Doris Hansen, MD, Assistant Member in the Moffitt Cancer Center Department of Blood and Marrow Transplant and Cellular Immunotherapy, discusses the treatment of multiple myeloma using daratumumab, lenalidomide, and dexamethasone (D-Rd) and bortezomib, lenalidomide, and dexamethasone (V-Rd) in transplant-ineligible patients.
Transcript:
So my name is Doris Hansen, I’m from Moffitt Cancer center. I’m a myeloma provider here at Moffitt. I focus in the bone marrow transplant space as well as immunotherapies. So very happy to be here and talk about the work. So the first abstract is comparison of time to next treatment between frontline daratumumab, lenalidomide, dexamethasone or D-Rd and bortezomib, lenalidomide, dexamethasone or V-Rd in transplant ineligible patients with multiple myeloma so commonly in current days.
So the way that myeloma is treated, a patient receives induction chemotherapy and followed by high dose chemotherapy such as melphalan and stem cell transplant. However, if patients are older and they’re more frail, they may not be eligible for a stem cell transplant. So the two treatment options that are preferred in the NCCN guidelines are D-Rd and V-Rd. So essentially we did the study to look at what is the time to next treatment between these two options. So D-Rd and V-Rd, but also to add to the evidence base regarding the comparative effectiveness between these two regimens for our patients.
So essentially in this study we used the Essentris database. So this database is a deidentified academic database and it’s used to collect information from 22 institutions from 14 different states. It’s used by over more than 100,000 providers. It’s a good database and it’s got significant information on medications particularly. So it was a good way to calculate time to next treatment.
In terms of how did we balance or how did we compare these two groups of treatments, we used a method or a statistical method known as the inverse probability of treatment, waiting to adjust baseline characteristics. In the end, we had 643 eligible patients who were able to include in the study 149 of these patients received D-Rd or daratumumab, lenalidomide, dexamethasone and 494 received V-Rd. After inverse probability of treatment weighted and adjusting characteristics between the two groups, we identified that the groups were fairly similar. There were some minor imbalances that were adjusted for in a w robust Cox model, but the mean age was 75. The Quan-Charlson Comorbidity Index was very similar between the two cohorts and less than half of the patients were female.
In terms of what did we find in the study? Right, so we found that frontline daratumumab, lenalidomide, dexamethasone is associated with a longer time to next treatment or death compared to V-Rd or bortezomib, lenalidomide, dexamethasone. We found that the use of frontline D-Rd was associated with a 42% lower risk of progressing or advancing to a subsequent therapy or dying compared to V-Rd, as evidenced by an adjusted hazard ratio of zero point 58. The median time to next treatment in patients receiving D-Rd was 38 months compared to 19 months in patients receiving V-Rd. Certainly the study has limitations, as any study does.
Our database is not perfect, so there are some missing information like ecog performance status or cytogenetics, but that may have helped to contextualize the findings. And I think it’s important to point out to the viewers that time to next treatment is not a direct proxy for progression free survival. It may be impacted by other factors and it does underestimate pfs and certainly there’s some administrative censoring and it is a provider based data source. But I think overall the study is very helpful in the sense that it does support existing evidence from, for example, the Taurus and the Pegasus essentially stating that D-Rd it’s supporting the use of D-Rd over V-Rd in frontline transplant ineligible patients and hopefully it will assist providers in making an informed decision making when choosing a therapy for patients with newly diagnosed multiple myeloma who are transplant ineligible. So yeah, this cost per responder analysis was for patients who were lenalidomide refractory who received cilta-cel on the clinical trial known as cartitude four.
So cell to cell was FDA approved in 2022 and it has shown superior efficacy compared to physicians choice like DPD or PVD and what I mean by superior efficacy, superior progression free survival response rate, complete response rate. However, the goal of the study was to identify what was the value of cilta-cel compared to physicians choice, not only accounting for clinical benefit but also cost wise. So we used the mixed payer source and Microsoft Excel to create a cost per responder model where we essentially accounted for cost of drug acquisition costs associated with apheresis, lymphodepletion prior to CAR T, CAr t infusion or cilta-cel infusion, as well as hospital costs for seven days, cost of managing immune mediated toxicities, subsequent therapies and prophylactic antibiotics. And we compared the cost as in the total cost, the cost per complete responder, as well as cost per month in progression free survival over approximately 25 month period. And essentially we identified that the total cost between cilta-cel and physician’s choice was approximately 700 versus 800,000 for patients receiving cilta-cel versus physician’s choice cost per complete responder was significantly lower.
With cilta-cel it was approximately a million over slightly over three and a half million, and then cost per month in progression free survival is approximately 30,000 versus 40,000. So as you can see, there is benefit, not only clinical but economic benefit in using cilta-cel versus physician’s choice. We also did a scenario where 30% of the patients were treated outpatient. As we see more and more these days, especially in large academic medical centers where patients are being treated outpatient with cilta-cel. And even in this model, we identified that there was benefit, economic benefit for patients as opposed to physicians choice.
So I’d say overall our study shows yes, cilta-cel is a great product, also not efficacy wilds, but especially in patients who have a complete response, we see a significant economic benefit, but we’re hoping that the study will also assist payers in seeing the true value of these novel therapies when accounting for clinical benefit and economic benefit when using cilta-cel as well, compared to the physician’s choice therapy. So for frontline practitioners, I’d say the first abstract. So the comparison of time to next treatment or death, essentially there’s been multiple studies. Like I said, the Taurus chart review, the other adjusted indirect comparison like Pegasus and now this study looking at time to next treatment, essentially showing that D-Rd appears to be superior to V-Rd, at least based on our study. So it does support the clinical effectiveness of using daratumumab, lenalidomide, dexamethasone over V-Rd in patients who are transplant and eligible with newly diagnosed multiple myeloma.
And again, hopefully we’ll help these clinicians make an informed decision when deciding what treatment to give to patients in the frontline setting. And then the other study, the cost per responder model. Hopefully, although CAR T can appear to be a very expensive treatment upfront, if you look at it over a 25 month period, as we did in the study, it has significant benefit clinically and economically, and hopefully will assist payers in approving this therapy for our patient when it is necessary because they can have significant benefit in multiple ways.
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