clinical cases

[randomhemoncpd]

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I've got a guy with myelofibrosis on ruxolitinib. He's had a very robust clinical response to treatment (his spleen was touching his pubic ramus, he'd lost 30# and could barely get off the couch) but he's also struggled with persistent symptomatic anemia.

When I first started him on treatment, he developed a Coombs positive hemolytic anemia. I stopped rux, treated it with steroids, it got better and now I'm titrating up his rux again. He's now (6 months later) developing worsening anemia. Not nearly as bad as prior but worrisome. I got another set of hemolysis labs to try and figure out if the anemia is hemolysis, MF or rux. His Coombs is negative and his bili is normal but his haptoglobin is undetectable again. I'm not sure how to interpret this and if I should be treating this as hemolysis again.

Spleen get bigger at all? Either way might be worth trying momelotinib

 

[whoknows2012]

Spleen get bigger at all? Either way might be worth trying momelotinib

I second momelotinib especially if anemia is not hemolysis. Still has jak1/jak2 inhibition though probably not as good an anti inflammatory drug as rux. Some data supporting improved long term outcomes as well…

 

[gutonc]

Spleen get bigger at all? Either way might be worth trying momelotinib

No, spleen's back where it belongs. Overall doing better.

I'll see how things shake out over the next few weeks and consider momelotinib.

 

[lifeofpi1]

Wanted to get everyone's thoughts on their thoughts on this case:

65M fit patient with metastatic GEJ adeno with pMMR/MSS, CPS 15, HER2 neg, CLDN 18.1/2 neg but w/ baseline neuropathy precluding platinum.

Let's say no trial options. I am considering FOLFIRI as 1L Tx, but should aPD-1 be added?

There is no data for this at least in the 1L setting, but PRODIGE 59-FFCD 1707-DURIGAST looked at FOLFIRI + Durva +/- Treme in 2L and was a negative study. However, no surprises in terms of toxicity and, as expected, an additional ~10% of patients have durable disease control probably owing to IO.

1. Is adding aPD-1 to FOLFIRI reasonable given that we know it has OS benefit when added to platinum-based Tx?
2. Would anyone consider another approach other than FOLFIRI +/- IO?

 

[osprey099]

Wanted to get everyone's thoughts on their thoughts on this case:

65M fit patient with metastatic GEJ adeno with pMMR/MSS, CPS 15, HER2 neg, CLDN 18.1/2 neg but w/ baseline neuropathy precluding platinum.

Let's say no trial options. I am considering FOLFIRI as 1L Tx, but should aPD-1 be added?

There is no data for this at least in the 1L setting, but PRODIGE 59-FFCD 1707-DURIGAST looked at FOLFIRI + Durva +/- Treme in 2L and was a negative study. However, no surprises in terms of toxicity and, as expected, an additional ~10% of patients have durable disease control probably owing to IO.

1. Is adding aPD-1 to FOLFIRI reasonable given that we know it has OS benefit when added to platinum-based Tx?
2. Would anyone consider another approach other than FOLFIRI +/- IO?

Any peritoneal disease? Can consider tislelizumab per RATIONALE-305. They just used "chemo" + tislelizumab. Benefit was most seen in the subset of folks who had peritoneal disease

 

[lifeofpi1]

Any peritoneal disease? Can consider tislelizumab per RATIONALE-305. They just used "chemo" + tislelizumab. Benefit was most seen in the subset of folks who had peritoneal disease

Thanks! It seems though the investigators choice chemo backbone for RATIONALE-305 were FOLFOX/CAPOX/5FU+cis. Still, interesting to know most benefit in those w/ peritoneal ds.

 

[Adjet]

Wanted to get everyone's thoughts on their thoughts on this case:

65M fit patient with metastatic GEJ adeno with pMMR/MSS, CPS 15, HER2 neg, CLDN 18.1/2 neg but w/ baseline neuropathy precluding platinum.

Let's say no trial options. I am considering FOLFIRI as 1L Tx, but should aPD-1 be added?

There is no data for this at least in the 1L setting, but PRODIGE 59-FFCD 1707-DURIGAST looked at FOLFIRI + Durva +/- Treme in 2L and was a negative study. However, no surprises in terms of toxicity and, as expected, an additional ~10% of patients have durable disease control probably owing to IO.

1. Is adding aPD-1 to FOLFIRI reasonable given that we know it has OS benefit when added to platinum-based Tx?
2. Would anyone consider another approach other than FOLFIRI +/- IO?

With a CPS >10, I would definitely be in favor of adding IO regardless of the chemo choice. FOLFIRI seems reasonable if you think platinum is absolutely contraindicated. Other option if you think it's more of a relative contraindication would be to start with FOLFOX, closely monitor neuropathy and d/c oxaliplatin or switch to irinotecan at first sign of QoL deterioration from neuropathy.

 

[gutonc]

With a CPS >10, I would definitely be in favor of adding IO regardless of the chemo choice. FOLFIRI seems reasonable if you think platinum is absolutely contraindicated. Other option if you think it's more of a relative contraindication would be to start with FOLFOX, closely monitor neuropathy and d/c oxaliplatin or switch to irinotecan at first sign of QoL deterioration from neuropathy.

Agreed. I'd definitely use some sort of IO. I don't think there's a magic recipe for this though. You could do pembro, or ipi/nivo, or nivo, or durva, or durva/trem. I'd also probably try to use a platinum first line and monitor closely. In pre-existing peripheral neuropathy for a fit patient (ECOG 0-1), I might try cisplatin since it has less peripheral neuropathy than oxali (more other toxicity though) and is likely a little more effective. But you wouldn't be wrong to try oxali. And if the patient was adamant about not doing anything that might worsen the neuropathy, then FOLFIRI is totally reasonable.

 

[lifeofpi1]

With a CPS >10, I would definitely be in favor of adding IO regardless of the chemo choice. FOLFIRI seems reasonable if you think platinum is absolutely contraindicated. Other option if you think it's more of a relative contraindication would be to start with FOLFOX, closely monitor neuropathy and d/c oxaliplatin or switch to irinotecan at first sign of QoL deterioration from neuropathy.

Agreed. I'd definitely use some sort of IO. I don't think there's a magic recipe for this though. You could do pembro, or ipi/nivo, or nivo, or durva, or durva/trem. I'd also probably try to use a platinum first line and monitor closely. In pre-existing peripheral neuropathy for a fit patient (ECOG 0-1), I might try cisplatin since it has less peripheral neuropathy than oxali (more other toxicity though) and is likely a little more effective. But you wouldn't be wrong to try oxali. And if the patient was adamant about not doing anything that might worsen the neuropathy, then FOLFIRI is totally reasonable.

Thank you both.

I actually think neuropathy is more a relative contraindication. Will consider FOLFOX + IO with close monitoring and Irinotecan switch at first sign of QoL deterioration.

 

[bobsmith]

Any peritoneal disease? Can consider tislelizumab per RATIONALE-305. They just used "chemo" + tislelizumab. Benefit was most seen in the subset of folks who had peritoneal disease

I hadn't heard of this

I looked up the subgroup analysis from the RATIONALE 305 paper:

Seems like pretty similar benefit regardless of peritoneal mets?

 

[osprey099]

I hadn't heard of this

I looked up the subgroup analysis from the RATIONALE 305 paper:View attachment 400987
Seems like pretty similar benefit regardless of peritoneal mets?

I think it was more that this trial included those with peritoneal disease whereas others (nivo/pembro) didn't or didn't show the benefit in peritoneal disease.

 

[guildsman]

Wanted to get everyone's thoughts on their thoughts on this case:

65M fit patient with metastatic GEJ adeno with pMMR/MSS, CPS 15, HER2 neg, CLDN 18.1/2 neg but w/ baseline neuropathy precluding platinum.

Let's say no trial options. I am considering FOLFIRI as 1L Tx, but should aPD-1 be added?

There is no data for this at least in the 1L setting, but PRODIGE 59-FFCD 1707-DURIGAST looked at FOLFIRI + Durva +/- Treme in 2L and was a negative study. However, no surprises in terms of toxicity and, as expected, an additional ~10% of patients have durable disease control probably owing to IO.

1. Is adding aPD-1 to FOLFIRI reasonable given that we know it has OS benefit when added to platinum-based Tx?
2. Would anyone consider another approach other than FOLFIRI +/- IO?

Depending on how severe the neuropathy is, I routinely use FOLFOX with cryotherapy in patients with neuropathy and have been able to get most patients through at least 6 cycles. My recommendation is FOLFOX + Nivolumab first line or if severe neuropathy then FOLFIRI + Nivolumab. There is, however, no high quality data for FOLFIRI + IO in the first line.

Think about your sequence choices (there is also a second line SWOG trial of adding immunotherapy to Taxol/Ram):

1. FOLFOX + Nivo --> Taxol/Ram OR FOLFIRI +/- Ram --> Taxol/Ram OR FOLFIRI +/- Ram --> Lonsurf
2. FOLFIRI + Nivo --> Taxol/Ram -->Lonsurf (Edit, Wrote FOLFIRI in sequence twice)

Either way you will have to expose the patient to a neuropathy causing agent in the first or second line. Your biggest benefit will be when the cancer is most sensitive and the patient is most fit.

 

[lifeofpi1]

Depending on how severe the neuropathy is, I routinely use FOLFOX with cryotherapy in patients with neuropathy and have been able to get most patients through at least 6 cycles. My recommendation is FOLFOX + Nivolumab first line or if severe neuropathy then FOLFIRI + Nivolumab. There is, however, no high quality data for FOLFIRI + IO in the first line.

Think about your sequence choices (there is also a second line SWOG trial of adding immunotherapy to Taxol/Ram):

1. FOLFOX + Nivo --> Taxol/Ram OR FOLFIRI +/- Ram --> Taxol/Ram OR FOLFIRI +/- Ram --> Lonsurf
2. FOLFIRI + Nivo --> Taxol/Ram --> FOLFIRI -->Lonsurf

Either way you will have to expose the patient to a neuropathy causing agent in the first or second line. Your biggest benefit will be when the cancer is most sensitive and the patient is most fit.

Thanks. It seems the consensus is to try as much as possible to use FOLFOX + IO but FOLFIRI + IO is a reasonable alternative, especially with higher CPS.

 

[osprey099]

Staying on the topic of GI... I have a 82M (ecog 1) with metastatic GEJ adenocarcinoma with peritoneal mets. Minimally symptomatic right now fortunately. His molecular profile is quite interesting: HER2(2+, FISH positive), Claudin18.2 positive, PD-L1 CPS 10%.

What would you do amongst the following options?

1) FOLFOX/zolbetuximab
2) FOLFOX/trastuzumab/pembro
3) FOLFOX/trastuzumab (cause he's old and option 2 is quite hard to handle)
4) FOLFOX/tislelizumab (cause this is only IO shown effective in peritoneal mets)

I am leaning towards going after the Claudin18.2 (option 1) first, and then doing Tdxd on relapse. Any other thoughts?

 

[gutonc]

Staying on the topic of GI... I have a 82M (ecog 1) with metastatic GEJ adenocarcinoma with peritoneal mets. Minimally symptomatic right now fortunately. His molecular profile is quite interesting: HER2(2+, FISH positive), Claudin18.2 positive, PD-L1 CPS 10%.

What would you do amongst the following options?

1) FOLFOX/zolbetuximab
2) FOLFOX/trastuzumab/pembro
3) FOLFOX/trastuzumab (cause he's old and option 2 is quite hard to handle)
4) FOLFOX/tislelizumab (cause this is only IO shown effective in peritoneal mets)

I am leaning towards going after the Claudin18.2 (option 1) first, and then doing Tdxd on relapse. Any other thoughts?

I'd probably do FOLFOX+Tras first followed by zolbetuximab based in 2nd line. Is zolbetuximab approved in 1st line yet?

I'll be honest and say that I've never had the opportunity to give zolbetuximab yet so can't comment on it's tolerability, but I think FOLFOX+Tras is pretty well tolerated and if tolerance becomes the issue (rather than progression), you could easily switch to T-DXd.

 

[osprey099]

I'd probably do FOLFOX+Tras first followed by zolbetuximab based in 2nd line. Is zolbetuximab approved in 1st line yet?

I'll be honest and say that I've never had the opportunity to give zolbetuximab yet so can't comment on it's tolerability, but I think FOLFOX+Tras is pretty well tolerated and if tolerance becomes the issue (rather than progression), you could easily switch to T-DXd.

I don't think zolb is approved in 2L so my only opportunity to use it is 1L, but it is very very nauseating.

My reason for favoring zolb in 1L is cause I can always do HER2 therapy in 2L, but not vice versa.

If you went 1L HER2, would you add the pembro with the tras?

 

[ONC2023]

SPOTLIGHT and GLOW both excluded HER2+ patients, so I think in the setting of HER2 positivity, zolbetuximab therapy isn’t approved in any setting.

Edit: yes according to FDA label, it seems restricted to Her2 negative patients: “VYLOY is a claudin 18.2-directed cytolytic antibody and is indicated in combination with fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of adults with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive as determined by an FDA-approved test.”

 

[Adjet]

I don't think zolb is approved in 2L so my only opportunity to use it is 1L, but it is very very nauseating.

My reason for favoring zolb in 1L is cause I can always do HER2 therapy in 2L, but not vice versa.

If you went 1L HER2, would you add the pembro with the tras?

I probably would offer to add the pembro to trastuzumab. Doesn't add too much toxicity such that I think potential benefits make it worthwhile.

 

[guildsman]

Staying on the topic of GI... I have a 82M (ecog 1) with metastatic GEJ adenocarcinoma with peritoneal mets. Minimally symptomatic right now fortunately. His molecular profile is quite interesting: HER2(2+, FISH positive), Claudin18.2 positive, PD-L1 CPS 10%.

What would you do amongst the following options?

1) FOLFOX/zolbetuximab
2) FOLFOX/trastuzumab/pembro
3) FOLFOX/trastuzumab (cause he's old and option 2 is quite hard to handle)
4) FOLFOX/tislelizumab (cause this is only IO shown effective in peritoneal mets)

I am leaning towards going after the Claudin18.2 (option 1) first, and then doing Tdxd on relapse. Any other thoughts?

in a very fit 82 year old FOLFOX + Trastuzumab + Pembrolizumab. CLDN is not studied in HER2 amplified tumors, it is also incredibly emetogenic (people vomit in the middle of the infusion with 4+ anti-emetic premeds).

 

[lifeofpi1]

Another case of concern for neuropathy affecting regimen choice.

76M ECOG 1-2 with metastatic PD-L1 TPS 45% and driver mutation-neg lung SQCC with a symptomatic mediastinal tumor causing some mass effect. Has a history of bad trigeminal neuralgia which is now better controlled on prophylactic med.

Given the preference for a brisk response, I would like to choose a chemoIO regimen. However, in addition to the pt being worried about the theoretical possibility of exacerbating the now-better controlled TN, the current prophylactic med has P450 interaction w/ Taxol which would require a large upfront dose-increase of Taxol (50%), if it were to be used.

So, what would you choose among these options?

1) Durva/Tremi/Carbo/Gem (concern for tolerability w/ 4 drug regimen?)
2) Nivo/Ipi (response may not be brisk enough?)
3) Sintilimab/Carbo/Gem (ORIENT-12 not part of guideline but carbo/gem an effective backbone in SCC)

I'm considering going with Carbo/Gem + anti-PD-1.

 

[osprey099]

Another case of concern for neuropathy affecting regimen choice.

76M ECOG 1-2 with metastatic PD-L1 TPS 45% and driver mutation-neg lung SQCC with a symptomatic mediastinal tumor causing some mass effect. Has a history of bad trigeminal neuralgia which is now better controlled on prophylactic med.

Given the preference for a brisk response, I would like to choose a chemoIO regimen. However, in addition to the pt being worried about the theoretical possibility of exacerbating the now-better controlled TN, the current prophylactic med has P450 interaction w/ Taxol which would require a large upfront dose-increase of Taxol (50%), if it were to be used.

So, what would you choose among these options?

1) Durva/Tremi/Carbo/Gem (concern for tolerability w/ 4 drug regimen?)
2) Nivo/Ipi (response may not be brisk enough?)
3) Sintilimab/Carbo/Gem (ORIENT-12 not part of guideline but carbo/gem an effective backbone in SCC)

I'm considering going with Carbo/Gem + anti-PD-1.

Metastatic lung cancer >>>> Trigeminal neuralgia. Stop then TN drug, give carbo/pac/pembro for a few cycles and transition to pembro maintenance. Can restart the TN drug when going to just pembro maintenance. He won't have control of TN for a few months but at least he'll be alive

 

[gutonc]

Metastatic lung cancer >>>> Trigeminal neuralgia. Stop then TN drug, give carbo/pac/pembro for a few cycles and transition to pembro maintenance. Can restart the TN drug when going to just pembro maintenance. He won't have control of TN for a few months but at least he'll be alive

I'm going to disagree with you on this. He's got metastatic disease. This isn't getting cured. QOL is going to be paramount and if his TN is severe enough, he may stop altogether before getting sufficient disease response.

I also think that if local disease is the biggest problem ATM, treat the local disease and then go systemic. You're not going to get a super rapid response from any systemic therapy no matter how many drugs you give. So get rad onc off the golf course and do some palliative XRT. Maybe it's too big or too close to the esophagus for SBRT, but you can always do a hypofractionated course of palliative radiation and then follow that up with systemic therapy, I'd probably use dual IO.

If rad onc won't sack up, then just give carbo/taxol/pembro at standard taxol dosing and recognize that you're going to be functionally dose reducing it by 40% or so and just live with that, maybe titrate up as tolerated. Carbo/Gem/IO of some sort isn't a terrible idea either.

This is one of those situations where you can't really make a wrong choice, and you can always change things up if you need to.

 

[evilbooyaa]

I'm going to disagree with you on this. He's got metastatic disease. This isn't getting cured. QOL is going to be paramount and if his TN is severe enough, he may stop altogether before getting sufficient disease response.

I also think that if local disease is the biggest problem ATM, treat the local disease and then go systemic. You're not going to get a super rapid response from any systemic therapy no matter how many drugs you give. So get rad onc off the golf course and do some palliative XRT. Maybe it's too big or too close to the esophagus for SBRT, but you can always do a hypofractionated course of palliative radiation and then follow that up with systemic therapy, I'd probably use dual IO.

If rad onc won't sack up, then just give carbo/taxol/pembro at standard taxol dosing and recognize that you're going to be functionally dose reducing it by 40% or so and just live with that, maybe titrate up as tolerated. Carbo/Gem/IO of some sort isn't a terrible idea either.

This is one of those situations where you can't really make a wrong choice, and you can always change things up if you need to.

As a Rad Onc lurking this thread, my thought immediately went to "why not use the things that gives response the fastest - palliative RT"

Mediastinal mass causing mass effect is a precursor to SVC syndrome which is a Rad Onc emergency. Most Rad Oncs would love to help out with the patient as they are now, not when they're actively dying in the hospital from their SVC syndrome.

 

[gutonc]

As a Rad Onc lurking this thread, my thought immediately went to "why not use the things that gives response the fastest - palliative RT"

Mediastinal mass causing mass effect is a precursor to SVC syndrome which is a Rad Onc emergency. Most Rad Oncs would love to help out with the patient as they are now, not when they're actively dying in the hospital from their SVC syndrome.

I was being a little sarcastic in my wording, but my point was that this case is not just a medical oncology issue. Nothing that we have in our armamentarium is going to get this patient a rapid enough response for it to be meaningful. It’s time to aim the healing photons.

 

[Plutarch02]

https://ascopubs.org/doi/10.1200/JCO.22.01503

Ipi nivo outperforms chemo in stage IV NSCLC, generally you only do chemo the first two cycles of it though to address the time to response issue.

 

[ONC2023]

Have a simple perioperative anticoagulation question.

Have a 50 year old with left leg DVT, likely unprovoked, now on DOAC for 4 weeks. He has localized prostate cancer and has decided for radical prostatectomy.

My question: can you take him to surgery at any time with perioperative lovenox bridge, or is it better to do 3 months (6 months?) of anticoagulation before taking someone to a non-emergent surgery when they have an acute DVT?

For a non-emergent surgery, I would likely favor doing 3 months of anticoagulation at least and then do a lovenox bridge perioperatively - but I actually have not managed AC in a situation where someone needed non-emergent surgery in the setting of an acute DVT.

 

[HemeOncHopeful19]

No reason to bridge with a DOAC

I tend to wait minimum 1 up to 3 months depending on the urgency of the surgery... prostate cancer is probably a borderline case, for example are they going to be on ADT during this time? When will surgery actually happen - will it be 8-10 weeks by that point?

If needing urgent surgery and can't anticoagulant for a minimum of 1 month I tend to recommend IVC filter (CYA).
You could also argue DVT provoked by malignancy IMO

 

[gutonc]

I have yet to meet a surgeon who will take anyone to the OR for a non-emergent case within 3 months of an acute VTE.

This isn’t even an urgent surgery. Give a hit of Lupron and go to the OR in 3 months.

 

[HemeOncHopeful19]

Anyone have any thoughts on (curative intent) GEJ/Gastric cancer in patients with baseline neuropathy?

I’m surprised I haven’t encountered this scenario before but I’m struggling with how to approach it. I guess ECF might have less neuropathy than FLOT but that has its own trade offs and there doesn’t seem to be any good regimen that really manages to avoid it…

 

[gutonc]

Anyone have any thoughts on (curative intent) GEJ/Gastric cancer in patients with baseline neuropathy?

I’m surprised I haven’t encountered this scenario before but I’m struggling with how to approach it. I guess ECF might have less neuropathy than FLOT but that has its own trade offs and there doesn’t seem to be any good regimen that really manages to avoid it…

I just cross my fingers and hope for the best (assuming the patient is in agreement). Agree that ECF is an option but not a great one.

 

[gutonc]

Not an actual clinical case, but I have a referral on my schedule today for "acquired alpha thalassemia".

It's actually Hb Lepore, which she was diagnosed with 25 years ago. Her labs are completely unchanged since 1999 (first ones in her chart).

Jenny McJennerson at her best here.

 

[HemeOncHopeful19]

This feels like a dumb/basic question, but I’m curious what people consider to qualify as “clinical obstruction” as far as a high risk factor for Stage 2 colon cancer.

Clearly if patient is admitted for obstruction requiring urgent surgery it’s a no-brainer. But what about those asymptomatic but “partially obstructing” on colonoscopy masses, or even a mass that causes obstruction to where they can’t pass the scope but patient was otherwise asymptomatic?

 

[gutonc]

This feels like a dumb/basic question, but I’m curious what people consider to qualify as “clinical obstruction” as far as a high risk factor for Stage 2 colon cancer.

Clearly if patient is admitted for obstruction requiring urgent surgery it’s a no-brainer. But what about those asymptomatic but “partially obstructing” on colonoscopy masses, or even a mass that causes obstruction to where they can’t pass the scope but patient was otherwise asymptomatic?

If they're pooping, they're not obstructed. At least, that's what my colorectal surgery colleagues tell me.

 

[MOFellow_9]

Is there a context where you guys would offer chemoradiotherapy to someone with locally advanced pancreatic cancer?

Recently admitted a pancreatic cancer patient due to cholangitis and saw his treating physician was about to start chemoradiotherapy for local control after local progression to 10 cycles of mFOLFIRINOX. I feel I've seen chemoradiotherapy in this context only a handful of times, most of the times after progression to mFOLFIRINOX I've seen attendings prefer a 2L systemic approach. Can give more details if useful

 

[gutonc]

Is there a context where you guys would offer chemoradiotherapy to someone with locally advanced pancreatic cancer?

Recently admitted a pancreatic cancer patient due to cholangitis and saw his treating physician was about to start chemoradiotherapy for local control after local progression to 10 cycles of mFOLFIRINOX. I feel I've seen chemoradiotherapy in this context only a handful of times, most of the times after progression to mFOLFIRINOX I've seen attendings prefer a 2L systemic approach. Can give more details if useful

If disease is localized and hasn't responded well enough to proceed with surgery, SBRT or chemoRT are both reasonable things to consider. There's no good guiding data for which to choose over the other. And it's likely not going to get them to resectability. But it could kick the can down the road a bit. I typically do this to avoid switching cytotoxic chemo when you've really only got 2 options available.

There is new data for using SBRT (ablative RT) after induction chemo in technically resectable (but not surgery-worthy) pancreatic cancer.