ASCO: The Outstanding Results of Cilta-Cel in the CARTITUDE-4 Study

It's not every day that you get to sit in a session at a major academic meeting where the data is presented for a multiple myeloma clinical trial that you participated in.

That's where I found myself at ASCO in Chicago the first week of June, as the results were presented from the CARTITUDE-4 study, a clinical trial that tested the cilta-cel CAR T in patients with earlier relapses.  

About the CARTITUDE-4 Study

The study aimed to test cilta-cel, a CAR T product from Janssen Oncology and Legend Bio, in patients with fewer relapses with the hope that using it earlier would provide longer lasting effects. Cilta-cel (also known as Carvykti) is now FDA-approved for patients with at least 4 prior lines of therapy. 

In the study, 419 patients who had 1-3 prior lines of therapy (that included a proteasome inhibitor and immunomodulator) and who were refractory to lenalidomide were randomized with 50% of patients included in the CAR T arm and the other 50% of patients receiving either daratumumab/pomalidomide/dex (DPd) or pomalidomide/bortezomib/dex (PVd), based on the physician's choice. Patients could not have received a prior CAR T or BCMA-targeted therapy. 

Bridging therapy of DPd or PVd were used. The study goal was to analyze the progression free survival (PFS) of the patients, or how long until they relapsed. The mean follow-up for the study data was 15.9 months. 

Study Results

In the study, the cilta-cel group had a stunning 99% overall response rate and 86% of patients had a complete response (CR) or better. The majority of the patients (72%) became MRD negative, meaning that no disease could be deteced at the most sensitive levels. 

Comparing the study results to a prior study that included patients with more 4 or more lines of therapy (CARTITUDE-1), this study showed cilta-cel to be more effective when used in earlier lines of therapy. 

Overall, cilta-cel when used in earlier lines of therapy significantly extended progression free survival compared to "standard of care" triplet combinations.

Importantly, the benefits were seen across all subgroups:

• High risk genetics
• Extramedullary disease (or soft-tissue myeloma masses)
• ISS stage III disease
• Patients already exposed to daratumumab/isatuximab and proteasome inhibitors 

Side Effects

As the chart below indicates, patients experienced the side effects commonly found in CAR T therapy. Side effects are graded by severity with grade 3 or 4 being more severe. 

• 85-90% of patients had grade 3/4 neutropenia, or low blood counts
• Grade 3/4 infections were similar between the two study arms
• Secondary cancers were found in 4.3% of cilta-cel patients and 6.7% in the triplet combinations
• Deaths due side effects were found in 10 cilta-cel patients (7 due to COVID-19) and 5 in the triplet combinations (1 due to COVID-19)

Conclusions

The speaker concluded by noting: 

• Cilta-cel had powerful responses with a mangeable safety profile
• Although infections are common in immunotherapy treatments for myeloma, those infections were anticipated and highly treatable
• There were less significant infections in this study vs. the CARTITUDE-1 study, indicating that patients with fewer lines of treatment may have less severe side effects
• The progression free survival was seen in all sub-groups, including high-risk patients who are typically difficult to treat

This study was the talk of ASCO and suggests that the cilta-cel CAR T therapy could become a new standard of care treatment for patients who have relapsed after lenalidomide, as early as the first relapse.  It was exciting to see the data and to know that as a myeloma patient, I helped advance myeloma research through my participation.