Linnea Olson's Best Next Treatment Option - External Review Board Meeting Recording [Linnea Olson Hackathon]

If you have time, please share any suggestions or questions on Linnea Ohlson’s treatment for her physicians (Jess Lin and Alice Shaw) by Thursday of this week. 

You can respond on our online forum (Slack), on the Linnea Treatment Options document, or by email.

In our special review meeting last night (Sunday), Linnea updated us on her situation, and we discussed her treatment options.

Current Situation: In the last week, Linnea has been suffering from fever, vomiting, difficulty breathing, pneumonia, and liquid on her lungs. She has been in and out of the emergency room for IV antibiotics and to have her fluid drained. She has stopped the phase 1 clinical trial she was on — a combination of lorlatinib and a SHP2 inhibitor – which started on June 10. She is staying on lorlatinib. It’s difficult to assess what is happening with the cancer due to the effusion clouding things. She will be getting a scan on Thursday. She will be getting a pleural cath. All of her tissue from her recent biopsy is gone.

Treatment Strategy: There is a general consensus from Linnea’s physicians, Ross Camidge (ALK expert), and many of the hackathon contributors, that the 4th generation ALK inhibitor drug being offered by Turning Point (TPX-0131), which will be available in the fall in a clinical trial at MGH, is the best next treatment option for Linnea. Kimary Kulig noted from her reading of the Caris report that Linnea is “Still highly ALK+ (IHC score 3+), but with a resistance mutation making continued lorlatinib therapy possibly futile = search for newer generation ALK inhibitors with at least preclinical evidence of working on the Exon 23 G1202R point mutation.” Jess Lin is concerned that the clinical trial will not provide a therapeutic dose.

Bridging Strategy: Linnea needs a bridging drug regimen to tide her over to the TPX-0131 (or cell-based) trial in the fall. Her physicians are suggesting a course of chemotherapy (and lorlatinib), which was also suggested by oncologists Ross Camidge and Luiz Raez, and endorsed by Mehrad Tavallai of Natera. Will LaValley asks about low dose chemo. Because of Linnea’s KEAP1 mutation and other test results, Kimary Kulig is skeptical that chemo will be effective. “KEAP 1 Exon 6 Y584fs point mutation = unlikely to respond well to chemotherapy or immunotherapy.”

Draft Questions for Linnea to Discuss with Jess Lin and Alice Shaw on Thursday

1. [Kimary Kulig] Chemo: Is chemo a viable bridging option given the KEAP1 mutation?

2. [Will LaValley] Chemo: Is low dose chemo a possible consideration?

3. [Kimary Kulig] Pathology: Were IHC stains done at MGH for N-Cadherin, Vimentin, Zeb 1, and LKB1?

4. [Kimary Kulig] Pathology: Is there anything that can be analyzed on the existing slide?

5. [Ally Perlina] Drug Options: What about avastin (bevacizumab), which correlates with sensitivity in this lung cancer type with TP53 alterations, + combined with a different ALK inhibitor (like alectinib or brigatinib) and + chemo (if appropriate/ relevant)?”

6. [Kimary Kulig]: Drug Options: Is KEAP1 druggable and is the Calithera drug a reasonable treatment option?

7. [Grace Cordovano, Kimary Kulig, Brad Power]: Care Partner: How can we offload some of the burden and decision-making for Linnea, e.g., have Kimary talk to Linnea’s pathologists and shepherd the tissue analysis. Does MGH have a HIPAA consent document Linena can sign, or is the form Kimary prepared acceptable?

What would you add, delete, or modify?

(Special apologies to everyone I mentioned above in the likely event that I have made mistakes in wording.)

Thanks,

Brad