CAR T-Cell Therapy on the Horizon in Multiple Myeloma

February 2020 Vol 11, No 2


Multiple Myeloma

Chimeric antigen receptor (CAR) T-cell therapy could soon be added to the treatment armamentarium in relapsed/refractory multiple myeloma. An investigational CAR T-cell therapy led to early and deep responses in heavily pretreated patients. In addition, all evaluable patients in the study reached minimal residual disease (MRD)-negative status. This comes from recently reported data from the phase 1b/2 CARTITUDE-1 trial, presented by Deepu Madduri, MD, at the 2019 ASH Annual Meeting.

Treatment advances in recent years have led to improved survival in patients with multiple myeloma, but CAR T-cell therapy has yet to be approved for this malignancy. In patients with relapsed/refractory disease in whom all approved therapeutic options have failed, median overall survival is less than 12 months.

The B-cell maturation antibody (BCMA) protein is overexpressed in myeloma, and the treatment used in the study—JNJ-4528—is a structurally distinct CAR T-cell therapy that contains 2 BCMA-targeting antibodies.

Dr Madduri presented results from the phase 1b portion of the study, in which median follow-up was 6 months at data cutoff.

Responses Seen in 100% of Patients

“Every single patient on the study responded to therapy, for an overall response rate of 100%, with 66% showing stringent complete responses,” said Dr Madduri, from the Icahn School of Medicine at Mount Sinai in New York City. “Considering these patients have all received multiple prior therapies, these results are extremely encouraging.”

Patients with progressive disease (as well as measurable disease in their blood or bone marrow), who had previously received at least 3 prior therapies and all 3 classes of available agents (a proteasome inhibitor, an immunomodulatory drug, and CD38 therapy), were eligible to enroll in the trial. Dr Madduri noted the highly refractory nature of the study population: the median number of prior lines of therapy was 5, ranging from 3 to 18.

After enrollment, T cells were collected from patients and genetically reengineered to express JNJ-4528. Following lymphodepleting chemotherapy (to wipe out T cells so the newly engineered cells can move in and do their job), patients underwent reinfusion of the new cells.

In total, 29 patients with a median age of 60 years were infused with JNJ-4528 at a median administered (weight-based) dose of 73,000 CAR T cells.

“If you break the 100% response rate down further, you see that 69% of patients were in complete response, meaning they had no evidence of myeloma cells in their bone marrow or blood, while 86% of patients were in very good partial remission or better,” Dr Madduri reported.

The median time to first response was 1 month, as was the median time to complete response or better. Of 17 evaluable patients, all 17 were MRD negative. At data cutoff, 27 of 29 patients remained progression free.

As expected, the most common grade 3/4 adverse events were hematologic, and nonhematologic adverse events were very uncommon. All but 2 patients experienced cytokine release syndrome (CRS), the majority (86%) being grade 1/2. The median time to onset of CRS was 7 days, setting JNJ-4528 apart from other CAR T-cell therapies that typically lead to CRS within the first few days of treatment.

“It was thought initially that CAR T-cell therapy was going to cure these patients,” added Dr Madduri. “Maybe ‘cure’ isn’t the right word yet, but perhaps we can give a 1-time treatment for these patients who come once or twice a week for infusions.”

The results from CARTITUDE-1 are consistent with those seen in the LEGEND-2 study (with LCAR-B38M) conducted in a Chinese population, confirming the reliability of the chosen target dose of 0.75 × 106 CAR+ cells/kg.

In early December 2019, JNJ-4528 received breakthrough designation from the FDA, and the phase 2 portion of the study is now fully enrolled.

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Last modified: February 17, 2021

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