What is Hyper-CVAD (Hyperfractionated Cyclophosphamide, Vincristine, Doxorubicin, and Dexamethasone)?

From the Guidelines

The Hyper-CVAD regimen is a suitable treatment option for patients with acute lymphoblastic leukemia (ALL), particularly those with aggressive disease, and consists of alternating cycles of two different combination chemotherapy regimens, with Course A including cyclophosphamide, vincristine, doxorubicin, and dexamethasone, and Course B including methotrexate and cytarabine, as supported by the most recent study from 2019 1. The Hyper-CVAD regimen is used primarily for treating aggressive lymphomas and leukemias, particularly ALL and mantle cell lymphoma.

• The regimen involves 4-8 cycles total, with courses A and B alternating every 21 days, though this may vary based on patient response and tolerance.
• This intensive chemotherapy approach is designed to rapidly reduce cancer cell populations through multiple mechanisms of action.
• Patients receiving Hyper-CVAD require close monitoring for side effects including myelosuppression (low blood counts), infections, mucositis, and neuropathy, as noted in the study from 2012 1.
• Supportive care with growth factors, antimicrobial prophylaxis, and antiemetics is typically provided throughout treatment, as recommended in the guidelines from 2019 1.
• The regimen's intensity makes it most appropriate for younger patients or those with good performance status, though modified versions exist for older or less fit patients, as discussed in the study from 2012 1. The use of Hyper-CVAD has been associated with improved outcomes in patients with ALL, particularly those with CD20-positive disease, when combined with rituximab, as shown in the study from 2019 1.
• However, older patients (aged ≥60 years) with CD20-positive disease demonstrated higher rates of MRD negativity with the inclusion of rituximab, but this did not translate into a survival benefit, largely due to increased mortality in CR.
• The high rate of death in CR for older patients may relate to anthracycline intensification as opposed to inclusion of rituximab, as noted in the study from 2019 1.

From the Research

Tabel Hyper-CVAD

• The Hyper-CVAD regimen is a dose-intensive chemotherapy treatment used for adult acute lymphocytic leukemia (ALL) and lymphoblastic lymphoma 2, 3, 4, 5, 6.
• The regimen consists of fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone, and is often alternated with high-dose methotrexate and cytarabine therapy 2, 5.
• Studies have shown that the Hyper-CVAD regimen is effective in achieving complete remission in adult ALL patients, with complete remission rates ranging from 74% to 91% 2, 3, 5, 6.
• The regimen has also been shown to have a low incidence of CNS relapse, with rates ranging from 4% to 9% 2, 5.
• Comparison of the Hyper-CVAD regimen with other chemotherapy regimens, such as the BFM-like regimen, has shown similar overall survival and disease-free survival rates 6.
• The Hyper-CVAD regimen is generally well-tolerated, although it can be associated with significant toxicity, particularly in older patients or those with comorbidities 3, 5, 6.

Efficacy of Hyper-CVAD

• A study published in 2004 found that 91% of patients with lymphoblastic lymphoma achieved complete remission with the Hyper-CVAD regimen, with a 3-year progression-free survival rate of 66% and a 3-year overall survival rate of 70% 2.
• A study published in 2018 found that 81.7% of patients with ALL achieved complete remission with a modified Hyper-CVAD regimen, with a 5-year overall survival rate of 51.8% 3.
• A study published in 2000 found that 91% of patients with ALL achieved complete remission with the Hyper-CVAD regimen, with a 5-year survival rate of 39% and a 5-year complete remission rate of 38% 5.
• A study published in 2017 found that the Hyper-CVAD regimen was associated with similar overall survival and disease-free survival rates compared to the BFM-like regimen, with a 3-year overall survival rate of 71.9% and a 3-year disease-free survival rate of 54.7% 6.

Toxicity and Tolerability

• The Hyper-CVAD regimen can be associated with significant toxicity, particularly in older patients or those with comorbidities 3, 5, 6.
• Common toxicities include myelosuppression, infection, and mucositis 3, 5, 6.
• Studies have shown that the regimen is generally well-tolerated, although dose reductions and delays may be necessary in some patients 3, 5, 6.