CARTITUDE-1 Study Results Show Promise for Patients with Relapsed/Refractory Multiple Myeloma

CancerNetwork talked with Jesus G. Berdeja, MD, of the Sarah Cannon Research Institute regarding the CARTITUDE-1 study that examined CAR-T cell therapy to treat patients with relapsed/refractory multiple myeloma presented at the 2020 ASCO Virtual Scientific Program.

CancerNetwork: Could you provide a brief summary of the CARTITUDE-1 study that you conducted?

Berdeja: I had the pleasure of presenting the CARTITUDE-1 study at this year’s ASCO Meeting. This is a phase 1b/2 study of JNJ-4528 which is a BCMA-directed CAR T(-cell) therapy in relapsed/refractory multiple myeloma patients. JNJ-4528 is a traditional second-generation CAR T(-cell) therapy that has a cd3 zeta signaling domain and 41bb costimulatory domain. What makes it different from the other BCMA CAR-T’s is that it has 2 BCMA-targeting single chain antibodies and this is thought to confer more avidity. Its identical to the CAR construct that was used in the LEGEND 2 study.

The CAR T dose administered for this CAR T was also lower than traditionally done with other BCMA products. The median administered dose was 0.72x106 CAR-positive viable T cells per kilogram which roughly is about 50 to 60 million, if you want to compare. Basically, we presented the results of the phase 1b portion and these were 29 patients that were heavily pretreated with median 5 prior lines of therapy. The patients did well, and we saw no unexpected safety signals. Most patients had cytokine release syndrome (CRS) as expected, but mostly grade 1/2. Very few patients had grade 3 or higher CRS. In the median time of onset of CRS was 7 days, which is a little bit longer than some of the other BCMA products. Neurotoxicity was very infrequent, and generally low-grade as well with only 1 grade 3 event. We did see cytopenias in virtually all the patients but most result by 60 days and there was low incidence of any infectious complications.

The product works quite well. It had an overall response rate of 100%. Eighty-six percent of the patients had stringent complete remissions and 97% of the patients had at least a VGPR or better at a median follow-up of 11.5 months. There were 16 patients in complete remission that also had MRD assessment and of these 81% were MRD negative at 10-5 and 69% were MRD negative at 10-6. The progression-free survival at 9 months was 86% and based on this JNJ-4528 has received breakthrough therapy designation. The phase 2 portion of this study is fully enrolled, and we can’t wait to show you the results.

CancerNetwork: What is the main takeaway you want professionals to see from this study and the corresponding data?

Berdeja: I think it’s very impressive data in this patient population. I’ll remind us that in relapsed/refractory multiple myeloma the drugs that have been approved for this indication had response rates of about 30% with PFS of about 4 months. So, these types of responses are just unprecedented, and I think it’s in keeping with what we’ve seen with other BCMA products. I would say the depth of response here so quickly is actually quite impressive. I think the other thing that’s make this a little bit different is again like we’ve seen with other BCMA products its relatively well tolerated compared to the earlier cd-19 products, but also the time of onset of CRS here is very different. It’s a little bit delayed, about a week into it which may allow this to be dosed as an outpatient which I think will be a significant difference from our standard.

CancerNetwork: How does this data change the way professionals will go about treating multiple myeloma?

Berdeja: I think this is no doubt one of the lead products to become FDA approved for multiple myeloma. I think this is one of the first products that will be available hopefully to most of us. I think it will change significantly the current treatment paradigm of relapsed/refractory myeloma. Obviously at this point that’s not the case yet but I think it’s coming soon.

CancerNetwork: What are the next steps for phase 2 following the results of the 1b study?

Berdeja: I think what everyone is interested in is we’ve seen these great responses and the question is durability. Unfortunately, with the more advanced products so far, we are not seeing a flattening of the curve like we saw with lymphoma and leukemia. We were a little bit disappointed form that standpoint, but a PFS of close to a year is still quite impressive in this patient population. I think what I’m really hoping to see is that this will translate a little more, and maybe behave more like the LEGEND 2 data that was presented before. If you look at the LEGEND 2 data they presented at ASH, the most recent PFS is about 20 months and that’s obviously quite impressive. Of course, the patient population was not the same, so the question is will it translate to this population. So far, what we’re seeing is the response rates and safety data has all behaved very similarly to what the LEGEND 2 study has shown. Hopefully it will be the same with the long-term data.

CancerNetwork: Is there anything I haven’t asked that you wanted to discuss regarding this research?

Berdeja: The only thing I would mention is that like with everything else in myeloma we think this will probably work better in earlier lines of therapy. There are phase 2 and 3 studies being planned in earlier lines of therapy for myeloma patients. My suspicion is that CAR T will not be the last therapy used in patients in the near future.