Blood cancers

PET status highly predictive of ASCT outcome in follicular lymphoma

PET-CT scan status can predict outcomes of autologous stem cell transplantation (ASCT) in patients with relapsed/refractory follicular lymphoma (R/R FL), which could help stratify those most likely to benefit from the treatment, a study has shown.

The findings demonstrate for the first time that patients with R/R FL who achieve a PET-negative remission (complete metabolic remission; CMR) before consolidation autoSCT “have significantly improved PFS compared to those patients who fail to achieve CMR”, according to UK researchers from the Oxford University Hospitals NHS Foundation Trust.

Their retrospective study, published in Haematologica, involved 172 R/R FL patients within the multicentre BSBMTCT registry study, who had received a median number of three prior lines of therapy pre-autoSCT.

It found that those determined to be in CMR via a PET scan prior to transplant had a 50% chance of remaining alive and progression free at 3 years, compared to 22% of those who failed to achieve a CMR.

Also, in multivariate analysis, PET status was independently linked with PFS (non-CMR HR 2.02), overall survival (3.08) and risk for relapse (1.64) post ASCT, the researchers led by Dr Toby Eyre, a Haematology Consultant at Churchill Hospital, said.

As ASCT is linked with a risk of non-relapse mortality, significant morbidity, prolonged in-patient admission and secondary haematological malignancy and also incurs significant cost, “it is important that the ability to predict patients who may be expected to have long remissions with this intensive treatment are improved,” they said.

At the same time, it is crucial that tools able to predict which patients are likely to have short-lived benefit from ASCT are developed, “so that alternative treatment modalities can be assessed in this group and avoid exposing patients to this potentially toxic treatment”.

Data from the trial also support use of ASCT in consolidating remissions in patients with R/R FL, showing median PFS of 28 months and a 3-year PFS rate of 40% for the whole cohort. “If this intervention can be further refined so that it is directed towards those most likely to benefit, the outcomes for patients undergoing this procedure may be further improved,” the researchers noted.

In a linked editorial, Dr Clémentine Sarkozy and colleagues from the Gustave Roussy Hospital, Paris, said the data “indicate that ASCT is unlikely to provide a benefit for non-CMR patients although it is unknown if another strategy would improve their outcome.”

“The main pitfall of the study is the heterogeneity of patients and prior therapies, inherent to its retrospective design. But these results further add to others supporting the use of PET-CT as a valuable predictive tool in patients with FL”.

They also urged caution over interpreting the findings in the context of FL management.

For one, the study “does not establish if ASCT constitutes an optimal therapeutic strategy for patients with chemosensitive relapsed FL, including those with an early disease progression”.

Also, “lenalidomide with anti-CD20 antibody combinations provide already a widely used alternative to cytotoxic regimens,” while CAR T-cells are also emerging “as very effective tools even for those with refractory disease” and “other forms of efficient immunotherapies such as bispecific antibodies will likely be available soon”.

“As always with follicular lymphoma, tradeoff between toxicity and efficacy, as well as costs and patients’ preference, will play a role regarding the optimal sequencing of these therapies. Thus, given the uncertainty for current and future management, the reported findings by Eyre et al. need to be cautiously interpreted,” they wrote.

Nevertheless, the paper’s authors stressed that “although there are many new treatment options in development for R/R FL, there are few that have yet demonstrated remissions as durable as those achieved by autoSCT in the historical literature and in patients in this study who achieved CMR to autoSCT”.

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