Praying this may be the answer for my husband who was just told 2 days ago that there's nothing to do, since his marrow isn't working after his 4th Xofigo treatment (see earlier posts below)!!
Exceptional Response to Pembrolizumab in a Patient With Castration-Resistant Prostate Cancer With Pancytopenia From Myelophthisis: A Case Report
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Panagiotis J. Vlachostergios, MD, PhD; Julia T. Geyer, MD; John Miller, MD; Rebecca Kosloff, MD; Himisha Beltran, MD; and Scott T. Tagawa, MD
Journal of Oncology Practice
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Below is the abstract of the article. The full journal article is available to read for free on MedPage Today - click here or in the link below
Introduction
Myelophthisis is a type of bone marrow failure resulting from infiltration by cancer cells and manifests with peripheral cytopenias. Although rare in metastatic solid tumors, lung, breast and prostate are the most commonly associated primaries. Besides transfusion support, little is known about the efficacy of systemic therapies in such patients. The condition itself may be a barrier to optimal dosing of cytotoxic chemotherapeutics.
Metastatic castration-resistant prostate cancer (CRPC) remains lethal despite recent therapeutic advances. Although a survival benefit led to the U.S. Food and Drug Administration approval of the cell-based cancer immunotherapy sipuleucel-T in patients with asymptomatic CRPC with nonvisceral metastases, all other randomized trials of immunotherapy have been negative to date, and prostate cancer is believed to be a relatively immunologically "silent" tumor with respect to immune checkpoint inhibitors. The anti–programmed death-1 (PD-1) checkpoint inhibitor pembrolizumab was recently approved for unresectable or metastatic solid tumors characterized by high microsatellite instability or mismatch repair (MMR) deficiency, including prostate cancer.
Up to half of patients with metastatic prostate cancer and germline and/or somatic MMR mutations may experience significant responses to PD-1 inhibition; however, more data are still needed. Herein, we describe a patient with MMR-deficient metastatic CRPC with widespread metastases involving the bone marrow causing myelophthisis, who responded to pembrolizumab.
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Exceptional Response to Pembrolizumab in a Patient With Castration-Resistant Prostate Cancer With Pancytopenia From Myelophthisis: A Case Report
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JLS1
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I'm on record as being the single patient worldwide with CRPC that has had a Complete Durable Clinical Remission currently with Checkpoint Inhibitors Blockade immunotheraphy..47 infusions over past 4 years of Pembrolizimab.
There has been a large amount of data on immunotherapies in a large variety of settings, and prostate cancer has not been a particularly well-studied malignancy. The reason is that, other than mismatch repair and MSI-high, the indications have been a little bit unclear. In this trial, the authors took, essentially, unselected patients with metastatic prostate cancer, and they divided them up into a couple of groups, and then treated the patients to get an idea about the number of responders. They ended up treating 260 patients, which is a good number, and they looked at things that are potentially important (eg, PD-L1 positivity/ negativity in their assays, bones in a clear cohort), and they found that the response rate (when they combined cohorts one, two, and three) was about 6% for PSA response and the disease control rate was about 12%, and that, I think, is very, very valuable information because nobody really knew what these data looked like before this trial. Now, you can say that those numbers are so low that they’re not meaningful; but, in fact, I think there is meaning in this number because a number of groups, including ours at one point, had been trying to treat these people without an understanding of what are the biomarkers for a response. Well. It turns out that PD-L1 is not a particularly good marker in this disease, and I guess that’s not so much of a surprise.
Now, jumping ahead for a brief moment, let’s ask about what we think is true about individuals with prostate cancer and their responsiveness to immunotherapy. We do have some data with mismatch repair, which would be MLH1, MLH2, MLH6, and PMS2, and the MSI-high population. And there it’s a little bit hard to get exact numbers, but we’ll simply say that clearly those patients can be responsive. And then there’s a large subset, and I say large, probably 6% of patients or so, who have CDK12 biallelic changes in their somatic genomic analysis, and those with CDK12 biallelic changes are clearly more likely to respond. There’s a manuscript submitted now that would suggest that that response rate might be in the 30% range, and that is important to note because CDK12 has not previously been seen as an actionable mutation. So CDK12 matters and mismatch repair genes matter.
Now, there were a couple of patients in here that are mentioned in the results section, and they had 2 responding patients whose responses lasted for more than 2 years, and 1 of these patients had an amplified PD-L1 locus, which is something that has not ordinarily been linked to responsiveness. Actually, it’s an amplified CD274 locus, which includes PD-L1. The other patient had a higher tumor mutational burden, but not MSI-high. That might be from a polymerase epsilon mutation, which can have a high mutational burden, but not high MSI. So as we go forth, we now know, in all likelihood, that giving pembrolizumab across the board is not going to be associated with much response rate, but we also know that mismatch repair, high MSI, high tumor mutational burden, and amplified PD-L1,and biallelic CDK12 are all biomarkers that predict responsiveness to PD-1 inhibition. When taken in total, this manuscript, combined with other data, represents an important step forward.
Just wish our oncologist would at least consider going outside the box. He's being very discouraging. He said there's a still a small chance the bone marrow issue is due to the xofigo, not the cancer, which is why he'll continue giving transfusions as needed.
We did the Guardiant test 5+ months ago, before the change of treatment (went off Lynparza in order to prepare for xofigo, and switched steroids from prednisone to dexamethasone to extend zytiga). MO said the Guardiant test didn't provide any useful results. Why not do the test again to see if we might get different results, or why not run the FoundationOne test? I've read it's not unusual to get 2 different results if you run both tests, or if you run the same test again.
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