Friday, May 29, 2015
Mets Day 1143: Great article re nivolumab
On the eve of the ASCO conference, the Washington Post has released an interesting article on nivolumab, discussing how it and other immune therapies are changing the course of cancer. Also included is a helpful graphic explaining how nivolumab works. There is also discussion about the cost once they are approved; I'm just happy that I'm in a clinical trial and the drug is working for me.
Thursday, May 28, 2015
Mets Day 1142: Eighth Opdivo infusion
I returned home from Utah late on Tuesday (actually early Wednesday morning) so I could get my eighth round of nivolumab. There are no clinical trial locations for my trial in Utah or anywhere else within a thousand miles, and even if there was, it is apparently almost impossible to drop in at another location and get the experimental drug. So yesterday I went in for lab work, and this morning Jennifer and I braved the Washington beltway and I 95 to Baltimore, despite the conspiracy of the traffic gods to slow our way (semi overturned on the inner loop; two accidents between DC and Charm City, etc.).
I discussed with Dr. Hahn the fact that none of the abstracts for this week's ASCO meeting (the American Society for Clinical Oncologists, starting tomorrow in Chicago) discussed nivolumab and metastatic bladder cancer. Nivolumab was discussed in relation to other cancers in 74 other papers, however, as was other immunotherapy agents, such as MPDL3280A. Dr. Hahn was familiar with the literature, as he was on an ASCO panel that would summarize the most recent science regarding immunotherapy as a weapon against cancer. He said that he would have several discussions with his colleagues and representatives from Bristol-Myers Squibb about nivolumab and mets BC, and would bring back any news regarding durability.
I also asked Dr. Hahn about the confounding disparity between the different interpretations of my CT scans. He said that he had personally measured my tumors in my last scan, and had compared them to the prior scans. He said that his measurements were in between the dimensions recorded by the radiologists. He shrugged it off, noting that variations of a few millimeters were not a big deal. The main thing, he said, was that every one agreed that my tumors were substantially smaller than they were in the prior scans.
He asked if I had noticed any side effects. Other than the left side of my neck being a little sore (which probably is from a bad night's sleep), there continues to be nothing of note. All of my labs were good - the nurse helping with my infusion said that they were better than his. While I was getting my infusion, a massage therapist came by and offered a neck and shoulder massage, which Jennifer happily accepted. The massage therapist explained that a grateful family had wanted to create a way to help ease the stress in the chemo infusion area, and worked with Johns Hopkins to fund a roving masseuse.
After I was infused with my meds, Jennifer dropped me off at BWI so I could fly back to Utah and spend more time with my newest granddaughter, as well as Rose, Josh, and Chelsea. I'll be there through June 9, then will return home for round nine. Kirsten will fly to Utah after I leave, and she will be followed by Jennifer. I guess I can't keep Lily all to myself.
While in Utah, I made a couple of visits to the LDS Family History Library, to see if I could break through some barriers in researching the genealogy of my father's ancestors. He had been orphaned at a young age, and had relatively little information about his parents or their families. I met with success, and was able to trace my dad's line back for several generations. I was able to document that my paternal grandfather was married four times (at ages 21, 25, 28, and 43, the last being to my grandmother). So far, I have not uncovered evidence that he sired any other children. He died in 1935, at age 50.
My paternal great-grandfather, by contrast, was a prominent citizen of Vancouver, British Columbia, being a barrister, member of the provincial assembly (including a stint as speaker), built the first Vancouver skyscraper in 1915, and has a mountain and glacier named after him. While he was serving in the legislature and rallying his fellow citizens during Great War, his oldest son (my grandfather) renounced his Canadian citizenship and was naturalized a US citizen.
My paternal grandmother had one son by her first husband, in 1918. She and my grandfather married in 1927, and my father was born in 1930. He was her second child. She died when he was eight. Her father was a civil engineer, born in Prussia in 1847, emigrated to the US in the 1880s, and married my great-grandmother in Colorado in 1889. My grandmother was born in 1891. Her mother was born in Bath, England, in 1860, the oldest child of a fishmonger and merchant. My great-grandfather's family had sufficient means to employ a couple of servants around the turn of the century, and take several trips back to England. At times, my great-grandfather prefixed his surname with "von", the Prussian appellation of nobility, although I can find no basis for that assertion.
These all are facts that I have teased out of documents I've discovered in the past couple of weeks. To look at documents more than a hundred years old - census records, passenger manifests, oaths of marriage and citizenship - and glean the dry bones of those long dead. What stories must be behind those records! The wrenching decision to leave their home countries and come to America, the desire to cleave from the past, to reinvent oneself: I am descended of recent immigrants, seekers of fortune, a better life.
I discussed with Dr. Hahn the fact that none of the abstracts for this week's ASCO meeting (the American Society for Clinical Oncologists, starting tomorrow in Chicago) discussed nivolumab and metastatic bladder cancer. Nivolumab was discussed in relation to other cancers in 74 other papers, however, as was other immunotherapy agents, such as MPDL3280A. Dr. Hahn was familiar with the literature, as he was on an ASCO panel that would summarize the most recent science regarding immunotherapy as a weapon against cancer. He said that he would have several discussions with his colleagues and representatives from Bristol-Myers Squibb about nivolumab and mets BC, and would bring back any news regarding durability.
I also asked Dr. Hahn about the confounding disparity between the different interpretations of my CT scans. He said that he had personally measured my tumors in my last scan, and had compared them to the prior scans. He said that his measurements were in between the dimensions recorded by the radiologists. He shrugged it off, noting that variations of a few millimeters were not a big deal. The main thing, he said, was that every one agreed that my tumors were substantially smaller than they were in the prior scans.
He asked if I had noticed any side effects. Other than the left side of my neck being a little sore (which probably is from a bad night's sleep), there continues to be nothing of note. All of my labs were good - the nurse helping with my infusion said that they were better than his. While I was getting my infusion, a massage therapist came by and offered a neck and shoulder massage, which Jennifer happily accepted. The massage therapist explained that a grateful family had wanted to create a way to help ease the stress in the chemo infusion area, and worked with Johns Hopkins to fund a roving masseuse.
After I was infused with my meds, Jennifer dropped me off at BWI so I could fly back to Utah and spend more time with my newest granddaughter, as well as Rose, Josh, and Chelsea. I'll be there through June 9, then will return home for round nine. Kirsten will fly to Utah after I leave, and she will be followed by Jennifer. I guess I can't keep Lily all to myself.
While in Utah, I made a couple of visits to the LDS Family History Library, to see if I could break through some barriers in researching the genealogy of my father's ancestors. He had been orphaned at a young age, and had relatively little information about his parents or their families. I met with success, and was able to trace my dad's line back for several generations. I was able to document that my paternal grandfather was married four times (at ages 21, 25, 28, and 43, the last being to my grandmother). So far, I have not uncovered evidence that he sired any other children. He died in 1935, at age 50.
My paternal great-grandfather, by contrast, was a prominent citizen of Vancouver, British Columbia, being a barrister, member of the provincial assembly (including a stint as speaker), built the first Vancouver skyscraper in 1915, and has a mountain and glacier named after him. While he was serving in the legislature and rallying his fellow citizens during Great War, his oldest son (my grandfather) renounced his Canadian citizenship and was naturalized a US citizen.
My paternal grandmother had one son by her first husband, in 1918. She and my grandfather married in 1927, and my father was born in 1930. He was her second child. She died when he was eight. Her father was a civil engineer, born in Prussia in 1847, emigrated to the US in the 1880s, and married my great-grandmother in Colorado in 1889. My grandmother was born in 1891. Her mother was born in Bath, England, in 1860, the oldest child of a fishmonger and merchant. My great-grandfather's family had sufficient means to employ a couple of servants around the turn of the century, and take several trips back to England. At times, my great-grandfather prefixed his surname with "von", the Prussian appellation of nobility, although I can find no basis for that assertion.
These all are facts that I have teased out of documents I've discovered in the past couple of weeks. To look at documents more than a hundred years old - census records, passenger manifests, oaths of marriage and citizenship - and glean the dry bones of those long dead. What stories must be behind those records! The wrenching decision to leave their home countries and come to America, the desire to cleave from the past, to reinvent oneself: I am descended of recent immigrants, seekers of fortune, a better life.
Friday, May 22, 2015
Mets Day 1136: More analysis of my May 5 CT scan: CR?
Last week Dr. Aygun at Johns Hopkins did a supplemental interpretation of my May 5 CT scan of my neck. It was posted on May 17, but I've been visiting family in Utah since May 14, and between my niece's wedding and the birth of my granddaughter, I didn't notice it until yesterday. Here's the text of the report (I've added hyperlinks):
In addition, Dr. Idowu, the radiologist who initially read the May 5 scan, looked at tumors on the left side of my neck at levels 3 and 4. Dr. Idowu wrote that the left level 3 lymph node previously measuring 1.5 x 1.1 cm currently measures 1.4 x 0.8 cm. Dr. Aygun did not measure that level 3 node, and simply wrote that there were no non-target lesions. How could a tumor be measured to be 1.4 x 8 mm by one doctor simply be missed by the second doctor?
Dr. Aygun has concluded that I have had "CR": a complete response (in the neck). But when I asked Dr. Hahn the same question at my last visit, he told me that it was too soon to say that I had a complete response, although he agreed that the short axis of my tumors was under 1.0 cm, so they were not "pathological" under the RECIST 1.1 guidelines. But he was unwilling to go as far as Dr. Aygun.
Although Dr. Aygun's reading would ordinarily be great news, I have a healthy level of skepticism over the results. I'll be asking Dr. Hahn some questions about this at my next appointment on May 28.
RESULT: This report is dictated with specific measurement of index lesions as RECIST 1.1. Longest unidimensional measurement in mm for non-nodal disease. Short axis measurements for nodes.
Please see the original clinical report of the CT scan of the neck from 5/5/2015.
COMPARISON: 3/24/2015.Dr Aygun's results are dramatically different than the original interpretation of my May 5 scan by Dr. Idowu. In the initial results, Dr. Idowu wrote that "the left level 4 lymph node previously measuring 1.3 x 0.9 cm currently measures 1.3 x 0.7 cm." But according to Dr. Aygun's supplemental read, the left level 4 node previously was 7 x 9 mm (not 1.3 x 9 cm), and now measures 5 x 5 mm (not 1.3 x 7 cm). I do not understand how two different radiologists, looking at the exact same image, can conclude that the same tumor is either 1.3 x 0.7 cm, or 5 x 5 mm. That's a 50% difference!
TARGET LESIONS:
TL1: Left level 5 lymph node measures 5 x 5 mm at slice position 335.7 compared to 9 x 12 mm previously.
TL2: Left level 4 lymph node measures 5 x 5 mm at slice position 362.7 compared to 7 x 9 mm previously.
NON-TARGET LESIONS: None
NEW LESIONS: None
IMPRESSION: CR (in the neck). All nodal target lesions are less than 10 mm.
In addition, Dr. Idowu, the radiologist who initially read the May 5 scan, looked at tumors on the left side of my neck at levels 3 and 4. Dr. Idowu wrote that the left level 3 lymph node previously measuring 1.5 x 1.1 cm currently measures 1.4 x 0.8 cm. Dr. Aygun did not measure that level 3 node, and simply wrote that there were no non-target lesions. How could a tumor be measured to be 1.4 x 8 mm by one doctor simply be missed by the second doctor?
Dr. Aygun has concluded that I have had "CR": a complete response (in the neck). But when I asked Dr. Hahn the same question at my last visit, he told me that it was too soon to say that I had a complete response, although he agreed that the short axis of my tumors was under 1.0 cm, so they were not "pathological" under the RECIST 1.1 guidelines. But he was unwilling to go as far as Dr. Aygun.
Although Dr. Aygun's reading would ordinarily be great news, I have a healthy level of skepticism over the results. I'll be asking Dr. Hahn some questions about this at my next appointment on May 28.
Monday, May 18, 2015
Mets Day 1132: A second granddaughter
I flew to Utah on May 14 for the wedding of my niece, and to await the birth of my second granddaughter to Chelsea and Josh. Chelsea went into labor early this morning, and this afternoon gave birth to Lily, 7 lbs 10 oz, 19" long, and absolutely beautiful. I had brought Rose to the hospital in the morning, then took her home for her nap while Chelsea had a fast and painless (2 push) delivery. After Rose awoke, I said, "Do you want to go see Lily?" and she shouted "Yes!"
Introducing Rose to her little sister was one of the most tender and beautiful things I have seen. Rose gently kissed her sister's cheek and was very interested in making sure Lily's hat was on. Rose kept looking over at her mom to make sure the baby wasn't still inside. Eventually, I rocked Lily while Chelsea and Josh spent time with Rose, playing and talking with her. Rose has no idea that her solar system has just added a second sun.
When I held Lily, I was amazed and humbled at how this tiny person was created. I believe that Lily, like all humans, have a spirit that was with God before birth. As Wordsworth wrote in Intimations of Immortality:
I am so grateful that my life has been prolonged to see this day. I know that it is not through my actions that I survive against the odds: the clinical trial that is working on my cancer does not have the same effect on all metastatic bladder cancers (see this post for an example). I simply give thanks for each day, and find joy and rejoicing in my posterity.
Introducing Rose to her little sister was one of the most tender and beautiful things I have seen. Rose gently kissed her sister's cheek and was very interested in making sure Lily's hat was on. Rose kept looking over at her mom to make sure the baby wasn't still inside. Eventually, I rocked Lily while Chelsea and Josh spent time with Rose, playing and talking with her. Rose has no idea that her solar system has just added a second sun.
When I held Lily, I was amazed and humbled at how this tiny person was created. I believe that Lily, like all humans, have a spirit that was with God before birth. As Wordsworth wrote in Intimations of Immortality:
- Our birth is but a sleep and a forgetting:
- The Soul that rises with us, our life's Star,
- Hath had elsewhere its setting,
- And cometh from afar:
- Not in entire forgetfulness,
- And not in utter nakedness,
- But trailing clouds of glory do we come
- From God, who is our home:
- Heaven lies about us in our infancy!
I am so grateful that my life has been prolonged to see this day. I know that it is not through my actions that I survive against the odds: the clinical trial that is working on my cancer does not have the same effect on all metastatic bladder cancers (see this post for an example). I simply give thanks for each day, and find joy and rejoicing in my posterity.
Tuesday, May 12, 2015
Mets Day 1126: Seventh Opdivo infusion
Things I've learned from today's infusion of nivolumab through my clinical trial at Johns Hopkins:
1. Getting my lab work done the day before saves at least two hours on infusion day at Hopkins.
2. My port (over 3 years old) does not like to return blood. It takes infusions just fine, but when nurses try to draw blood through it, the tip of the port apparently buries itself into the tissue of the vein, blocking blood draws. Almost every time I've gone in, there have been some issues with my port. Today I got my infusion through an IV while a clot-busting drug was shoved into my port to dissolve whatever was precluding getting a return.
3. According to Dr. Hahn, it's too soon to say that I have had a complete response, even though my recent CT scan showed that all of my tumors had shrunk to under 1 cm in size. Dr. Hahn said that the line between a partial response and a complete response is a fuzzy one, but because my scan still detected the presence of tumors, I'm still waiting for a CR.
4. There is still no published data on nivolumab on metastatic bladder cancer. But Dr. Hahn expects to see some new data at this month's annual meeting of ASCO in Chicago. Stay tuned for updates.
5. Bristol Myers Squibb has just announced a new Phase II trial for nivolumab in metastatic bladder cancer. Apparently it's been getting enough favorable reports from my trial that the company is moving forward with getting FDA approval for mets BC.
6. The plan is to stay the course and continue getting treatments for a while.
1. Getting my lab work done the day before saves at least two hours on infusion day at Hopkins.
2. My port (over 3 years old) does not like to return blood. It takes infusions just fine, but when nurses try to draw blood through it, the tip of the port apparently buries itself into the tissue of the vein, blocking blood draws. Almost every time I've gone in, there have been some issues with my port. Today I got my infusion through an IV while a clot-busting drug was shoved into my port to dissolve whatever was precluding getting a return.
3. According to Dr. Hahn, it's too soon to say that I have had a complete response, even though my recent CT scan showed that all of my tumors had shrunk to under 1 cm in size. Dr. Hahn said that the line between a partial response and a complete response is a fuzzy one, but because my scan still detected the presence of tumors, I'm still waiting for a CR.
4. There is still no published data on nivolumab on metastatic bladder cancer. But Dr. Hahn expects to see some new data at this month's annual meeting of ASCO in Chicago. Stay tuned for updates.
5. Bristol Myers Squibb has just announced a new Phase II trial for nivolumab in metastatic bladder cancer. Apparently it's been getting enough favorable reports from my trial that the company is moving forward with getting FDA approval for mets BC.
6. The plan is to stay the course and continue getting treatments for a while.
Wednesday, May 6, 2015
Mets Day 1120: Second clinical trial scan shows good results
Yesterday I had my second CT scan as part of the nivolumab clinical trial. This scan took place after I had received six of the experimental infusions, or 12 weeks after I started the trial. The first scan showed that my targeted tumors had shrunk by 50%. This scan showed that the tumors continued to shrink, although not at the same rate. Here's the key language from the neck scan:
The only bad news is that, according to the neck scan, I am 82 years old (the abdomen and chest scan had my age correctly noted). I emailed the clinical trial nurse and said that she'd have to report accelerated neck aging as one of the side effects of the study. Her response: "I love your attitude and sense of humor."
I'll go in next week for my seventh infusion, and will talk with Dr. Hahn about the durability of the nivolumab therapy. As far as I can tell, there is no publicly released data regarding the durability of nivolumab on metastatic bladder cancer patients. Nivolumab was first tested on metastatic melanoma. A March 2014 report found that the results were durable for two or more years, and that some patients had ongoing beneficial effects even after stopping therapy. A September 2014 report on the use of nivolumab on metastatic renal cell carcinoma also found durable results, with the best results going to those who stayed on the drug. A November 2014 follow-up report on metastatic melanoma patients receiving nivolumab showed ongoing durability, with a median follow-up of 55 months, which according to the report "is the longest follow-up of an anti-PD-1 agent done to date." That report also said that, of the the patients who had an overall response, more than half were maintaining that overall response. And a April 9, 2015 review of immunotherapy trials published by the British Cancer Journal found that
1. Nivolumab is an effective immunotherapy agent on my metastatic bladder cancer.
2. I have had an objective response -- specific, measurable results -- as a result of the nivolumab.
3. I am continuing to see tumor shrinkage as a result of the nivolmab.
4. This last scan likely has put me in the category of a complete response, meaning that my metastatic tumors have shrunk to under 1 cm in size on the short axis.
5. I still have measurable disease, however, so I not yet at NED (no evidence of disease).
6. I should continue with the nivolumab as long as possible, since that is what has provided the best results to patients taking nivolumab for other cancers. So that means no trips away from Hopkins for more than two weeks. I can live with that.
Findings: Although possibly due to variation in slice selection and patient positioning, there is slight interval decrease in the size of the left level 3 lymph node as demonstrated on image 569 of series 4, now measuring 1.4 x 0.8 cm (previously 1.5 x 1.1 cm). The left level 4 lymph node previously measuring 1.3 x 0.9 cm currently measures 1.3 x 0.7 cm. Other smaller lymph nodes are either unchanged or smaller compared to the prior examination in the bilateral neck. There is no new lymphadenopathy. No mass or pathologic fluid collection is identified in the neck.The scans of the chest and abdomen found no new tumors. The supraclavicular node is now "subcentimeter" in size and is "stable." There is no evidence of pulmonary embolisms, either. So the bottom line is that, in the past six weeks, the two target tumors shrunk by another 25%. Yay!
The only bad news is that, according to the neck scan, I am 82 years old (the abdomen and chest scan had my age correctly noted). I emailed the clinical trial nurse and said that she'd have to report accelerated neck aging as one of the side effects of the study. Her response: "I love your attitude and sense of humor."
I'll go in next week for my seventh infusion, and will talk with Dr. Hahn about the durability of the nivolumab therapy. As far as I can tell, there is no publicly released data regarding the durability of nivolumab on metastatic bladder cancer patients. Nivolumab was first tested on metastatic melanoma. A March 2014 report found that the results were durable for two or more years, and that some patients had ongoing beneficial effects even after stopping therapy. A September 2014 report on the use of nivolumab on metastatic renal cell carcinoma also found durable results, with the best results going to those who stayed on the drug. A November 2014 follow-up report on metastatic melanoma patients receiving nivolumab showed ongoing durability, with a median follow-up of 55 months, which according to the report "is the longest follow-up of an anti-PD-1 agent done to date." That report also said that, of the the patients who had an overall response, more than half were maintaining that overall response. And a April 9, 2015 review of immunotherapy trials published by the British Cancer Journal found that
The most extensive clinical experience with PD-1 antibodies has been obtained with both nivolumab and pembrolizumab, which have demonstrated highly durable response rates with acceptable toxicity in large phase I studies involving patients with advanced melanoma, NSCLC, renal cell carcinoma (RCC) and Hodgkin’s disease . . . .None of these reports were specific to bladder cancer, however. Although there are a number of reports noting the fact that nivolumab is being tested on mets bladder cancer patients, I have not been able to locate any data on the durability on my type of cancer. The best I can do is to extrapolate from the data from other cancers. From what I've been able to gather, here are the conclusions that I am drawing:
1. Nivolumab is an effective immunotherapy agent on my metastatic bladder cancer.
2. I have had an objective response -- specific, measurable results -- as a result of the nivolumab.
3. I am continuing to see tumor shrinkage as a result of the nivolmab.
4. This last scan likely has put me in the category of a complete response, meaning that my metastatic tumors have shrunk to under 1 cm in size on the short axis.
5. I still have measurable disease, however, so I not yet at NED (no evidence of disease).
6. I should continue with the nivolumab as long as possible, since that is what has provided the best results to patients taking nivolumab for other cancers. So that means no trips away from Hopkins for more than two weeks. I can live with that.
median
follow-up is 55 months, which represents the longest follow-up of an
anti-PD-1 agent done to date,” - See more at:
http://www.ajmc.com/conferences/SMR2014/Nivolumab-Shows-Durable-Response-in-Heavily-Pre-treated-Patients-with-Advanced-Melanoma#sthash.RLZL9hR2.dpuf
median
follow-up is 55 months, which represents the longest follow-up of an
anti-PD-1 agent done to date,” - See more at:
http://www.ajmc.com/conferences/SMR2014/Nivolumab-Shows-Durable-Response-in-Heavily-Pre-treated-Patients-with-Advanced-Melanoma#sthash.RLZL9hR2.dpuf
median
follow-up is 55 months, which represents the longest follow-up of an
anti-PD-1 agent done to date,” - See more at:
http://www.ajmc.com/conferences/SMR2014/Nivolumab-Shows-Durable-Response-in-Heavily-Pre-treated-Patients-with-Advanced-Melanoma#sthash.RLZL9hR2.dpuf
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