ASH 2020 Day 3
Dec. 7th at ASH 2020, started at 7 AM on the west coast with 6 clinically important oral abstracts.
We will be posting interviews with 3 of the 5 lead investigators (Mato, Siddiqi, and Wierda) over the next few weeks, but today we share the breaking news on 2 exciting experimental novel therapies and 3 CAR-T trials, plus 1 discouraging real world look at the care that CLL patients are getting in the community.
First out of Israel, Dr. Benjamini from Chaim Sheba Medical Center in Israel presented: Efficacy of CD19-CAR T Cells in Richter’s Transformation after Targeted Therapy for Chronic Lymphocytic Leukemia (Paper ID: 545)
Richter’s Transformation has a dismal prognosis so when 6 of 9 patients in this study responded and the adverse events were mostly manageable, that is very good news. We don’t know why this CAR-T works so well, but maybe it is because it is produced in only 10 days locally and is “fresh’, never frozen.
The other 2 CAR-T oral presentations were concerning liso-cel (Lisocabtagene Maraleucel) with and without ibrutinib.
Dr. Weirda from MDACC presented: Transcend CLL 004: Phase 1 Cohort of Lisocabtagene Maraleucel (liso-cel) in Combination with Ibrutinib for Patients with Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) Paper ID: 544
In this difficult-to-treat group there was a 95% (18/19) response rate. Most had undetectable measurable residual disease (uMRD). There were no deaths or severe levels of CRS (cytokine release syndrome) or neurological events
Dr. Tanya Siddiqi from the City of Hope shared a different cohort in the same trial: Updated Follow-up of Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Treated with Lisocabtagene Maraleucel in the Phase 1 Monotherapy Cohort of Transcend CLL 004, Including High-Risk and Ibrutinib-Treated Patients Paper ID: 546
Overall response rate was 82% and was mostly durable. At 12 months, 50% (n = 11/22) were still responding and only 2 of those responders progressed beyond 12 months.
Of those who received liso-cel after their disease had both progressed on BTKi and failed to respond to venetoclax, 4 of 6 progression events was due to RT (Richter’s Transformation) including some whose CLL was in a complete remission.
Dr. Mato of MSKCC was the lead author of: LOXO-305, A Next Generation, Highly Selective, Non-Covalent BTK Inhibitor in Previously Treated CLL/SLL: Results from the Phase 1/2 BRUIN Study Paper ID: 542
Loxo-305 is a new “reversable” BTK inhibitor and the exciting news here is that its “efficacy was independent of BTK C481 mutation status, the reason for prior BTKi discontinuation (i.e. progression vs intolerance), or other classes of prior therapy received (including covalent BTK inhibitors, BCL2 inhibitors, and PI3K-delta inhibitors)”.
Dr. John Gribben from Barts Center, UK talked about: Umbralisib Plus Ublituximab (U2) Is Superior to Obinutuzumab Plus Chlorambucil (O+Chl) in Patients with Treatment Naïve (TN) and Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL): Results from the Phase 3 Unity-CLL Study Paper ID: 543
Why this is important is that it involves a novel PI3Ki that causes less of the major problems such as colitis and pneumonitis seen with the other drugs in the class and is active and safe to use frontline.
Finally, Dr. Mato presented something very dear to my heart with his: Real-World Prognostic Biomarker Testing, Treatment Patterns and Dosing Among 1461 Patients (pts) with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) from the informCLL Prospective Observational Registry Paper ID: 547
His findings were disappointing and re-enforce the importance of our Test Before Treat campaign. Some highlights of his research:
- The registry fully enrolled with 1461 patients: 855 (59%) previously untreated and 606 (41%) relapsed/refractory (R/R) patients.
- Community-based practices enrolled 93% of patients.
- FISH testing was performed in 28%.
- TP53 mutation testing was performed in 11%
- IGHV mutational status testing was performed in 12%
- 1/3rd of those not tested for TP53 and 1/3rd of those who didn’t have a FISH test received chemo-immunotherapy (CIT), which is like driving with a blindfold on.
- Of the patients with high-risk features, 28% received CIT, including almost 2/5th of the patients with unmutated IGHV suggesting a significant knowledge gap as CIT is not indicated in this group due to its poor activity.
Clearly, we have our work cut out for us. It doesn’t matter how great all these treatments are if the doctors are not recommending them and doing proper testing.
Finally, I want to again acknowledge how great it is to hear all the doctors thank the patients and their families. I remember when those word were so rare an event that I would sometimes go up to the microphone at prior ASH meetings and before asking my question to the speaker on the abstract, I would complement the researcher who had thanked the patients who had participated in the trial.
Tomorrow is the last day of ASH, and there will be little CLL news, so I will catch up on some of the important poster and biological presentations that we skipped before.
Thanks for watching. My video monologue does a deeper dive into the data.
Stay strong, we are all in this together