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A single low-dose infusion of ciltacabtagene autoleucel (cilta-cel), an autologous chimeric antigen receptor (CAR) T-cell therapy, was safe and associated with early, deep, and durable responses in patients with heavily pretreated multiple myeloma, according to research reported at the American Society of Hematology (ASH) virtual meeting.

In this exclusive 番茄社区 video, study author , of Mount Sinai Medical Center in New York City, discusses the .

Following is a transcript of her remarks:

CARTITUDE-1 is [a trial of] JNJ-4258 or cilta-cel, now known as ciltacabtagene autoleucel, a chimeric antigen receptor T-cell therapy with two BCMA [B-cell maturation antigen]-binding domains. At the past meetings, we presented the phase Ib portion of the CARTITUDE-1 study, and today I'll be reporting the combined results from the phase Ib/II study of CARTITUDE.

The primary objective of the phase Ib was to characterize the safety of cilta-cel and confirm its recommended phase II dose. The primary objective of the phase II was to evaluate its efficacy. To be eligible in this study, some of the key eligibility criteria where patients had to have progressive multiple myeloma per IMWG [International Myeloma Working Group], they had to have good performance status, measurable disease, and have been exposed to at least three or more prior therapies, including a PI [proteasome inhibitor], an IMiD [immunomodulatory drug], and an anti-CD38 antibody.

Once the patients were screened, they underwent bridging chemotherapy as needed, and they were then given lympho-depleting chemotherapy with fludarabine and Cytoxan from day -5 to day -3, then were infused with cilta-cel at a target dose of 0.75 million CAR-T cells per kg of body weight.

We enrolled a total of 97 patients in the combined phase Ib/II portion of this study, with a median age of 61, and over a little over half were male. You can see that these patients were heavily pretreated as their [number of] median prior lines of therapy was six and it ranged anywhere from three to 18 prior lines.

87% of these patients were triple-class refractory, and 42% were penta-refractory. One other interesting thing was this study did not require you to be refractory to your last line of therapy; however, 99% of the patients were indeed refractory to their last line of therapy.

The most common complication you expect with CARTITUDE or any CAR-T product is cytokine release syndrome [CRS] and neurotoxicity. First let's talk briefly about the CRS profile on this study. A majority of the patients -- so over 95% of these patients -- had grade 1 and 2 CRS, with about 5% of the patients having no CRS at all.

The median time of onset of CRS was 7 days, which is slightly different from the other CAR-Ts that are around ... which ranges anywhere from a day to 3 days. And there are supportive measures used to treat CRS and all but one patient had resolution of their CRS symptoms.

The interesting factor is that the cilta-cel CAR-T cell showed maximum peripheral expansion at a median of about 13 days.

Another thing I wanted to point out was that even though the time of onset of CRS was 7 days, and day 4 or later, we saw 89% of the patients, and day 6 or later, CRS happened in about 74% of these patients. CARTITUDE is being studied in an outpatient setting for CARTITUDE-2 and -4 studies.

When you get to neurotoxicity and other common complications seen with CAR-T cell therapies, we saw any grade neurotoxicity was about 21%, with grade 3 or higher being about 10%. We did split the CAR-T cell neurotoxicity into two groups -- one fit into ICANS [immune effector cell‐associated neurotoxicity syndrome], and the other was other neurotoxicities. And there was significant overlap between both of these groups.

The 16 patients who had ICANS all had resolution of their symptoms, and their ICANS was mostly grade 1 and 2. We had 12 patients who developed other neurotoxicities, including movement and neurocognitive changes, nerve palsy, and poor peripheral motor neuropathies. Half of these patients had complete resolution of their symptoms, and six patients did not resolve in their neurotoxicities.

One interesting thing to note is that we dosed an additional 50 patients in the subsequent CARTITUDE developmental programs, such as CARTITUDE-2, -4, and nine patients in the CARTITUDE-1 Japanese cohort, and we actually saw no additional movement in neurocognitive changes.

When we get to response rates, we know that the patients with relapsed/refractory myeloma have an overall survival, according to the MAMMOTH study, especially if you're a penta-refractory, of less than 6 months. And here we saw that the overall response rate in these patients was 97%, with 67% of these patients having stringent CR [complete response] and 93% of these patients having VGPR [very good partial response] or better.

And what's more interesting is that these responses are ongoing in 70 patients at the time of data cutoff, which was 12.4 months. And MRD [minimal residual disease] was evaluated in these patients, and out of the evaluable patients, 93% of these patients were actually MRD-negative at 10^-5.

Another interesting thing is the PFS [progression-free survival]. We all look for PFS when we're looking at clinical trials. And what we saw is that the median overall PFS is still not reached at a median duration of 12.4-month follow-up.

Interestingly, we tried to break down the PFS by best response to see if we reached a median PFS at that time. And we also saw, 12-month PFS if patients were in stringent CR was 85% and the 12-month PFS for patients in VGPR is 68%. Once again, we did not reach the median PFS, even by response rate. We saw that the 12-month overall survival rate was 89%.

So in conclusion, cilta-cel has a manageable safety profile at the recommended phase II dose, with mostly grade 1 and 2 CRS with neurotoxicity happening in about 20% of the patients. We also saw that this is a low dose of cilta-cel, but it yielded early, deep, and durable responses in this heavily pretreated patient population with an overall response rate of 97%, and stringent CR rates of 67%.

We saw that the median PFS is not reached, and the 12-month PFS rate was 77%.

In addition, cilta-cel is currently being investigated in earlier populations in myeloma patients and earlier-line settings, in particularly CARTITUDE-2 and 4 studies.

Thank you.

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