Parameswaran Hari, MBBS, MD, Medical College of Wisconsin, Milwaukee, discusses results from a study assessing the cost of cytokine release syndrome (CRS) and neurotoxicity management for patients with relapsed/refractory multiple myeloma (MM) who received CAR-T therapy in the KarMMa trial.
These results were presented at the virtual 62nd American Society of Hematology (ASH) Annual meeting.
Transcript
Hi, my name is Parameswaran Hari. I'm a professor of medicine at the Medical College of Wisconsin in Milwaukee. I'm happy to introduce this poster that was presented at ASH on Saturday.
The study is looking at the health care resource utilization and the costs to the more specific toxicities associated with CAR-T therapy in multiple myeloma. This is a sub-study or an ancillary study of the major data presented for the KarMMa clinical trial.
The KarMMa clinical trial is a mature trial. It was a phase 1/2 study of bb2121, also known as ide-cel, which is a BCMA-targeted CAR T-cell therapy for patients with relapsed and refractory multiple myeloma. The data about the main study has been published with initial results and then presented at ASCO and EHA. It's very mature now.
We investigated the health care resource utilization and the costs associated with the specific toxicity of CAR-T therapies, which is cytokine release syndrome and neurotoxicity. These are unique toxicities generic to the CAR-T platform.
The objective was to find out health care resource utilization associated with these 2 toxicities in the relapsed/refractory myeloma setting and for the ide-cel CAR T-cell treatment.
Essentially, the costs were assigned based on national payer databases, and toxicities were identified from the study database. The dates of onset and resolution were also identified from the clinical trial database, and the management guidelines for cross-check to show that the resource utilization was truly associated with the CRS or neurotoxic side effects specifically.
Various CMS and other Physician Fee Schedule databases were looked at for the diagnostic tests, laboratory studies, transfusion, ventilation, dialysis, all the other medical interventions that were used to support patients during these side effects.
The top-line data are that the majority of cytokine release syndrome or CRS seen in the study was grade 1 and 2 as small number were grade 3 and 4. Majority of neurotoxicity seen in this study was associated with CRS and, again, with lower level of CRS and neurotoxicity. Neurotoxicity more than grade 3 was only seen in 4 individuals or 3.7% of the cases.
There were no patient demographic-related variables that predicted who was going to get these toxicities and what grade. However, patients were on 2 different doses, 300 million or 450 million CAR T-cells, and the actual dose of cells received did not seem to matter in terms of the grade or severity of CRS and neurotoxicity.
Health care resource utilization increased as the severity of the CRS or CRS and neurotoxicity increased. With a grade 1 and 2 CRS being associated with $18,000 to $23,000 in terms of extra health care resource utilization, Grade 3 being associated with almost $60,000, and grade 4, which was just one case, associated with $120,000.
Similarly, for CRS and neurotoxicity occurring together, grade 2 or below associated with the cost of what $33,000. Grade 3 either CRS or grade 3 neurotoxicity occurring together was $90,000 to $215,000. Essentially, the costs were driven by the grade.
Grade 2 or below were associated with significantly lower costs in the range of $20,000 to $30,000, and the Grade 3 and above were associated with much higher costs. The jump was pretty stark. This is the primary conclusion of the study.
What follows is that the ICU stay was the key driver of these costs. The ICU stay in the patient who had grade 4 CRS, for example, was 24 days, whereas grade 1 and 2 was only 6 days. That necessarily meant there were other interventions done in the ICU, which also raised up the cost.
CAR-Ts that are associated with lower grades of CRS or neurotoxicity or both will be associated with lower health care resource utilization. Another corollary would be that if patients get early CRS or neurotoxicity, early intervention, to keep it at a Grade 1 or 2 level, will also lead to significant cost savings, and let it progress to grade 3. This is our conclusions from this study.
