Thread by @HadidiSamer

Check out our correspondence for the real world data on the use of ide cel #mmsm @JCO_ASCO @ASCO @UAMSMyeloma @uamscancer

Intent Matters: Real-World Applicability of ide-cel Usage in the United States

➡️ascopubs.org/doi/10.1200/JC…

Led by @rajshekharucms @columbiacancer

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✅Violation of intent to treat principle

🛑17 of 196 (~9%) of patients who did not proceed to CAR T-cell infusion because of either disease progression/death (n = 12) or manufacturing failure (n = 5) were excluded from the final efficacy analysis👇

➡️ It is important to note that excluding pts who progress while waiting for CAR-T will not reflect the actual real world efficacy of CAR-T therapy
🛑We are adding layers of selection bias:
✅intent to manufacture
✅intent to treat
Notice the PFS/OS curves👇

🛑 Excluding pts who progress while waiting creates an inaccurate estimate to what is the real efficacy

🛑Unfortunately this was done in clinical trials, our hope was not to see it done in real world reporting

➡️we reported

nature.com/articles/s4140…

🛑 Among patients with RRMM listed for commercial BCMA CAR-T therapy,the 12-month cumulative incidence of receiving CAR-T therapy was low at 40% and of mortality of 26%
🛑About 1 in 4 patients died waiting for CAR-T therapy in our analysis

This was also shown by @Taxkourel where patients wait on an average of 6 months before apheresis and a quarter of patients unfortunately died while waiting for CAR T

pubmed.ncbi.nlm.nih.gov/36681151/

➡️It is important that real world data reflects actual real world practice and report outcomes on all patients without exclusion which adds to the selections bias unfortunately done by the clinical trials we have so far

✅status of being refractory to treatment

🛑 approximately two thirds of patients had refractory disease in the report compared to all pts in KarMMa

✅Higher percentage of utilization of stem cell boost

➡️In KarMMa trial, only two patients (2%) required autologous stem-cell boost,whereas in this study, 5% of patients were reported to require stem-cell boost

It is also important that previous report (from 3 centers in the same consortium) reported the use of stem-cell boost in 8% of included patients at a median of 54 days after CAR T-cell infusion at a median cell dose of 3.12 million cells/kg.

pubmed.ncbi.nlm.nih.gov/35939783/

➡️ Future real-world studies should also report data on the proportion of patients with stored autologous stem cells before CAR T-cell therapy in addition to those who end up receiving it

✅Lack of reporting of racial composition of patients

🛑 Current report did not provide data on racial/ethnic composition of patients

We reported significant racial and geographical disparities for myeloma patients considered for CAR-T products

jamanetwork.com/journals/jaman…

We believe it is important for all journals including @JCO_ASCO @ASCO to ensure racial composition is being reported as part of patient characteristics in all future publications.

We concluded by:

“Although we strongly believe that the use of real-world reports on efficacy and toxicity of CAR T-cell therapy is important, caution must be exercised when reporting outcomes for highly selected patients since they may not correctly reflect the ground reality.”

Here is the full paper:

And here is the authors reply:

ascopubs.org/doi/abs/10.120…

We appreciate their hard work and hope future reports will reflect improved reporting of real world data to reflect what we deal with in real life