9 mei 2021: Bron: Journal of Clinical Oncology

Uit een fase III, multicenter, gerandomiseerde studie blijkt de werkzaamheid van vincristine / dexamethasonpulsen met verminderde frequentie en alternatieve dosering van methotrexaat voor patiënten met All - B-acute lymfoblastische leukemie met standaardrisico tijdens de onderhoudsfase geen effect te hebben op de ziektevrije tijd en op de mediane overall overleving. Wel blijken de bijwerkingen veel minder te zijn en kwaliteit van leven daardoor beter.

Het gebruik van vincristine / dexamethason elke 12 weken versus elke 4 weken had geen significante invloed op de ziektevrije overleving (DFS) of algehele overleving (OS) na 5 jaar. Evenzo verbeterde het verhogen van de dosis oraal methotrexaat van 20 mg naar 40 mg de ziektevrije overleving of de OS na 5 jaar niet significant.

De onderzoekers stellen dat een verlaagde frequentie van vincristine en dexamethason kan in behandelingsprotocollen worden opgenomen om de belasting van de therapie bij deze patiëntenpopulatie te verminderen.

Het volledige studierapport is tegen betaling in te zien. Hier het abstract van de studie:

Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932

Anne L. Angiolillo, MD1,2 ; Reuven J. Schore, MD1,2; John A. Kairalla, PhD3; Meenakshi Devidas, PhD4; Karen R. Rabin, MD, PhD5; Patrick Zweidler-McKay, MD, PhD6; ...Show More

*A.L.A. and R.J.S. contributed equally as first authors. E.A.R., M.L.L., and S.P.H. contributed equally as senior authors.

https://doi.org/10.1200/JCO.20.00494

Abstract

Purpose:

AALL0932 evaluated two randomized maintenance interventions to optimize disease-free survival (DFS) while reducing the burden of therapy in children with newly diagnosed NCI standard-risk (SR) B-acute lymphoblastic leukemia (B-ALL).

Methods:

AALL0932 enrolled 9,229 patients with B-ALL; 2,364 average-risk (AR) patients were randomly assigned (2 × 2 factorial design) at the start of maintenance therapy to vincristine/dexamethasone pulses every 4 (VCR/DEX4) or every 12 (VCR/DEX12) weeks, and a starting dose of weekly oral methotrexate of 20 mg/m2 (MTX20) or 40 mg/m2 (MTX40).

Results:

Five-year event-free survival and overall survival (OS) from enrollment (with 95% CIs), for all eligible and evaluable SR B-ALL patients (n = 9,226), were 92.0% (91.1% and 92.8%) and 96.8% (96.2% and 97.3%), respectively. The 5-year DFS and OS from the start of maintenance for randomly assigned AR patients were 94.6% (93.3% and 95.9%) and 98.5% (97.7% and 99.2%), respectively. The 5-year DFS and OS for patients randomly assigned to receive VCR/DEX4 (n = 1,186) versus VCR/DEX12 (n = 1,178) were 94.1% (92.2% and 96.0%) and 98.3% (97.2% and 99.4%) v 95.1% (93.3% and 96.9%) and 98.6% (97.7% and 99.6%), respectively (P = .86 and .69). The 5-year DFS and OS for AR patients randomly assigned to receive MTX20 versus MTX40 were 95.1% (93.3% and 96.8%) and 98.8% (97.9% and 99.7%) v 94.2% (92.2% and 96.1%) and 98.1% (97.0% and 99.2%), respectively (P = .92 and .89).

Conclusions:

The 0NCI-SR AR B-ALL who received VCR/DEX12 had outstanding outcomes despite receiving one third of the vincristine/dexamethasone pulses previously used as standard of care on Children's Oncology Group (COG) trials. The higher starting dose of MTX of 40 mg/m2/week did not improve outcomes when compared with 20 mg/m2/week. The decreased frequency of vincristine/dexamethasone pulses has been incorporated into frontline COG B-ALL trials to decrease the burden of therapy for patients and their families.

CONTEXT

Key Objective
Can maintenance therapy in patients with newly diagnosed National Cancer Institute (NCI) standard-risk (SR) B-acute lymphoblastic leukemia (B-ALL) be optimized to improve disease-free survival (DFS) and reduce the burden of therapy?
Knowledge Generated
In the context of modern Children's Oncology Group (COG) therapy, vincristine/dexamethasone pulses administered every 12 weeks demonstrated excellent outcomes. Increasing the starting dose of oral methotrexate from 20 to 40 mg/m2/wk in maintenance did not improve DFS.
Relevance
Excellent treatment outcomes in NCI SR B-ALL have been achieved with a decreased frequency of vincristine/dexamethasone pulses while decreasing the burden of therapy. COG has adopted this change in new B-ALL trials.