MRD Levels Help Determine Appropriate B-Cell Precursor ALL Therapy

Among patients with B-cell precursor acute lymphoblastic leukemia (ALL), those with late bone marrow relapses and low minimal residual disease (MRD) have favorable outcomes with chemotherapy, whereas those with high MRD may benefit from more experimental therapies, according to a long-term follow-up analysis of the ALLR3 clinical trial (Lancet Haematol. 2019 Feb 27. Epub ahead of print).

Catriona Parker, PhD, Children’s Cancer Group, Division of Cancer Sciences, School of Medical Sciences, University of Manchester, United Kingdom, and colleagues examined the long-term follow-up outcomes of the ALLR3 trial, which investigated outcomes among patients aged 1 to 18 years with B-cell precursor ALL.

The open-label ALLR3 trial recruited 228 patients who had late bone marrow relapses from centers across Australia, the Netherlands, New Zealand, and the United Kingdom.

Between January 31, 2003 and December 31, 2007, patients were randomized to receive idarubicin or mitoxantrone during induction. Once induction ended, all patients were allocated to receive mitoxantrone.

After 3 blocks of therapy, patients with high MRD (≥10−4 cells) at the end of induction were allocated to undergo allogenic stem-cell transplantation (aSCT) and patients with low MRD (<10−4 cells) were allocated to receive chemotherapy.

Investigators measured MRD level by real-time quantitative PCR analysis of immunoglobulin and T-cell receptor gene rearrangements.

The primary end point of this follow-up long-term analysis was progression-free-survival (PFS) of patients with late bone marrow relapses stratified by MRD level.

Patients were treated between February 2, 2003, and October 28, 2013. After a median follow-up of 84 months, the PFS of all randomized patients was 60%.

A total of 220 patients achieved second complete remission, and MRD was evaluable in 192 (87%) patients. Of these evaluable patients, 110 were allocated to undergo aSCT, and 82 were allocated to receive chemotherapy.

Among patients allocated to undergo aSCT, 4 relapses and 3 deaths were reported before the procedure, and 11 did not undergo transplantation. Of the 92 patients who underwent aSCT, 58 (63%) remained in second complete remission, 13 (14%) died from complications, and 21 (23%) had relapsed disease.

Among patients allocated to chemotherapy, 1 early treatment-related death was reported, and 11 patients received aSCT instead. Of the 70 patients who continued to receive chemotherapy, 49 (70%) remained in second complete remission, 2 (3%) died from complications, and 19 (27%) had relapsed disease.

At 5 years, PFS was 56% in those with high MRD and 72% in those with low MRD (P = .0078).

“[Patients with B-cell precursor ALL] with late bone marrow relapses and low minimal residual disease at end of induction had favourable outcomes with chemotherapy without undergoing stem-cell transplantation,” concluded Dr Parker and colleagues.

 “Patients with high minimal residual disease benefited from stem-cell transplantation, and targeted therapies might offer further improvements in outcomes for these patients,” they added.—Janelle Bradley