clinical cases

This forum made possible through the generous support of SDN members, donors, and sponsors. Thank you.
Advertisement - Members don't see this ad
42 year old.

Bilateral renal masses, biopsy proven ccRCC (called low grade on path).

The left mass is so large it needs radical nephrectomy. The right mass is borderline.

She’s seeing me for neoadjuvant treatment to shrink them before urology goes in.

I like the idea of dual IO in young people because it’s the best chance of a durable response, but the response rate is lower than IO/TKI.

Would anyone do “neoadjuvant” dual IO, or do you prioritize the ORR of TKI’s in this setting? I’m leaning toward IO/TKI - either Cabo/nivo or if the patient is ok with the toxicity, Len/pembro.
 
42 year old.

Bilateral renal masses, biopsy proven ccRCC (called low grade on path).

The left mass is so large it needs radical nephrectomy. The right mass is borderline.

She’s seeing me for neoadjuvant treatment to shrink them before urology goes in.

I like the idea of dual IO in young people because it’s the best chance of a durable response, but the response rate is lower than IO/TKI.

Would anyone do “neoadjuvant” dual IO, or do you prioritize the ORR of TKI’s in this setting? I’m leaning toward IO/TKI - either Cabo/nivo or if the patient is ok with the toxicity, Len/pembro.
I would probably do what you’re doing. We love the idea of those sustained CRs with dual IO but in reality it’s like… 10-15%?

If it is the chance or staying off dialysis I’d probably lean toward IO/TKI. Response rates are higher and you’re still getting exposure to IO anyway.
 
I would probably do what you’re doing. We love the idea of those sustained CRs with dual IO but in reality it’s like… 10-15%?

If it is the chance or staying off dialysis I’d probably lean toward IO/TKI. Response rates are higher and you’re still getting exposure to IO anyway.
I agree, while in the metastatic setting there is a good argument for io/io, I would do pembro lenva for cytoreduction prior to surgery, especially if there is no sarcomatoid differentiation.

I'm sure you are planning this, but would make sure he has genetic testing. Likelihood >10% you'll find something.
 
Just a brief Lenvatinib update regarding my earlier question on len-pembro for ccRCC: I hate this drug.

1) A CLL case (mal heme is my weak area, and I'm covering for a partner - so pardon how simple of a question this is)
- 80 year old. CLL treated with obinutuzumab and venetoclax 4 years ago with excellent response. Counts normalized for 4 years. Earlier in 2026, WBC starting rising, almost entirely lymphocytosis. 40K --> 100K. Platelets now down to 50K. ANC is now < 1. New anemia. LDH 550 and uric acid 12. No blasts on smear. Flow pending.

CT CAP with new upper abdominal nodes.

The question here is Richter's Transformation vs just relapsed CLL, right? The textbook right answer is PET him and then get excisional biopsy I believe but this is inpatient and can't get a PET. Also, he's too sick to get an abdominal surgery to go after the abdominal nodes - I don't think they're accessible percutaneously.

Would a bone marrow be an appropriate replacement?

2) ccRCC case. Good performance status 55 year.
--- Nephrectomy 2024 with 1 year adjuvant pembro ending July 2025.
-- Oct 2025, developed small thigh mas on PET with her previous oncologist.
-- PET with me 3/2026: growing thigh mass and small hip lytic lesion --> very small volume of disease.
-- Thigh mass removed, confirmed as ccRCC.

So I have a lady with oligorecurrent disease -- one of which has been surgically excised. The other area is amenable to SBRT.

My options are:
1) IO-IO ---> I am a bit concerned about IO/IO rechallenge since she relapsed so soon after end of pembro, though it's low volume recurrence
2) IO-TKI --> this is not curative (at least likely than IO/IO)
3) SBRT perhaps then "adjuvant" IO/TKI?
 
Last edited:
Just a brief Lenvatinib update regarding my earlier question on len-pembro for ccRCC: I hate this drug.

1) A CLL case (mal heme is my weak area, and I'm covering for a partner - so pardon how simple of a question this is)
- 80 year old. CLL treated with obinutuzumab and venetoclax 4 years ago with excellent response. Counts normalized for 4 years. Earlier in 2026, WBC starting rising, almost entirely lymphocytosis. 40K --> 100K. Platelets now down to 50K. ANC is now < 1. New anemia. LDH 550 and uric acid 12. No blasts on smear. Flow pending.

CT CAP with new upper abdominal nodes.

The question here is Richter's Transformation vs just relapsed CLL, right? The textbook right answer is PET him and then get excisional biopsy I believe but this is inpatient and can't get a PET. Also, he's too sick to get an abdominal surgery to go after the abdominal nodes - I don't think they're accessible percutaneously.

Would a bone marrow be an appropriate replacement?

2) ccRCC case. Good performance status 55 year.
--- Nephrectomy 2024 with 1 year adjuvant pembro ending July 2025.
-- Oct 2025, developed small thigh mas on PET with her previous oncologist.
-- PET with me 3/2026: growing thigh mass and small hip lytic lesion --> very small volume of disease.
-- Thigh mass removed, confirmed as ccRCC.

So I have a lady with oligorecurrent disease -- one of which has been surgically excised. The other area is amenable to SBRT.

My options are:
1) IO-IO ---> I am a bit concerned about IO/IO rechallenge since she relapsed so soon after end of pembro, though it's low volume recurrence
2) IO-TKI --> this is not curative (at least likely than IO/IO)
3) SBRT perhaps then "adjuvant" IO/TKI?

Really tough case and an area where there is not much data. Just thinking out loud:
1. Is this imdc favorable risk (assuming the rest of the lab values are normal)? Who knows... recurrence was relatively quick after adjuvant IO, but did the pembro change the natural history of this disease (i.e. how do we measure time to systemic therapy - from diagnosis or from end of adj therapy)? Who knows...
2. After sbrt, you have no measurable disease. What are you treating and how do we measure efficacy/overtreatment? Is active surveillance a reasonable option? (For the record I agree with SBRT)
3. Real world data post adjuvant pembro followed by io combination - looked like we may be converging on 6 months as a reasonable target for rechallenge. However, this person recurred 3 months post but is now >6 months when they will receive treatment. Where does this patient's benefit lie in rechallenging with IO/tki or io/io? (Im guessing towards less benefit)
3. Low volume disease - as you point out, is this the type of patient where you have the luxury of a trial of io/io whether it works or not? But the risk of life altering toxicity is not negligible...
4. I think the biology of this disease is aggressive and I would advocate for treatment rather than active surveillance.

If it were my patient, I would explain the above and get a feel for what they want. We have time as they will get SBRT and then come back with repeat CT. If truly nothing, the convo will be long. If tiny lung nodules start appearing, I would guide towards 1L IO/IO -> 2L cabozantinib in a 55 yo who tolerated pembro well.

Would love to hear others' thoughts!
 
Just a brief Lenvatinib update regarding my earlier question on len-pembro for ccRCC: I hate this drug.

1) A CLL case (mal heme is my weak area, and I'm covering for a partner - so pardon how simple of a question this is)
- 80 year old. CLL treated with obinutuzumab and venetoclax 4 years ago with excellent response. Counts normalized for 4 years. Earlier in 2026, WBC starting rising, almost entirely lymphocytosis. 40K --> 100K. Platelets now down to 50K. ANC is now < 1. New anemia. LDH 550 and uric acid 12. No blasts on smear. Flow pending.

CT CAP with new upper abdominal nodes.

The question here is Richter's Transformation vs just relapsed CLL, right? The textbook right answer is PET him and then get excisional biopsy I believe but this is inpatient and can't get a PET. Also, he's too sick to get an abdominal surgery to go after the abdominal nodes - I don't think they're accessible percutaneously.

Would a bone marrow be an appropriate replacement?

2) ccRCC case. Good performance status 55 year.
--- Nephrectomy 2024 with 1 year adjuvant pembro ending July 2025.
-- Oct 2025, developed small thigh mas on PET with her previous oncologist.
-- PET with me 3/2026: growing thigh mass and small hip lytic lesion --> very small volume of disease.
-- Thigh mass removed, confirmed as ccRCC.

So I have a lady with oligorecurrent disease -- one of which has been surgically excised. The other area is amenable to SBRT.

My options are:
1) IO-IO ---> I am a bit concerned about IO/IO rechallenge since she relapsed so soon after end of pembro, though it's low volume recurrence
2) IO-TKI --> this is not curative (at least likely than IO/IO)
3) SBRT perhaps then "adjuvant" IO/TKI?
Def want to r/o richters. PET with excisional as you mentioned is gold standard. Sure go for marrow but it’s subject to sampling error just like a random nodal bx is (without pet)
 
Advertisement - Members don't see this ad
Just a brief Lenvatinib update regarding my earlier question on len-pembro for ccRCC: I hate this drug.
I told you.
1) A CLL case (mal heme is my weak area, and I'm covering for a partner - so pardon how simple of a question this is)
- 80 year old. CLL treated with obinutuzumab and venetoclax 4 years ago with excellent response. Counts normalized for 4 years. Earlier in 2026, WBC starting rising, almost entirely lymphocytosis. 40K --> 100K. Platelets now down to 50K. ANC is now < 1. New anemia. LDH 550 and uric acid 12. No blasts on smear. Flow pending.

CT CAP with new upper abdominal nodes.

The question here is Richter's Transformation vs just relapsed CLL, right? The textbook right answer is PET him and then get excisional biopsy I believe but this is inpatient and can't get a PET. Also, he's too sick to get an abdominal surgery to go after the abdominal nodes - I don't think they're accessible percutaneously.

Would a bone marrow be an appropriate replacement?
Too sick for an excisional biopsy and hospitalized? Probably too sick for aggressive treatment too. Marrow is an answer, but I don't think it's a good one. If I could get rituximab as an inpatient (which I can't), I'd give a dose of that, maybe some steroids and hope to temporize him enough to get discharged and the appropriate workup done.
2) ccRCC case. Good performance status 55 year.
--- Nephrectomy 2024 with 1 year adjuvant pembro ending July 2025.
-- Oct 2025, developed small thigh mas on PET with her previous oncologist.
-- PET with me 3/2026: growing thigh mass and small hip lytic lesion --> very small volume of disease.
-- Thigh mass removed, confirmed as ccRCC.

So I have a lady with oligorecurrent disease -- one of which has been surgically excised. The other area is amenable to SBRT.

My options are:
1) IO-IO ---> I am a bit concerned about IO/IO rechallenge since she relapsed so soon after end of pembro, though it's low volume recurrence
2) IO-TKI --> this is not curative (at least likely than IO/IO)
3) SBRT perhaps then "adjuvant" IO/TKI?
SBRT and observe? That's probably where I'd go, especially since you know she's going to get more systemic therapy relatively soon. Save it for when local therapy isn't an option anymore.
 
78F, ECOG 1. Met serous ovarian cancer. BRCA1 only targetable mutation (somatic, not germline). Has progressed on carbo/taxol/bev --> olaparib/bev maintenance (18 months on that regimen); Carbo/Doxil (only 3 months), then switched to Cytoxan/Pembro/Bev but had to stop after C3 because of Grade 3-4 immune mediated aplastic anemia (probably should have admitted her but she refused). Currently on a long pred taper with decent response but has persistent anemia. WBC and plts have normalized.

CT scan after just those 3 cycles showed a pretty good response. I'm planning another one once I get her off steroids, probably another month or so.

I do tend to re-challenge most of my irAEs when clinically appropriate, but I'm fairly hesitant about this one since I'm worried about her ability to survive me nuking her marrow a 2nd time.

Where would people turn for 4th line therapy in a case like this. I know there are about a dozen things I can choose, most of which won't work. I don't treat a ton of gyn stuff so appreciate folks' input.
 
78F, ECOG 1. Met serous ovarian cancer. BRCA1 only targetable mutation (somatic, not germline). Has progressed on carbo/taxol/bev --> olaparib/bev maintenance (18 months on that regimen); Carbo/Doxil (only 3 months), then switched to Cytoxan/Pembro/Bev but had to stop after C3 because of Grade 3-4 immune mediated aplastic anemia (probably should have admitted her but she refused). Currently on a long pred taper with decent response but has persistent anemia. WBC and plts have normalized.

CT scan after just those 3 cycles showed a pretty good response. I'm planning another one once I get her off steroids, probably another month or so.

I do tend to re-challenge most of my irAEs when clinically appropriate, but I'm fairly hesitant about this one since I'm worried about her ability to survive me nuking her marrow a 2nd time.

Where would people turn for 4th line therapy in a case like this. I know there are about a dozen things I can choose, most of which won't work. I don't treat a ton of gyn stuff so appreciate folks' input.
If grade 3 requiring long term steroids or grade 4 A/E then I won't rechallenge with IO. Can bring it later if you run out of options.
That being said, check for FOLR1 IHC - Mirvetuximab soravtansine is an option (ocular s/e hence baseline eye exam), relacorilant with Abraxane (new approval), single agent chemos (gem, Abraxane etc.).
 
If grade 3 requiring long term steroids or grade 4 A/E then I won't rechallenge with IO. Can bring it later if you run out of options.
That being said, check for FOLR1 IHC - Mirvetuximab soravtansine is an option (ocular s/e hence baseline eye exam), relacorilant with Abraxane (new approval), single agent chemos (gem, Abraxane etc.).
No FOLR1 or anything targetable. I completely forgot about relacorilant/abraxane. Thanks for the reminder.
 
So I am relatively early in my career and have had a few asking me about Daraxonrasib for Pancreatic Cancer, I guess it was recently approved for “expanded access” FDA Permits Expanded Access for Investigational Pancreatic Cancer Drug

Does anyone have experience with programs like that and whether a community or PP Onc doc could realistically get their patients on these drugs?
I sent a request for a patient of mine last week and got the reply with the paperwork yesterday afternoon. I'll get to work on it next week.

I've never personally done it, but do know some folks in academ-ish practice that have been successful with it in the past.

I think this one is going to be a horse of a different color though. If these data are real, this drug is absolutely game changing in pancreatic cancer. In my experience, met panc clinical trials are phenomenally easy to recruit to because the available options suck so badly and it's such a terrible disease. This company is going to be absolutely pummeled with these requests. We'll see how they hold up under the pressure.
 
Advertisement - Members don't see this ad
Appreciate the input, are you guys waiting for progression on 5FU-based + Gem/Abraxane? Or just after 1 line?
The study was 2nd line or beyond so I'm going to request it on anyone who's progressed on at least one line of therapy.

The one I've got in the pipeline already is actually on 5FU maintenance after a pretty good response to FOLFIRINOX for 6 months.

I rarely do maintenance in pancreatic but he couldn't keep going on FOLFIRINOX and didn't need to change treatment yet. I suppose if they really pushed me, I could spin this as 2nd line when he fails.

Since I have no idea what the timeline or amount of work it's going to take to get this available is yet, I'm just doing it somewhat proactively on a couple of people. I think I'll have better luck than many in getting EAP access since I can plead "poverty" since it's only supposed to be for people with no access to active clinical trials. Since I'm rural CAH, I'm going to use that to my advantage.