Ruxolitinib in patients with polycythemia vera resistant and/or intolerant to hydroxyurea: European observational study.

BACKGROUND: Hydroxyurea (HU) is a commonly used first-line treatment in patients with polycythemia vera (PV). However, approximately 15%-24% of PV patients report intolerance and resistance to HU. METHODS: This phase IV, European, real-world, observational study assessed the efficacy and safety of ruxolitinib in PV patients who were resistant and/or intolerant to HU, with a 24-month follow-up. The primary objective was to describe the profile and disease burden of PV patients. RESULTS: In the 350 enrolled patients, 70% were >60 years old. Most patients (59.4%) had received ≥1 phlebotomy in the 12 months prior to the first dose of ruxolitinib. Overall, 68.2% of patients achieved hematocrit control with 92.3% patients having hematocrit <45% and 35.4% achieved hematologic remission at month 24. 85.1% of patients had no phlebotomies during the study. Treatment-related adverse events were reported in 54.3% of patients and the most common event was anemia (22.6%). Of the 10 reported deaths, two were suspected to be study drug-related. CONCLUSION: This study demonstrates that ruxolitinib treatment in PV maintains durable hematocrit control with a decrease in the number of phlebotomies in the majority of patients and was generally well tolerated.

A Phase I/II Open-Label Study of Molibresib for the Treatment of Relapsed/Refractory Hematologic Malignancies.

PURPOSE: Molibresib is a selective, small molecule inhibitor of the bromodomain and extra-terminal (BET) protein family. This was an open-label, two-part, Phase I/II study investigating molibresib monotherapy for the treatment of hematological malignancies (NCT01943851). PATIENTS AND METHODS: Part 1 (dose escalation) determined the recommended Phase 2 dose (RP2D) of molibresib in patients with acute myeloid leukemia (AML), Non-Hodgkin lymphoma (NHL), or multiple myeloma. Part 2 (dose expansion) investigated the safety and efficacy of molibresib at the RP2D in patients with relapsed/refractory myelodysplastic syndrome (MDS; as well as AML evolved from antecedent MDS) or cutaneous T-cell lymphoma (CTCL). The primary endpoint in Part 1 was safety and the primary endpoint in Part 2 was objective response rate (ORR). RESULTS: There were 111 patients enrolled (87 in Part 1, 24 in Part 2). Molibresib RP2Ds of 75 mg daily (for MDS) and 60 mg daily (for CTCL) were selected. Most common Grade 3+ adverse events included thrombocytopenia (37%), anemia (15%), and febrile neutropenia (15%). Six patients achieved complete responses [3 in Part 1 (2 AML, 1 NHL), 3 in Part 2 (MDS)], and 7 patients achieved partial responses [6 in Part 1 (4 AML, 2 NHL), 1 in Part 2 (MDS)]. The ORRs for Part 1, Part 2, and the total study population were 10% [95% confidence interval (CI), 4.8-18.7], 25% (95% CI, 7.3-52.4), and 13% (95% CI, 6.9-20.6), respectively. CONCLUSIONS: While antitumor activity was observed with molibresib, use was limited by gastrointestinal and thrombocytopenia toxicities. Investigations of molibresib as part of combination regimens may be warranted.

Multivariable time-dependent analysis of the impact of azacitidine in patients with lower-risk myelodysplastic syndrome and unfavorable specific lower-risk score.

Scoring systems for lower-risk myelodysplastic syndrome (LR-MDS) recognize patients with a poorer than expected outcome. This study retrospectively analyzes the role of azacitidine in LR-MDS with adverse risk score and compared to an historical cohort treated with best supportive care or erythropoiesis-stimulating agents. Overall response to AZA was 40%. One and 2-year probabilities of survival were 62% and 45% for AZA vs. 25% and 11% (P=10(-4)). In a multivariable time-dependent analysis, response to AZA (CR/PR/HI) was associated with an improved survival (HR=0.234, 95% CI, 0.063-0.0863; P=0.029). Thrombocytopenia (<50 × 10(9)L(-1)) is confirmed as an adverse parameter in LR-MDS (HR=1.649, 95% CI, 1.012-2.687; P=0.045).

Azacytidine for the treatment of myelodysplastic syndromes in the elderly.

The management of myelodysplastic syndromes (MDS) in elderly patients is a significant clinical problem. The therapeutic options range from observation alone for patients with low-risk disease, lenalidomide for patients with 5q-syndrome, to 5-azacytidine (5-AZA) for patients with higher risk of disease. In this paper, we summarize the clinical course of three patients with high-risk MDS treated with 5-AZA as well as the management and supportive care measures for adverse events. As expected, based on available clinical trials data, the agent resulted in clinical and hematological improvement in these patients with acceptable side effects. 5-AZA is an attractive option for elderly patients with high-risk MDS.