During a Case-Based Roundtable® event, Samer A. Al'Hadidi, MD, MS, discussed the CARTITUDE-4 trial of cilta-cel in patients with relapsed/refractory multiple myeloma in the first article of a 2-part series.
CASE SUMMARY
Targeted Oncology: Please discuss the trial behind the treatment selection for this patient.
Samer A. Al'Hadidi, MD, MS: This is a very important study that we should look at in detail. CARTITUDE-4 [NCT04181827] is a phase 3 study, which is a very important because with CAR T-cell therapy, we worry about selecting patients with good biology to give the CAR T cells, so a phase 3 trial was something all of us were waiting to see. This is a study [that enrolled] patients with relapsed disease after 1 to 3 lines of therapy. One requirement was being refractory to lenalidomide, which is almost universal in the United States. Patients were randomly assigned to 1 of 2 triplet regimens vs cilta-cel: either pomalidomide [Pomalyst], bortezomib, dexamethasone or daratumumab, pomalidomide, dexamethasone. These are 2 commonly used regimens for patients who were not anti-CD38 exposed, so something that many of us use.1
This study’s primary end point was progression-free survival [PFS].... The randomization was 1:1 [between CAR T-cell therapy and triplet therapy]. The characteristics of the patients who were enrolled in this study showed most patients got between 1 to 3 lines of previous therapy. One hundred percent of patients were on lenalidomide before, and a minority of patients were on daratumumab. So it's a little bit different than our case, where the patient had daratumumab. It's probably the minority here, under 25%. [Around one-third of patients] received bortezomib before, and around one-third got carfilzomib [Kyprolis]. So those patients were not heavily pretreated. All those patients were refractory to lenalidomide [and to] a proteasome inhibitor, [including about 97% with] bortezomib and one-fourth with carfilzomib. But when it comes to anti-CD38, only 1/4 of those patients were refractory.
This is similar to the patient case that we have, where the patient had only 1 line of treatment, and was not heavily pretreated.
What was the efficacy seen on the CARTITUDE-4 study for patients with early relapsed/refractory multiple myeloma?
The Kaplan-Meier curve for PFS showed cilta-cel had better PFS, and the standard of care had worse PFS. There was, early in the study, some crossover where patients went to the cilta-cel group who did have progression events and mortality-related events before getting the CAR T-cell therapy. Looking into the intention-to-treat analysis in this study, the cilta-cel median PFS was not reached, and the standard of care PFS was [a median of] 11.8 months, which is standard on pomalidomide-based regimens. Most pomalidomide-based regimens after 1 to 3 lines of treatments give you around a year of PFS, so that is the usual that we see. But the HR between those was low at 0.26 [95% CI, 0.18-0.38], so those were really good results.
The CR or better and overall response were better, and those responses are really deeper. Almost three-fourths of patients go to CR compared with only around 22% of patients [with triplet]. This was with a median follow-up of around 16 months and in the future, we will get more follow-up on this important study. But even with that, we can see there was improvement on the PFS.
With patients following up for a longer period of time, the responses were becoming deeper.2 The overall responses were better with time at 16-month follow-up, but also [the rate of] VGPR or better is [higher], along with CR or better [86%]. The time to first response after randomization was around 2 months on this cohort, and most patients were progression free at 1 year after getting cilta-cel. That PFS rate was almost 85% and the overall survival rate was high at around 92%. Those responses are really deep, with many of them achieving a minimum residual disease negativity in almost three-fourths. So there were deeper responses, and also that build up with time, which is nice to see.
Functional High Risk and Bridging in Multiple Myeloma Considered With CAR T Cells
October 9th 2024Samer A. Al'Hadidi, MD, MS, reviewed the benefits of cilta-cel in the subgroup analysis of CARTITUDE-4 in patients with relapsed/refractory multiple myeloma and functional high risk, bridging to cilta-cel, and time to treatment in the second article of a 2-part series.
Read More
Lenalidomide Break Possible? Study Shows Hope for MRD-Negative Myeloma
October 7th 2024A new study suggests that patients with multiple myeloma who achieve sustained MRD-negativity for at least three years may be able to discontinue maintenance therapy without compromising their long-term outcomes.
Read More
DREAMM-8 Trial Demonstrates Benefits of Belantamab Mafodotin
October 3rd 2024Belantamab mafodotin plus pomalidomide and dexamethasone showed significant progression-free survival benefits and maintained quality of life in patients with relapsed/refractory multiple myeloma, as demonstrated in the DREAMM-8 trial.
Read More