Efficacy of Cilta-Cel Is Maintained in Early Relapsed Multiple Myeloma

Samer A. Al'Hadidi, MD, MS

Hematologist/Oncologist

Assistant Professor of Medicine

University of Arkansas for Medical Sciences

Little Rock, AR

CASE SUMMARY

• A 60-year-old man who was diagnosed 3 years ago with lenalidomide refractory IgG-kappa multiple myeloma presented to his oncologist at first relapse with 1 prior treatment. Patient stated complaints of excessive fatigue and low back pain exacerbated by movement.
• Lived in a rural community.
• Medical history: hypertension controlled with lisinopril
• He received previous treatments with:
• Dara-VRd (daratumumab [Darzalex], bortezomib [Velcade], lenalidomide [Revlimid], dexamethasone) followed by autologous stem cell transplant (ASCT) with lenalidomide maintenance
• Achieved very good partial response (VGPR) post-ASCT
• ECOG performance status: 0
• Weighed 170 lbs (down 15 lbs in last 4 months)
• After discussion with his oncology team, the patient began evaluations for chimeric antigen receptor (CAR) T-cell referral.
• The patient ultimately proceeded to ciltacabtagene autoleucel (cilta-cel; Carvykti) CAR T-cell infusion.
• Achieved stringent complete response (CR) at day 30.

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.

_References:

_{1. San-Miguel J, Dhakal B, Yong K, et al. Cilta-cel or standard care in lenalidomide-refractory multiple myeloma. N Engl J Med. 2023;389(4):335-347. doi:10.1056/NEJMoa2303379}

_{2. Sidiqi MH, Corradini P, Purtill D, et al. Efficacy and safety in patients with lenalidomide-refractory multiple myeloma after 1-3 prior lines who received a single infusion of ciltacabtagene autoleucel as study treatment in the phase 3 CARTITUDE-4 trial. Blood. 2023;142(suppl 1):4866. doi:10.1182/blood-2023-178778}