A negative positron emission tomography (PET)/computed tomography (CT) signal at six months is associated with improved survival outcomes in patients with newly diagnosed multiple myeloma (MM), according to study findings published in Blood Advances. Findings on magnetic resonance imaging and PET/CT have shown prognostic value, but patients are still primarily followed by biochemical methods and unexpected results are often seen.
“Heterogeneity in the biological background and clinical presentation of MM dictates a multidimensional approach in disease assessment both at diagnosis and at subsequent follow-up,” the authors wrote. “The comprehensive nature of the whole-body PET/CT evaluation can address multiple disease monitoring lapses for [patients with MM] and justifies some discrepancies between hematologic and imaging responses.”
This retrospective cohort study aimed to assess the prognostic significance of PET/CT exams six months after induction therapy and to evaluate the additive value of PET/CT in the conventional hematologic response for patients with MM after initial induction treatment. The hypothesis was that patients with a complete metabolic response on PET/CT would have prolonged time to next treatment (TTNT) and overall survival (OS) compared to those that remained stable or had moderately reduced uptake.
Researchers assessed results among 195 patients with newly diagnosed MM (median age = 61) who received a fluorodeoxyglucose (FDG) PET/CT exam with radiologic interpretation at baseline and approximately six months after diagnosis. A negative PET/CT was defined as the disappearance of every area of increased FDG uptake at baseline or decrease in uptake to less than mediastinal blood pool activity or decrease in metabolic activity to less than that of surrounding normal tissue. Patients with residual disease at the six-month mark were categorized as progressed if the PET/CT showed new areas of increased FDG metabolism or positive if the existing lesions did not entirely disappear.
Researchers also determined the hematologic response achieved at the second PET/CT. Comparisons were made for subgroups of patients with positive and negative PET/CT results. The endpoints of the study were TTNT from date of diagnosis to change or intensification of treatment and OS measured from the date of diagnosis to death from any cause.
Median follow-up of the entire cohort was 80.6 months. After initiation of treatment, the median TTNT was 24.6 months (95% CI 20.4-29.1) and the median OS was 79 months (95% CI 63.1-119.1).
Diagnostic PET/CT was negative for eight patients at baseline. At six months, 50 patients had a negative PET/CT and 145 had detectable disease. Negative PET/CT at six months was associated with prolonged median TTNT (55.2 months) compared to a positive PET/CT (25.1 months) or PET/CT with signs of progression (7 months; p<0.0001). Patients with a negative PET/CT had unreached median OS compared to 72 and 27.7 months for positive and progressive disease, respectively (p<0.0001).
When comparing negative PET/CT and all patients with positive PET/CT, including those with progression, the same significant association was seen: median TTNT was 55.2 versus 17.8 months (p<0.0001) and median OS was unreached versus 60.8 months (p<0.0001).
Evaluating the additive value of negative PET/CT to the conventional biochemical criteria, researchers found that of the 54 patients (27.7%) who attained a complete response (CR) at the time of the second PET/CT, 24 had a negative PET/CT (44.4%) compared to 30 who had a positive PET/CT (55.6%).
Patients who had both CR and negative PET/CT had a prolonged TTNT (58.9 vs. 39.2 months; p=0.27) and a significantly prolonged OS (unreached vs. 72 months; p=0.01) compared to those who had only hematologic response.
According to researchers, “these results signify true PET/CT improvement in the post-treatment setting, as only 8 patients (4.1%) of the entire cohort had a negative PET/CT at baseline. The prognostic significance of PET/CT for TTNT and OS was retained when multiple known risk factors for unfavorable outcomes were analyzed with the multivariable Cox regression model.”
Researchers concluded that PET/CT could be incorporated into the post-treatment evaluation of patients with newly diagnosed MM, as it adds crucial prognostic information in the biochemical assessment.
Study limitations included the retrospective design and significant variability of treatment regimen within the cohort.
Any conflicts of interest declared by the authors can be found in the original article.
Charalampous C, Goel U, Broski SM, et al. Utility of PET/CT in assessing early treatment response in patients with newly diagnosed multiple myeloma [published online 2022 Mar 2]. Blood Adv. doi: 10.1182/bloodadvances.2022007052.
There have been great advances in the treatment and management of MM, leading to long-term improvements in outcomes. We are now in an era of examining quadruplet-based induction regimens, based on studies like GRIFFIN1 and CASSIOPEIA,2 to improve depth of response in patients with newly diagnosed MM. As such, surrogate markers of PFS and OS are also evolving with the use of measurable residual disease (MRD) testing and the International Myeloma Working Group criteria for MRD.3
This study demonstrated the prognostic significance of PET/CT exams at six months following induction therapy. Patients that were PET/CT negative had prolonged median TTNT (55.2 months vs. 18.8 months) and OS (unreached vs. 60.8 months), compared to those that were PET/CT positive. Additionally, patients who were PET/CT negative had an increased median TTNT and OS regardless of their hematologic depth of response. The findings of this study are encouraging and highlight the value of assessing PET/CT status at six months following induction treatment for response assessment and disease prognostication.
There are limitations and need for improvement, particularly in standardizing the disease quantification and interpretation of scans. This also relates to best timing of imaging, or consideration of serial imaging, to assess disease response, as PET activity may be related to early post-treatment changes rather than residual disease. Recent introduction of PET/magnetic resonance imaging may further enhance imaging capabilities, and additional studies should be done to determine optimal imaging technique.
The incorporation of PET/CT into clinical practice adds another dimension for hematologists to evaluate baseline disease, response, and progression. Understanding the possible prognostic implications, as highlighted by this study, may also be incorporated in redefining response criteria and could affect treatment decisions based on a response-adaptive approach to treatment intensification.
Sarah Lee, MD
Seattle Cancer Care Alliance
1. Voorhees PM, Kaufman JL, Laubach J, et al. Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood. 2020;136(8):936-945.
2. Moreau P, Attal M, Hulin C, et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study. Lancet. 2019;394(10192):29-38.
3. Kumar S, Paiva B, Anderson KC, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 2016;17(8):e328-e346