clinical cases
Started by redeyelopez
Not asking a question about a case, just noting that I have 3 new extramedullary plasmacytomas on my schedule today.
I work in a town of <10K people and our catchment area (6 counties) is only a little over 100K. Plasmacytoma incidence in the US is 0.3-0.4/100000. That's 10x the expected rate, just today.
I work in a town of <10K people and our catchment area (6 counties) is only a little over 100K. Plasmacytoma incidence in the US is 0.3-0.4/100000. That's 10x the expected rate, just today.
Question regarding cisplatin eligibility:
My understanding is that the usual criteria used for “cisplatin eligibility” with respect to kidney function across the different tumor types such as bladder, lung, h&n, etc. is CrCl >60 mL/min. Borderline eligibility seems to be quoted at usually but not always 50-60 mL/min with sometimes 40-60 mL/min being determined okay for cisplatin use for example when split dosing is used in bladder. The method of choice for calculating CrCl in the clinic seems to be Cockroft-Gault with ideal body weight for normal BMI, adjusted body weight for overweight and above, and actual weight for underweight.
Would love to hear if anyone has any input on how cisplatin eligibility related to kidney function is approached or any other nuances they would share?
My understanding is that the usual criteria used for “cisplatin eligibility” with respect to kidney function across the different tumor types such as bladder, lung, h&n, etc. is CrCl >60 mL/min. Borderline eligibility seems to be quoted at usually but not always 50-60 mL/min with sometimes 40-60 mL/min being determined okay for cisplatin use for example when split dosing is used in bladder. The method of choice for calculating CrCl in the clinic seems to be Cockroft-Gault with ideal body weight for normal BMI, adjusted body weight for overweight and above, and actual weight for underweight.
Would love to hear if anyone has any input on how cisplatin eligibility related to kidney function is approached or any other nuances they would share?
With the data for safety/efficacy of split dose in bladder/urothelial cancer, I've pretty much moved to CrCl 40-60 (however my pharmacist wants to calculate it) gets split dose and everyone else gets full dose, pretty much regardless of the disease state.
Or the air. This is an agricultural area.
I have a meeting with the county health department medical director next week.
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Woah
Well...you're welcome for the head start. And good luck.
On a somewhat random note, I saw 2 new patients yesterday, one with a Grade 1 follicular lymphoma and one with waxing/waning lymphadenopathy and a single FNA showing a low level of monoclonal B cells, both of whom have had B12 levels checked in the last 6 months and both of which were >2x ULN.
Is this something I've been sleeping on for over a decade?
Had a benign heme question.
67 year old. No PMH. Asymptomatic, no infections. One year of worsening neutropenia now ANC 800, fluctuating 800-1.6. WBC 3-4.5. Other counts rock solid, HgB 14, platelets 200.
The WBC and ANC were normal in early 2020s. I was thinking Duffy null associated neutropenia but she was normal in the past.
Copper, folate, B12 normal. Peripheral smear without dysplasia. Hep B/C, HIV negative. No medications that are likely culprits. No rheumatologic symptoms. No autoimmune conditions.
No obvious lymphadenopathy but my lymph node exam isn’t amazing.
The family history of cancer is extremely long including solid and liquid malignant first and second degree regatives.
Any reversible causes I’m missing? I checked all the nutritional labs - copper, B12, folate. I checked drugs. I checked infections.
I’m left with either congenital (unlikely, was normal in early 2020s) versus something in bone marrow, right?
Flow cytometey next?
Thank you
67 year old. No PMH. Asymptomatic, no infections. One year of worsening neutropenia now ANC 800, fluctuating 800-1.6. WBC 3-4.5. Other counts rock solid, HgB 14, platelets 200.
The WBC and ANC were normal in early 2020s. I was thinking Duffy null associated neutropenia but she was normal in the past.
Copper, folate, B12 normal. Peripheral smear without dysplasia. Hep B/C, HIV negative. No medications that are likely culprits. No rheumatologic symptoms. No autoimmune conditions.
No obvious lymphadenopathy but my lymph node exam isn’t amazing.
The family history of cancer is extremely long including solid and liquid malignant first and second degree regatives.
Any reversible causes I’m missing? I checked all the nutritional labs - copper, B12, folate. I checked drugs. I checked infections.
I’m left with either congenital (unlikely, was normal in early 2020s) versus something in bone marrow, right?
Flow cytometey next?
Thank you
I'd throw in a peripheral flow and an SPEP but I'd also just get them set up for a marrow.
LGL? Flow will likely be unhelpful outside of that (and should comment on looking for these guys so pathologists can be aware) bc even if negative you’ll likely need a deeper eval (ie bmbx). Of all the cell lines isolated neutropenia is least likely to be associated with CCUS/mds/aml.
No infections is reassuring. Can also assess for response to gcsf if no etiology uncovered.
Make sure RF and ANA sent even in absence of symptoms
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He has one for every hematological abnormality
60 year old with colon cancer with widespread liver met. Uric acid high at 16, surprisingly with AKI - I’ve never seen high uric acid with colon? But it’s not TLS, other lytes normal. Has only gotten 1 chemo.
How reliable is a G6PD level within 2 weeks of 2 unit blood transfusion? Came back normally 15 (which borderline high).
I want to give rasburicase, but has ethnic background with high risk of deficiency. The test came back normal at the high end but I’m wondering the PRBCs gave me a falsely normal result.
I could sequence it but that takes 2-3 weeks.
How reliable is a G6PD level within 2 weeks of 2 unit blood transfusion? Came back normally 15 (which borderline high).
I want to give rasburicase, but has ethnic background with high risk of deficiency. The test came back normal at the high end but I’m wondering the PRBCs gave me a falsely normal result.
I could sequence it but that takes 2-3 weeks.
Maybe different because your patient is 60 so you probably have more data points, but I did have a few cases where a 30-40 year old was sent to me for "new neutropenia" but then looking back at the 2-3 old "normal" labs, they were all drawn when they were sick or in the ER, etc
Yeah, I see this all the time. If there's one thing that PCPs around here are good at, it's post-hospital f/u. So someone gets hospitalized for whatever (sepsis, GI bleed, etc), sees PCP a day or two after discharge, they look at labs during hospitalization, see high or low whatevers on the CBC and decide they have acute leukemia and need a STAT heme consult.
Question, are you guys doing DPD testing prior to 5FU, and if so how do you approach in situations where pt has rapid / late presenting disease where you can't wait the couple of weeks for PGX to come back. I hear Guardant liquid is now including DPD testing but not sure how good the report is in telling you how to dose reduce.
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Not really. I just did one the other day for no particular reason other than young and anxious. It was negative and came back in a week. I can't get prior auth for chemo that fast anyway so it's not like it delayed treatment.
My prior institution made it mandatory after a lawsuit that I was named in and then dropped from. The plaintiff eventually settled for $1 and this requirement, as well as mandatory "fluoropyrimidine toxicity education" for everyone in the division.
It's SOC in Europe, but not in the US.
My own personal experience over almost 15 years as an attending is that less than half of the people with significant fluoropyrimidine toxicity have a DPD deficiency. And even if they do, it's easily recognized and managed in the same way you'd do it if you knew about it ahead of time...stop the drug, let the toxicity resolve, restart at 50%.
Tempus has started reflexing DPD/UGT1A1 for all colon cancers… of course it often isn’t back until Cycle #2.
These tests seem more useful for lawyers than physicians tbh. I feel like waiting to get DPD on every single 5FU patient would probably harm more patients than it helps (although the number of each would be extremely small).
These tests seem more useful for lawyers than physicians tbh. I feel like waiting to get DPD on every single 5FU patient would probably harm more patients than it helps (although the number of each would be extremely small).
65 year old woman. HgB 10. MCV 90. Ferritin 900, %sat 44. Retic count inappropriately normal at 1.6%. HFE gene testing negative. Remainder of CBC normal - WBC 6, diff normal, platelets 250. Nothing on smear except anemia. Copper, B12, folate, normal. Liver, kidneys normal. No hemolysis. No family history of blood/iron disorders. No obvious source of inflammation/autoimmune conditions.
I am planning on a bone marrow and liver MRI.
I haven’t run across the combination of iron overload and anemia like this - is this a common presentation for patients who have many years of ineffective erythropoiesis?
MDS patients get iron overload from their transfusions of course, I just wasn’t aware it could happen before (assuming this is MDS).
I am planning on a bone marrow and liver MRI.
I haven’t run across the combination of iron overload and anemia like this - is this a common presentation for patients who have many years of ineffective erythropoiesis?
MDS patients get iron overload from their transfusions of course, I just wasn’t aware it could happen before (assuming this is MDS).
I actually have 2 of these that I'm in the middle of working up ATM. Planning for marrows as well. I haven't seen this combination before either so not helpful to you at all.
Another bizarre coincidence - I was just asked if I should see a patient with ESRD, normal calcium and mildly elevated PTHrP (sent in the setting of calcium that was high once a few months ago, although subsequently the calcium normalized and ionized calcium is also normal) without any evidence of malignancy clinically.
Anyway, I looked into it and most labs doing PTHrP tests will use a C-terminal assay which can be elevated in pts with CKD; an N-terminal assay will apparently be normal (citation).
Whether I'll be able to actually find a lab that can run this test is another question, but at least I feel like in my patient's case, the ESRD is a decent enough explanation.
Very interesting and I do think maybe that helps me but I forget all the details, good find! I can barely get our local lab group to add PIK3CA for colon patients so I can’t imagine I’ll have any luck with that specific test but who knows…
Separate generalized question for the group: any tips or general thought process behind teasing out whether someone has true progression vs pseudoprogression when started on Immunotherapy? I’m thinking for dMMR CRC, Melanoma or maybe RCC on Nivo/Ipi. It feels like the general consensus is 🤷🏼♂️🤷🏼♂️🤷🏼♂️
It makes me feel strangely better knowing I’m not just being obtuse and missing an obvious answer. I’ll update the group with the marrow!
Another case:
Stage III upper tract urothelial. Post-surgery imaging negative. Patient didn’t get neoadjuvant because urology didn’t have them see med onc before nephrectomy and now GFR is 30.
I am sending ctDNA but will take a few weeks.
I want to just give enfortumab and pembro as an adjuvant regimen. It’s been studied in EV-303 and has superior DFS/OS in cisplatin ineligible MIBC patients (only data I see is from Pfizer so far, no publications yet - PADCEV™ Plus KEYTRUDA™ Significantly Improves Survival for Certain Patients with Bladder Cancer When Given Before and After Surgery | Pfizer).
My only guideline approved option is single agent IO which feels inadequate for a healthy 58 year old.
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I'd expect a higher Tsat for true iron overload, though you're not wrong to get a liver MRI anyway
I've seen some low grade lymphomas involving only the bone marrow and patients are otherwise asymptomatic
I'm also seeing two patients in follow-up tomorrow that are similar:
One diagnosed initially with a very high ferritin and unexplained anemia with nothing else on the work-up (similar to yours) that ended up having non-secretory myeloma (though had a high MCV on initial presentation)
The other was a very healthy ~80 year old with mild normocytic anemia (Hgb was like 12, but downtrending from prior) and nothing else going on where I initially thought the PCP was being overly cautious in sending the referral, but I sent work-up including SPEP, FLC, etc and ended up having myeloma with >80% BM involvement
So yes, definitely let us know what the marrow shows =)
How long have they been on it? If it's first interim restaging and clinically fine, I'd keep going. Also, what imaging modality? If CT, I'd try a PET if there was a prior for comparison.
I don't think I'd be super excited about anything at this point unless the ctDNA was positive. Enfortumab/Pembro is a reasonable approach but unclear what the benefit would be in UTUC.
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Usually I'm dealing with it in the context of restaging after the 4th cycle of Nivo/Ipi prior to going to Nivo monotherapy.
I'll have to check on the PET idea, that's a good thought... although would we expect pseudoprogression to possibly show increased PET avidity as well? I suppose if that was a reliable way of evaluating it, I would probably start ordering PETs more often when patients have an indication for dual IO
It also depends on what you mean by progression. Slight interval enlargement of known disease? Reasonable to continue to single agent and watch closely. Development of new disease? Nope. Time for a new plan.
EV-P sounds reasonable if you have access in this setting and tou feel comfortable with the press release without a more granular dissection of the data. My hypothesis is that the benefit will be drawn from the neoaduvant pCR patients. Adjuvant nivo is the most evidence based treatment.
For some of my rcc patients, if they are clinically well (or better yet, improved from pre ICI ECOG), I tend to restage in 6 weeks
Appreciate the thoughts from you and @GUoncologist .
Interestingly when you read about the data that came out of melanoma the pseudoprogression phenomenon also included patients who developed new lesions that later regressed. I guess it’s just an area with no easy answers, particularly frustrating given the stakes involved with abandoning a treatment line. I’ll see how they’re doing clinically I suppose
Have a cT2 or cT3 (maybe some prostate extension) bladder cancer with squamous differentiation, at least 50% per pathology.
Would anyone do anything different than just neoadjuvant gem/cis/durva?
Both gem/cis/durva and pembro-EV trials enrolled squamous differentiated bladder cancers. Technically the correct NCCN answer is gem/cis/durva perioperative therapy but squamous bladder is a tricky one.
Would anyone do anything different than just neoadjuvant gem/cis/durva?
Both gem/cis/durva and pembro-EV trials enrolled squamous differentiated bladder cancers. Technically the correct NCCN answer is gem/cis/durva perioperative therapy but squamous bladder is a tricky one.
I’d probably go with Gem/Cis/Durva.
Pt w/ multiply recurrent oral cavity SCC treated with surgery + adjuvant CRT then salvage surgery for local recurrence then had distant mets treated with pembro and maintained CR for 5 years. Subsequently, after pembro was discontinued out of caution (although well tolerated), he has had a local recurrence treated with salvage surgery, and now has another local recurrence a couple years later. He will undergo surgery, but the question is whether maintenance pembro should be resumed post-op given all of these recurrences and since he had good control before. The downsides would be it's unclear how much benefit he would derive and there would be no index lesion to follow on scans. The alternative would just be observation.
This definitely doesn't fall under the category of "adjuvant" treatment. If he's rendered NED by surgery, I'd just watch closely. You'll get the chance to try IO at recurrence, maybe even before surgery (if an option) in order to help you determine response.
I saw this exact consult last week! I emailed our local area’s lab to ask about the assay… we’ll see if I ever hear back.
Much props to you, even remembering your article in the thread I did not come across it on Pubmed and ended up having to dig it out of this thread lol
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If I ever get this consult, I'm just going to say "it's ESRD" and call it a day.
Had two benign heme questions.
1. 51 year old woman with history 1 provoked and 1 unprovoked thrombosis as well as miscarriages x 2. Anticardiolipin and glycoprotein strongly positive (> 700, > 130) on 1 check pending repeat 12 weeks apart for confirmation. Daughter is considering starting OCPs --would you recommend she get tested for APLS first?
2. 88 year old with 10 year history of thrombocytopenia without any other CBC abnormalities except monocytosis (~4000). Platelets 20-30. Had zero response to dex 40 mg * 4 days. I am assuming this is chronic ITP refractory to steroids, and I am not going crazy with a marrow or imaging (monocytosis can be reactive to thrombocytopenia, so that's my explanation for that). Patient has a history of stroke (not on AC due to low platelets of course) as well as falls without headstrike, and I am considering a TPO-RA agonist, which has a thrombotic risk. Would anyone be hesitant to start TPO-RA in a stroke patient? I could just let him live his life in the 20-30K range and tell him to be careful not to fall?
1. 51 year old woman with history 1 provoked and 1 unprovoked thrombosis as well as miscarriages x 2. Anticardiolipin and glycoprotein strongly positive (> 700, > 130) on 1 check pending repeat 12 weeks apart for confirmation. Daughter is considering starting OCPs --would you recommend she get tested for APLS first?
2. 88 year old with 10 year history of thrombocytopenia without any other CBC abnormalities except monocytosis (~4000). Platelets 20-30. Had zero response to dex 40 mg * 4 days. I am assuming this is chronic ITP refractory to steroids, and I am not going crazy with a marrow or imaging (monocytosis can be reactive to thrombocytopenia, so that's my explanation for that). Patient has a history of stroke (not on AC due to low platelets of course) as well as falls without headstrike, and I am considering a TPO-RA agonist, which has a thrombotic risk. Would anyone be hesitant to start TPO-RA in a stroke patient? I could just let him live his life in the 20-30K range and tell him to be careful not to fall?
I would recommend it.
Rituximab? IVIG? Rilzabrutinib?
I'd try rituximab first personally. I haven't tried rilzabrutinib yet but it seems to be similar in efficacy to TPO-RA with a better safety profile.
Letting him ride it out as long as his platelets are >20K also isn't the wrong answer, but I do get anxious in older people who have a tendency to "fall down, go boom".
Agree with GutOnc I tend to always recommend they discuss it with their OB with any history of VTE in family or not. I’m not a fan of OCPs and feel like alternatives (IUD) should almost always be considered.
This case is often in the back of my mind when OCPs come up.
I would personally strongly consider a marrow in a patient that had zero response to steroids. I would also lean toward Rituximab as well even if the thrombotic risk is just theoretical/low.
In a 68yo I would. But in an 88yo? I'd probably just try to ride it out for as long as I could.
Don't ask questions you don't want to know the answer to.
I hear you, but if you’re talking about giving Rituximab/Promacta I think it’d be worth looking into why the platelets are actually low first.
I would not be saying this if the patient responded to steroids initially but then relapsed after a few weeks, but if the patient truly had NO response to steroids that is pretty unusual for ITP and I’d argue them being 88 instead of 68 is even more reason to question the diagnosis of ITP.
Thrombocytopenia with no response to steroids/IVIG with monocytosis could easily be CMML, though your point about a reactive monocytosis is reasonable. What has the tenor of both been, stable in the range you noted? Trying tpo agonist isn’t crazy but probably would recommend marrow first since any risk associated with it wouldn’t be the same risk/benefit if you’re not using the correct treatment for the underlying disease…
Did the PLT counts progressively get worse, or bounce around a lot? I would probably also favor doing a bone marrow before starting a TPO-RA. Could be CMML.
If you haven't done IVIG yet, it can be a nice diagnostic and therapeutic maneuver because you really should question the ITP dx in a patient who doesn't respond to IVIG (even moreso than the lack of steroid response).
I'd have more optimism about rituximab if he had a response to IVIG
Thank you all - this is hugely, hugely helpful.
For this the 88 year old with absolutely zero response to dex 40, the thrombocytopenia has been present for a decade with a progressive march down from 150 to 30 in a pretty straight line without any other CBC abnormalities. Not much bouncing around. Also the monocytosis started at the exact time the platelets dropped below 150 and has been steadily marching up as platelets have dropped.
I’ll send flow to just see if there’s any evidence of CMML. The smear just showed a ton of monocytes. And I’ll maybe send anti platelet antibody testing - I was always taught that you’re never really supposed to send this, but if it’s positive, might make me more confident it’s ITP.
In terms of diagnostics, I like the idea of trying IVIG or Rituximab as both a therapeutic and diagnostic maneuver.
I was worried about the immunosuppressive effect in an 88 year old with Rituxumab, but I think I was probably just psyching myself out. Probably makes more sense than TPO-RA due to his stroke history.
Really appreciate it all.
For this the 88 year old with absolutely zero response to dex 40, the thrombocytopenia has been present for a decade with a progressive march down from 150 to 30 in a pretty straight line without any other CBC abnormalities. Not much bouncing around. Also the monocytosis started at the exact time the platelets dropped below 150 and has been steadily marching up as platelets have dropped.
I’ll send flow to just see if there’s any evidence of CMML. The smear just showed a ton of monocytes. And I’ll maybe send anti platelet antibody testing - I was always taught that you’re never really supposed to send this, but if it’s positive, might make me more confident it’s ITP.
In terms of diagnostics, I like the idea of trying IVIG or Rituximab as both a therapeutic and diagnostic maneuver.
I was worried about the immunosuppressive effect in an 88 year old with Rituxumab, but I think I was probably just psyching myself out. Probably makes more sense than TPO-RA due to his stroke history.
Really appreciate it all.
Regarding locally advanced esophageal SCC patients treated with definitive chemoradiation without any plans for subsequent surgery, is there a role for adjuvant/consolidative immunotherapy a la PACIFIC? Or is "adjuvant" immunotherapy restricted to CheckMate 577 where patients have R0 resection after neoadjuvant CRT?
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