Impact of PET-CT Response on Survival Parameters Following Autologous Stem Cell Transplantation Among Patients with Multiple Myeloma: Comparison of Two Cut-Off Values

Abstract

Background and Aim: PET is a useful tool that allows deeper assessment of response beyond that measured by M protein levels. It has been reported to predict outcome following both ASCT and recently non-transplant setting too. To be able to integrate PET-CT negativity to internationally accepted response criteria the cut-off level needs to be validated by independent investigators. This prospective study was initiated to elucidate the prognostic role of PET-CT in the ASCT setting testing the cut-off level 4.2 initially reported by Zamagniet al versus the cut-off (3.35) based on our results. Patients and Methods: 139 consecutive patients diagnosed and transplanted in Ankara University with pre- and post-transplant (Tx) PET-CT imaging were included. Patients were: Median age 56.5 +/- 8.7 (M/F: 79/60), ISS I/II/III: 50/55/34, renal impairment (10.8%), bone involvement (90.6%), del13q (40.9%), t(4;14) and/or p53(26.5%), LDH high(12.9%), induction with Bortezomib (73.4%). Pre-Tx clinical response ³VGPR: 52.9%, post-Tx clinical response ³VGPR: 77.5%. Overall Survival (OS): median: 33 months (4.2-141 months). PASW statistics for Windows program was used for statistical analysis. Results: ROC analysis revealed 3.35 as a significant cut-off level (p=0.005; OS). PET-CR was defined FDG uptake less than 4.2 or 3.35 depending on the analysis. Pre-Tx PET-CR:17.4%, post-Tx PET-CR: 69.6% (<4.2), 46.4% (<3.35). Cross tabulation of post-Tx clinical response versus PET response is summarized in Table 1. PET (>4.2) was predictive for PFS (p=0.05) but not OS (p=0.096). However PET (>3.35) was predictive for OS (p=0.037) but not PFS. PET (>4.2) was predictive for OS (p=0.014) and PFS (p=0.019)among only ³VGPR patients. Similarly PET (>3.35) among ³VGPR patients was also predictive for OS (p=0.05) and PFS (p=0.04). PET-CR was not predictive among ³CR patients significantly. Cox regression analysis for PFS, when PET (>4.2) is used, ISS was significant only (OR: 1.99, p=0.049) when post-Tx clinical response (OR: 0.46, p=0.022) is not included in the model. For OS, clinical response both pre-Tx (OR: 0.35, p=0.015) and post-Tx (OR: 0.18, p<0.001) is the only significant parameter. PET (>3.35) increased the predictive value of PET. In addition to clinical response, PET-CR appeared as a borderline significant factor for OS: pre-Tx (OR: 2.2, p=0.078), post-Tx (OR: 2.26, p=0.067). In conclusion both PET (<4.2) and PET (<3.35) recognizes deeper responses as manifested by extension of PFS (PET<4.2) and OS (PET<3.35). Both assessments were able to define patients with separate survival outcomes within the ³VGPR group. This effect could not be confirmed within the ³CR group due to the relatively smaller sample size. After multivariate analysis only PET (>3.35) approached significance. To be able to integrate PET-CR to response criteria definition of PET-CR needs to be confirmed. Table 1PET cut-off 4.2PET cut-off 3.35Number of patientsnegativepositivenegativepositive<PR2020PR155911VGPR39143122CR22141521< VGPR17511113 VGPR61284643< CR561942333 CR221415213 year PFS45.8%25.6%48.9%28.9%3 year OS91.6%76.1%94.9%79.5% Figure-1: PET(<3.35) and OS Figure-1:. PET(<3.35) and OS Figure-2. PET(<3.35) and OS within the ³VGPR patients Figure-2. PET(<3.35) and OS within the ³VGPR patients Disclosures No relevant conflicts of interest to declare.

PET Molecular Imaging: A Holistic Review of Current Practice and Emerging Perspectives for Diagnosis, Therapeutic Evaluation and Prognosis in Clinical Oncology

“…However, its limited value in assessing the response to treatment and the time-consuming whole-body acquisition protocols have promoted the use of 18 F-FDG PET/CT as a fast-whole-body complement imaging modality to manage patients with MGUS and multiple myeloma. In comparison with MRI, 18 F-FDG PET/CT shows faster normalization of image findings [ 74 ]. Recently, the International Myeloma Working Group has integrated 18 F-FDG PET/CT into the diagnostic criteria of multiple myeloma, considering abnormal bone 18 F-FDG uptake as a C.R.A.B feature (C = hypercalcemia; R = renal failure; A = anemia; and B = bone lesions) [ 75 ].…”

Positron Emission Tomography (PET) Imaging of Multiple Myeloma in a Post-Treatment Setting

“…On the other hand, PET sensibility can be hampered by elevated glycemic levels, high-dose steroid therapy, low hexokinase-2 expression [ 52 , 53 ] or the presence of pure lytic lesions characterized by a low FDG uptake or an early PET-positive lesion without a correspondent osteolytic area. Furthermore, the spatial resolution of PET imaging could be insufficient to detect the typical salt and pepper Bone Marrow (BM) infiltration or to identify the occurrence of small lytic lesions in specific anatomic districts (such as the skull with the close brain physiological activity), generating possible misinterpretations [ 54 ].…”

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“…Changes in FDG avidity occur earlier than do structural modifications seen with skeletal survey, CT, and MRI conventional sequences. Therefore, PET/CT is the best tool for posttreatment evaluation (Fig 5) according to the results of several studies (53)(54)(55) and the International Myeloma Working Group (25).…”

“…Patients who have metabolically active lesions at PET/CT after treatment but reductions in lesion size, number, and radiotracer uptake are referred to as imaging partial responders. More than three persistent focal lesions, higher SUVs, or extramedullary disease is associated with a worse prognosis (Fig 12) (25,54,55).…”