Krd Consolidation Abrogates Poor Prognosis of FDG PET/CT Positivity after ASCT: Results from a Phase II Study (CONPET)

Background

[18F]-Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) positivity after first line treatment with autologous stem cell transplantation (ASCT), is strongly correlated with reduced progression free survival (PFS) and overall survival (OS) (Moreau et al., JCO, 2017). However, FDG PET/CT positive patients who obtain FDG PET/CT negativity after treatment seem to have comparable outcomes to patients who were FDG PET/CT negative at baseline (Davies et al., Haematologica 2018). The prognostic impact of FDG PET/CT is complementary to the impact of minimal residual disease (MRD) as patients who are MRD negative and FDG PET/CT positive, have an inferior survival compared to patients who are both MRD and FDG PET/CT negative (Alonso et al., AJH 2019). However, prospective studies comparing FDG PET/CT and MRD are lacking, and the use of FDG PET/CT as an indication for additional treatment has not been studied before. We have previously reported primary endpoint results from the CONPET-trial (Nørgaard et al., Leukemia 2023). In this abstract, we will report results on PFS and OS.

Methods

CONPET was a prospective phase II, open-label clinical trial (NCT03314636). Patients were eligible for the trial if they had received first line treatment including ASCT and were in very good partial response (VGPR) or better. Patients who were FDG PET/CT positive defined by the Italian Myeloma criteria for PET USe (IMPETUS) (Nanni C et al., EJNMMI 2016 and 2018) were included in the treatment phase of the study. Treatment consisted of four 28-day cycles of KRd (carfilzomib 36 mg/m² day 1,2,8,9,15 and 16 (except 20 mg/m² day 1 and 2 first cycle), lenalidomide 25 mg day 1-21 all cycles and dexamethasone 40 mg day 1,8,15 and 22 all cycles). FDG PET/CT was repeated after treatment. Patients were also assessed for MRD by Euroflow (sensitivity: 10^-5) before and after treatment. Patients who were FDG PET/CT negative at screening, did not receive KRd consolidation treatment but standard post ASCT-treatment according to local guidelines.

Primary endpoint results were published in 2023: Fifty-three patients of 159 (33%) had a positive FDG PET/CT result. Forty-eight patients completed KRd treatment. Sixteen patients (33%) converted into FDG PET/CT negativity, while 32 (67%) remained FDG PET/CT positive. A higher proportion converted into FDG PET/CT negativity in patients who were MRD negative before KRd treatment. Twenty-eight of 49 (57%) patients with a FDG PET/CT positive result were MRD negative before KRd consolidation, whereas 78% of patients were MRD negative after treatment with KRd.

Results

With a median follow-up of 47.5 months, the median PFS was not different between FDG PET/CT positive patients treated with four cycles of KRd, and FDG PET/CT negative patients (53.5 months versus 52.4 months, p = 0.678).

The median OS was not reached in either group. The 4-year OS was 93% (95% CI 86%-97%) in the FDG PET/CT negative group and 83% (95% CI 69%-91%) in the FDG PET/CT positive group.

Patients who were MRD negative after treatment, had significantly longer PFS than patients who were MRD positive after treatment (Not reached (NR) vs 18.7 months, p=0.002).

In patients who were MRD negative after KRd treatment, FDG PET/CT positive and FDG PET/CT negative patients had similar PFS (NR vs NR, p = 0.740).

In patients who were both FDG PET/CT and MRD positive after treatment, the median PFS was 5.3 months. In patients who were FDG PET/CT negative and MRD positive after treatment, the median PFS was 45.6 months. In patients who were FDG PET/CT positive and MRD negative, the median PFS was 53.5 months. In patients who were both FDG PET/CT negative and MRD negative, the median PFS was NR.

The median OS was not reached in any group after KRd treatment.

Conclusion:

In this prospective clinical trial, patients who were FDG PET/CT positive after ASCT and received KRd consolidation treatment had similar PFS compared with patients who were FDG PET/CT negative and received standard of care post-ASCT treatment (len maintenance). The adverse prognostic impact of a positive FDG PET/CT reported in previous studies may have been abrogated by KRd treatment. Patients who are both FDG PET/CT and MRD positive have poor prognosis.