Combining positron emission tomography (PET) with tumour gene expression profiling straight after therapy might be able to determine which sufferers with early stage classical Hodgkin lymphoma (cHL) are more likely to expertise illness development or one other occasion throughout follow-up, suggests an evaluation of UK trial information.
The analysis was offered on the digital 62nd American Society of Hematology (ASH) Annual Assembly and Exposition on December 7.
The examine was a sub-analysis of the UK Nationwide Most cancers Analysis Institute’s RAPID scientific trial, which examined whether or not sufferers with a adverse PET scan after three cycles of doxorubicin hydrochloride, bleomycin sulfate, vinblastine, and dacarbazine (ABVD) chemotherapy wanted consolidation radiotherapy to delay or forestall illness development.
For the present evaluation, tumour samples from greater than 220 sufferers from RAPID underwent gene expression profiling.
This recognized three genes considerably related to the danger of a cHL occasion throughout follow-up: the 2 immune cell-related genes IL15RA and CD22, and the apoptosis-related gene BID.
A mannequin combining the three genes with interim PET scores was considerably predictive of sufferers at excessive versus low threat of a cHL-related occasion throughout follow-up, with a excessive rating related to a greater than eightfold elevated threat of an occasion.
Presenting the findings, Dr Kim Linton, College of Manchester and The Christie NHS Basis Belief, Manchester, stated the mannequin confirmed “promising utility for enhanced prediction of cHL event-free survival” in early stage illness, independently of broadly used pre-treatment scientific threat scores.
She believes the findings “warrant additional analysis in an unbiased cohort”, with the purpose of “enhancing the precision of individualised therapy to enhance illness management and minimise late toxicity”.
Dr Linton added the outcomes additionally validate earlier stories indicating that overexpression of the B-cell marker CD22 has a protecting operate in cHL, thus “conferring a extra beneficial end result”.
Dr Catherine Diefenbach, director of the scientific lymphoma program at New York College Langone’s Perlmutter Most cancers Heart, who was not concerned within the examine, spoke to Medscape Information UK.
She stated the examine is “attention-grabbing, and I believe threat stratification in Hodgkin’s lymphoma is de facto necessary, particularly as a result of…we actually need to spare the sufferers who’re going to do effectively as a lot therapy as attainable so we spare them long-term uncomfortable side effects”.
She continued that clinicians additionally “need to not minimise however deal with to treatment the sufferers who’re on the highest threat of relapse, in order that’s actually our aim with Hodgkin lymphoma sufferers”.
Dr Diefenbach stated that the present examine however has a few caveats, the “largest one” being that “this can be a non-validated examine”, in that the evaluation was run on the total dataset with no unbiased validation in a separate cohort of sufferers.
Furthermore, “there are so few occasions” through the follow-up interval, “which is an efficient factor for sufferers however it’s exhausting to know the importance” of the mannequin “with this small variety of occasions”.
The outcomes subsequently require affirmation in additional research earlier than the mannequin may be stated to be “prepared for prime time”.
When it comes to its potential position in relation to different threat stratification scores, Dr Diefenbach, who designed the IPS-3 score for advanced Hodgkin lymphoma, stated the “entire aim with these scientific threat scores is to have the ability to mix them with a biologic threat rating so that you could get enhanced threat profiling, and actually personalised drugs”.
She added that they’re “not competing with one another”, and the present mannequin is distinguished from most different threat scores because of being designed for post-treatment evaluation, which may “let you know for instance, if it was validated, if you should increase remedy or get away with doing much less for a specific affected person”.
Dr Linton started her presentation by noting that, whereas mixed modality therapy is the usual of look after early stage cHL, long-term survival is undermined by late toxicities, leading to sufferers, over time, being twice as probably in the end to die from therapy toxicity as from the illness itself.
Though a adverse interim PET scan after as much as three cycles of ABVD is ready to predict a low relapse charge in sufferers with non-bulky stage 1a/2a cHL, a number of research have proven that it isn’t, by itself, capable of choose sufferers appropriate for omission of radiotherapy.
To find out whether or not gene expression profiles in diagnostic tumour tissue may enhance affected person choice, the researchers carried out BioPET, a sub-analysis of the RAPID trial.
For RAPID, 571 cHL sufferers with stage 1a/2a illness and no mediastinal bulk have been handled with three cycles of ABVD.
The 426 sufferers who subsequently had a whole metabolic response rating of 1 or 2 have been then randomised to 30 Gy of involved-field radiation therapy (IFRT) or no additional remedy. The 145 sufferers who had a optimistic PET, outlined as a rating of three–5, got a fourth cycle of ABVD after which IFRT.
Sufferers have been included within the BioPET evaluation if they’d undergone a pre-treatment European Organisation for Analysis and Therapy of Most cancers (EORTC) and German Hodgkin Research Group (GHSG) threat evaluation and had 3 years of event-free survival information following therapy.
To conduct the gene profiling, they chose 57 candidate gene biomarkers from dysregulated pathways in cHL, and used a normal assay (Quantigene Plex 2.0, ThermoFisher Scientific) to evaluate every affected person’s gene expression profile.
They have been capable of study 227 affected person samples from the RAPID trial, alongside 15 RNA reference controls and 12 formalin-fixed, paraffin-embedded management tissue samples.
The median age of the sufferers was 36 years, 48.0% have been feminine and 71.4% had stage 2A illness. The pretreatment threat scores have been beneficial in roughly 66% of sufferers, and all three therapy arms have been effectively represented.
After a median follow-up of 55 months, there have been 21 cHL occasions.
After adjusting for therapy group, PRF1 and BCL2L1 genes have been considerably related to an interim PET rating of three–5 on multivariate evaluation, at odds ratios of 1.49 and 0.65, respectively (p=0.03 for each).
Three genes have been additionally considerably related to a cHL occasion on multivariate evaluation: IL15RA, at a hazard ratio of 0.33 (p=0.02); CD22, at a hazard ratio of 0.54 (p<0.001); and BID, at a hazard ratio of three.66 (p<0.001).
Combining CD22, BID and IL15RA expression with interim PET scores in a threat mannequin, the crew discovered that, at a cut-off rating of 0.69, it was capable of determine excessive versus low threat sufferers at a hazard ratio of 8.85 (p<0.001).
They decided that the true optimistic charge with the mannequin was 67.7%, whereas the false optimistic charge was 9.5%.
Dr Linton added that, in a separate multivariate mannequin, CD22 was a major predictor of therapy failure, outlined as a PET rating of 4–5 or a cHL occasion.
No funding declared.
Linton declares Roche: Consultancy; Celgene: Membership on an entity’s Board of Administrators or advisory committees; Janssen: Different: Journey, lodging, bills ; Celgene: Different: Journey, lodging, bills; Beigene: Membership on an entity’s Board of Administrators or advisory committees; Takeda: Honoraria; Gilead: Membership on an entity’s Board of Administrators or advisory committees; Karyopharm: Membership on an entity’s Board of Administrators or advisory committees.
62nd ASH Annual Assembly and Exposition: Summary 2918. Introduced 7 December.
Blood 2020; 136 (Complement 1): 18–19. doi: 10.1182/blood-2020-136318