion requirements, and symptom burden. Efficacy and safety data, based on sponsor-independent analyses of long-term data from 100 patients in the phase I/II study, were presented at the 2016 American Society of Clinical Oncology Annual Meeting. Briefly, these data demonstrated that momelotinib provides a benefit in terms of anemia, splenomegaly, and constitutional symptoms for a subset of patients. Notably, nearly half of patients experienced drug-related peripheral neuropathy that was often reversible. During their interviews about this abstract, Drs. Mesa and Verstovsek discuss:

  • The prospect of a therapy that improves splenomegaly, quality of life, and anemia is welcome.
  • Previous publications from phase I and II studies of this agent have reported conflicting outcomes with respect to an anemia response.
  • Approximately one-third of patients on momelotinib experience thrombocytopenia. The dichotomous effect that momelotinib has on platelets versus red blood cells is interesting, but the mechanism that accounts for this is not fully understood.
  • As a sponsor-independent effort, these analyses have not been fully vetted via the clinical trial process. Long-term data from large reference centers that have multiple studies are prone to multiple confounders (eg, competing studies).
  • Results of these analyses confirm previous reports from the same group, which led to the initiation of a phase III study with momelotinib. Top-line results from these trials, announced by the sponsor in November 2016, were mixed. Overall, additional investigations with this agent are needed to define its optimal use.
  • A phase II study of momelotinib is currently recruiting patients with MF who are transfusion-dependent (NCT02515630).


2 of 3
PER Pulse™ Recap

Cancer Summaries and Commentaries™: Update From San Diego: Advances in Myeloproliferative Neoplasms is an online CME publication designed to update physicians on key clinical data on myeloproliferative neoplasms presented at the 2016 American Society of Hematology (ASH) Annual Meeting. The activity features audio commentary from Drs. Ruben Mesa and Srdan Verstovsek on how new data fit into the current field and, when appropriate, how clinicians can integrate these findings into practice to improve patient care.

This second of 3 PER Pulse™ Recaps summarizing the program focuses on discussion of pooled 5-year overall survival (OS) data from the COMFORT-I and COMFORT-II studies of ruxolitinib, a selective inhibitor of JAK1 and JAK2.

Ruxolitinib is approved for use in the treatment of intermediate- or high-risk myelofibrosis (MF) and in polycythemia vera (PV) that is refractory to hydroxyurea (HU). Its efficacy in improving OS, splenomegaly, disease-related symptoms, and quality of life was demonstrated in the phase III COMFORT-I and COMFORT-II trials, which compared ruxolitinib with placebo and best available therapy (BAT), respectively. Long-term follow-up of participants in these trials is ongoing. Overall survival data from an exploratory pooled analysis of 5-year follow-up data from the COMFORT-I and COMFORT-II studies were presented at the 2016 American Society of Clinical Oncology Annual Meeting. Briefly, these data demonstrate that long-term treatment with ruxolitinib prolonged survival compared with BAT or placebo. Notably, differences in immediate versus delayed treatment effects with ruxolitinib were observed due to crossover. During their interviews about this abstract, Drs. Mesa and Verstovsek discuss:

  • Among the intent-to-treat population, ruxolitinib extended life by approximately 1.5 years versus BAT or placebo. This survival benefit accounts for patient crossover from the control arms to the ruxolitinib arms.
  • Among patients who received ruxolitinib from randomization, the survival benefit with ruxolitinib was approximately 3 years compared with patients who never received ruxolitinib.
  • Collectively, these data suggest that eligible patients will benefit from receiving ruxolitinib early in the course of their disease.
  • Concerns have been raised about whether transfusion dependence among a subset of patients negates the benefits of ruxolitinib. However, the long-term OS data suggest that this is not a priority concern.

3 of 3
PER Pulse™ Recap

Cancer Summaries and Commentaries™: Update From San Diego: Advances in Myeloproliferative Neoplasms is an online CME publication designed to update physicians on key clinical data on myeloproliferative neoplasms presented at the 2016 American Society of Hematology (ASH) Annual Meeting. The activity features audio commentary from Drs. Ruben Mesa and Srdan Verstovsek on how new data fit into the current field and, when appropriate, how clinicians can integrate these findings into practice to improve patient care.

This third of 3 PER Pulse™ Recaps summarizing the program focuses on discussion of interim data from the Myeloproliferative Disorders Research Consortium (MPD-RC) 112 global phase III trial of frontline pegylated interferon alpha-2a (peginterferon) versus hydroxyurea (HU).

Frontline HU is the standard of care for high-risk polycythemia vera (PV) and essential thrombocythemia (ET), and reduces thrombotic risk. However, HU does not eradicate malignant clones, and some controversy exists about association with long-term leukemogenic risk. Interferon is a nonleukemogenic therapy that may preferentially target the malignant clone in PV. The severe toxicities associated with conventional interferon limit its use. In phase II studies, peginterferon was clinically active and better tolerated (dropout rate due to toxicity <10%). Interim results from the MPD-RC’s phase III trial comparing frontline peginterferon with HU were presented at the 2016 American Society of Clinical Oncology Annual Meeting. Briefly, these interim data demonstrated no meaningful difference in the primary endpoint between the HU and peginterferon arms of this study. During their interviews about this abstract, Drs. Mesa and Verstovsek discuss:

  • Data from modern studies that have mitigated concerns that HU is a primary culprit in leukemic transformation among this patient population. Nonetheless, physicians should be cautious when considering HU for younger patients who may require decades of therapy.
  • The toxicities associated with peginterferon and HU differ in character, as well as in time of onset and resolution. Both agents increased patient symptom burden to some extent.
  • These interim results were not unexpected, and it would not be surprising for longer-term follow-up to demonstrate superior efficacy outcomes with peginterferon versus HU, particularly for bone marrow and molecular responses.







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