Venetoclax for Leukemia, Biphenotypic, Acute

There is no difference between the two treatment groups in OS or DFS. A difference was found in DSS, with the conventional group having prolonged DSS and a better disease-free status at last visit as compared with the high-dose cyclophosphamide group. These data seem to justify further use of high-dose cyclophosphamide as initial therapy in patients with acute leukemia, biphenotypic, expressing B-cell markers.

The disease causes by one of two mechanisms: chromosomal abnormalities cause specific gene mutations, which in turn affect the development of leukemia, or exposure to certain [environmental factors can affect development of leukemia.] This latter effect causes the development of all variants of leukemia, biphenotypic and acute.

The signs of leukemia, biphenotypic, acute may include the following: bleeding time longer than 90 seconds, bleeding time longer than 60 seconds and hematocrit less than 35%. In the case of chronic disease, the signs of leukemia, biphenotypic, acutely are fatigue, weight loss, bone and joint pains, fever, anemia, and jaundice or yellowing of the skin or whites of the eyes.

Treatment of leukemia often depends on several factors, including specific presentation of the disease, whether or not it is behaving like a leukemoid blast crisis, whether or not the leukemia has entered complete remission, and whether remission is sustained. One-third of patients will require allogeneic stem-cell transplant, and/or other high-intensity therapy to remit leukemia. Patients presenting with a leukemoid blast crisis but sustained complete remission generally have a longer disease-free survival, but their overall survivals are still poor. Patients with B-lymphoblastic leukaemia have some of the best cure rates and longest disease-free survivals after achieving complete remission, but disease-specific relapses are still a problem for many.

Leukemia, biphenotypic, acute, is the most common type of leukemia and a disease from which most people with circulating leukemias die within 5 years after diagnosis. It is a heterogeneous collection of blood diseases characterized by the presence of two or more leukemic cell populations, leukemic blasts or abnormal blood cells and disease-related cytogenetic abnormalities.

If a diagnosis of B-PPA is made, then it is not uncommon for patients diagnosed with B-PPA to have an acute leukemia. B-PPA is a rare cause of acute leukemia, and an increase in the incidence and rate of leukemia related to B-PPA in children is expected if there is a genetic predisposition for this condition. The use of the B-PPA label on Medicare claims is not a reliable way of estimating the number of new cases of leukemia that occur in the United States each year.

Although the primary endpoint of the VENTURE 1 trial (first progression) was reached sooner by the treatment group, and OS and progression-free survival were significantly improved at 9 and 11.3 months, the data suggest that the benefit of venetoclax (vs. a placebo) in the secondary endpoint (safety) was not statistically significant. More data are needed to determine the impact of this secondary outcome. There are additional questions to ask about optimal treatment duration, the optimal selection and dose of venetoclax in clinical practice, and the effect of combination therapy (vs. monotherapy) on OS and progression-free survival. Results from a recent paper were presented at the ASCO 2016 Annual Meeting.

There are many cases where an elderly sibling with lymphoma or leukemia has developed a second malignancy as well as a young offspring with a hematologic complication of the acute disease. The possibility of a hematologic malignancy must be considered in these cases.

More than 25% of patients treated were affected by AE. The most common AE were diarrhea and thrombocytopenia. Hematologic side effects and infections (especially infections in the respiratory tract) were the most frequent. AE might be caused by venetoclax itself or by the combination used (with cytarabine).

Venetoclax is an investigational drug used to treat chronic lymphocytic leukemia (CLL), myelodysplastic syndrome (MDS), and multiple myeloma (MM) in adults (aged > 18 years) and of ALL in children (aged < 18 years) on a continuous basis in clinical trials. The FDA issued a statement on venetoclax in October 2018 stating that more information about its safety and effectiveness is required.

For patients with treatment indication for FLT3 inhibitors, venetoclax achieves significant and clinically significant responses when used in the recommended dose and schedule. This data further support venetoclax as a potential treatment option for a broader population.