Expert review of hematology
-
Myelofibrosis (MF) is characterized by bone marrow fibrosis with subsequent extramedullary hematopoiesis and abnormal cytokine expression leading to splenomegaly, constitutional symptoms and cytopenias. The discovery of the JAK2 V617F mutation in the majority of MF patients has been followed by significant progress in drug development for MF. Areas covered: In this article, we review advances in the understanding of the underlying disease biology, prognostic assessment and therapeutic modalities for MF. ⋯ Expert commentary: Despite significant reduction of splenomegaly and improvement of symptom burden and a signal for survival improvement, ruxolitinib does not lead to major reductions in JAK2 V617F allele burden and bone marrow fibrosis. No ruxolitinib-based combination approach has so far demonstrated superiority over ruxolitinib monotherapy. The novel JAK2 inhibitors pacritinib and momelotinib, other JAK inhibitors, telomerase inhibitors, anti-fibrosis agents and hsp90 inhibitors are in different stages of development.
-
The therapy for chronic lymphocytic leukemia (CLL) is undergoing a major transformation. However, the seminal progresses realized to date with the use of novel agents, leave many practical questions unanswered. Areas covered: This review focuses on the recent data of the literature of small-kinase inhibitor (KI) molecules and how results of KI clinical trials may translate into current clinical practice. ⋯ Expert commentary: Nowadays the challenge is to apply the principles of chemotherapy to combine different targeted agents with nonoverlapping toxicities. This approach is not likely to immediately change the standard of care, however, it raises relevant questions concerning the optimal strategy for incorporating novel agents in the treatment of CLL. Given the increasing number of patients who have access to treatment with small-KI molecules, generally administered over an extended duration, more sustainable pricing for such therapies is needed.