For anyone interested in expanding their knowledge about pseudoprogression and oncolytic viruses, it is worth having a read of this journal article on T-VEC from 2017:
Imaging Manifestations of Pseudoprogression in Metastatic Melanoma Nodes Injected with Talimogene Laherparepvec: Initial Experience - PMC (nih.gov)
Key Points:SUMMARY:Talimogene laherparepvec is an oncolytic virus recently approved for targeted treatment of advanced melanoma. Because of an inflammatory reaction, treated lesions may increase in size and develop infiltrative margins that can be construed as disease progression or extracapsular spread. In this report, we describe our initial experience imaging the response of metastatic nodes injected with talimogene laherparepvec. Six of 12 nodes (50%) showed growth from baseline followed by decreased size, 5 of 12 nodes (42%) showed a downward size trend, and 1 node showed continued increase in size. Seven of 9 nodes (78%) developed infiltrative margins at a median of 79 days, and 6 of 9 (67%) nodes became necrotic at a median of 76 days after injection, all showing decreased size at final follow-up. An increase in the size of nodes injected with talimogene laherparepvec does not necessarily indicate progression. Infiltrative margins are also frequently seen and may be confused with extracapsular disease.
CONCLUSIONS
In summary, half of the nodes in our patients showed an initial increase (pseudoprogression) in size after T-VEC injection followed by decreased size and, in some cases, resolution of the lesion. The development of infiltrative margins and necrosis was frequent, and all such nodes showed a final size that was smaller than baseline, a presumed measure of success. These imaging manifestations are concordant with the expected biologic behavior of lesions treated with immunotherapeutic agents, and necrosis appears to be common and prominent after T-VEC injection. Increased size per se is not necessarily indicative of progression or an indication to stop treatment in clinically stable patients. Additional studies with a larger number of patients are needed to fully understand the radiographic progression and magnitude of these changes and the relative contribution of both targeted and systemic immunotherapies. Because the use of targeted agents is a fairly new development and not as of yet widespread, many head and neck radiologists may not be aware of these potential imaging findings. The recognition that a patient may be undergoing such treatments is paramount to avoid diagnostic pitfalls and confusion with extracapsular spread or progression of disease. Our preliminary results highlight the importance of being cognizant of specific treatments before image interpretation.
| Tableshows a brief comparison of WHO, RECIST v1.0 and RECIST v1.1 criteria[5,6,8,11,12]. The best overall response is a result of a combination of tumor responses in target and nontarget lesions. If there is any new lesion, the overall best response is always PD. In the absence of any new lesion, CR is the complete disappearance of all target and nontarget lesions. No change in nontarget lesions reduces a CR in target lesions to an overall PR, but no change in nontarget lesions does not reduce a PR in target lesions. |
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For those that are interested in reading an official journal article in relation to what PD, iUPD, iCPD, SD, PR, CR mean, have a read of this:
iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics - PMC (nih.gov)
Here's the graph where those terms were used:
@Mason14 made this comment about the graph:
"There are currently 3 patients in cohort 4 with suspected immune-related unconfirmed progressive disease (iUPD)."
However, he failed to mention this caveat:
They used both RECIST v1.1 and iRECIST criteria. So, anything marked as a PD or SD was assessed using iRECIST otherwise they would have marked them as iUPD or iCPD. On that basis, it is inaccurate to conclude that anything marked as PD or SD could not have been as a result of pseudoprogression; it may have been pseudoprogression but also, it may not.
Finally, anyone looking for further comment on pseudoprogression in the MAST trial should refer back to the 6/11/2023 ASX release:
ASX:IMU - Phase 1 CF33 VAXINIA Study Update - Positive Early Signals (imugene.com)
| Notably one patient with bile duct cancer, treated IT with mid-dose level displayed pseudoprogression (see below) with a 49% increase in tumour burden after two cycles of therapy. However, by the 4th cycle they achieved a Complete Response (iCR) with no known recurrence in over 200 days. A second patient with bile duct cancer, who previously progressed on prior drug therapies, achieved Stable Disease (SD) for > 4months upon receiving IV-administered CF33-hNIS. Bile duct cancers are difficult to treat and typically respond poorly to immunotherapy drugs. Pseudoprogression is a phenomenon in which the cancer initially appears to be growing, largely due to the cancer cells being infected by the virus then followed by infiltration of cancer fighting immune cells. However, it is usually followed by a decrease in tumour burden when the therapy takes effect. This phenomenon can benefit patients receiving immunotherapy but often leads to premature discontinuation of treatment owing to the false impression the cancer is growing. |
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Until we have further follow up data, preferably including reference to how long since each patient commenced treatment so we can determine if they've past the point where pseudoprogression could occur, it is not possible for us to definitely assess if PD, iUPD and SD is the result of pseudoprogression or actual progression.
Currently, perhaps, our best guidance should come from the FDA granting Fast Track Designation for Vaxinia against Bile Duct Cancer. They almost certainly would have more data provided to them that what has been made public and they almost certainly would not have granted the designation if they believed the complete response was an anomaly. If the FDA assessed the data as being good enough to grant Fast Track Designation, it's good enough for me to think the trial is progressing positively. All we can really do from here is wait until the next round of results are made available.
(20min delay)
