Carvykti (ciltacabtagene autoleucel) significantly improved progression-free survival and deepened responses versus two standard therapies for patients with functional high-risk multiple myeloma

The data show Carvykti (ciltacabtagene autoleucel; cilta-cel) significantly improved progression-free survival (PFS) compared to standard therapies of pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd) for patients with lenalidomide-refractory multiple myeloma after one prior line of therapy (LOT), including patients with functional high-risk (FHR) multiple myeloma. FHR was defined as progressive disease within 18 months after receiving autologous stem cell transplant (ASCT) or the start of initial frontline therapy in patients with no ASCT.

These data were featured as an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #7504) and will also be shared at the 2024 European Hematology Association (EHA) Congress (Abstract #P959).

Data from the CARTITUDE-4 study supported the recent FDA approval of Carvykti, the first and only B-cell maturation antigen (BCMA)-targeted therapy approved for the treatment of patients with relapsed/refractory multiple myeloma as early as after first relapse.

A Phase III CARTITUDE-4 subgroup analysis included 136 patients (Carvykti, n=68; standard therapies, n=68) who received one prior LOT, including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD), and were lenalidomide-refractory. After a median follow-up of 16 months (range, 0.1-27), median PFS was not reached (NR) (95 percent Confidence Interval [CI]; not estimable [NE]-NE) among patients who received Carvykti compared to 17 months (95 percent CI, 11-NE) for the control arm as a second-line treatment (hazard ratio [HR]=0.35 [95 percent CI, 0.2-0.7; P=.0007]).

In an additional subgroup analysis of 79 patients with FHR multiple myeloma (Carvykti, n=40; standard therapies, n=39) median PFS was NR [18-NE] with Carvykti versus 12 months (8-NE) with standard therapies (HR=0.27 [95 percent CI, 0.1-0.6; P=.0006]). Patients treated with Carvykti had deeper overall response rates (88 percent; 80 percent), complete response (CR) or better (68 percent; 39 percent), minimal residual disease (MRD) negativity (65 percent; ten percent), and longer median duration of response (mDOR) (NR [16-NE]; 16 [8-NE]) compared to those treated with standard therapies.

“Patients with functional high-risk myeloma whose disease progressed during the first 18 months of initial myeloma therapy are known to have poor prognosis, yet they have not been well represented in any clinical trial,” said Luciano J. Costa, M.D., Ph.D., Professor of Medicine and Director of the Multiple Myeloma Program, University of Alabama at Birmingham, and principal study investigator. “This subset analysis of CARTITUDE-4 provides strong evidence that these patients greatly benefit from cilta-cel and will help healthcare professionals better understand the potential of this therapy.”

The proportion of patients with grade 3 or higher treatment-emergent adverse events (TEAEs) was comparable among patients who received Carvykti versus standard therapies as second-line treatment (96 percent, 96 percent) and those with one prior LOT and FHR multiple myeloma (100 percent, 97 percent), respectively. Overall, 11 patients in the Carvykti one prior LOT subgroup and 11 patients in the standard therapies one prior LOT subgroup died. Of patients with FHR multiple myeloma, seven patients from the Carvykti arm and nine who received standard therapies died. Of the seven deaths in patients with one prior LOT and FHR multiple myeloma, two did not receive Carvykti as study treatment and three received Carvykti as subsequent therapy.

“Many patients with FHR multiple myeloma from the CARTITUDE-4 subgroup analysis experienced deep and durable responses following the single-infusion of Carvykti, further supporting the potential to treat a broader patient population,” said Jordan Schecter, M.D., Vice President, Disease Area Leader, Multiple Myeloma, at Johnson & Johnson Innovative Medicine. “At Johnson & Johnson, we aspire to eliminate cancer and remain steadfast in our commitment to realizing the full potential of Carvykti to improve outcomes for patients.”

CARTITUDE-2: Cilta-cel results in patients with suboptimal response to frontline autologous stem cell transplant ± lenalidomide maintenance (Abstract #7505) : Results from Cohort D of the CARTITUDE-2 study demonstrated deep and durable responses following a single infusion of cilta-cel with or without lenalidomide maintenance. This cohort evaluated patients who had a suboptimal response after ASCT frontline therapy. These data were presented as an oral presentation at the 2024 ASCO Annual Meeting (Abstract #7505). At a median follow-up of 22 months, patients treated with cilta-cel (n=17) demonstrated a 94 percent overall response rate, with 94 percent also achieving a CR or better. Of the 15 MRD-evaluable patients, 80 percent achieved MRD negativity at 10. The mDOR was NR. Eighteen-month PFS and OS rates were 94 percent each. Patients in Cohort D had robust CAR-T expansion, but numerically shorter persistence compared to patients with lenalidomide-refractory multiple myeloma and one to three prior LOT (CARTITUDE-4) and heavily pretreated patients (CARTITUDE-1).

All patients had grade 3 or 4 TEAEs including any grade neutropenia (94 percent), lymphopenia (65 percent), thrombocytopenia (47 percent), leukopenia (41 percent), infections (71 percent), or cytokine release syndrome (CRS) (82 percent; median onset of eight days), One patient had a secondary malignancy of grade 3 myelodysplastic syndromes (MDS). No cases of movement and neurocognit.ve treatment-emergent (MNT) AEs/parkinsonism were observed.

About CARTITUDE-4 :CARTITUDE-4 (NCT04181827) is the first international, randomized, open-label Phase III study evaluating the efficacy and safety of cilta-cel versus pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd) in adult patients with relapsed and lenalidomide-refractory multiple myeloma who received one to three prior lines of therapy. Results were presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting and published in The New England Journal of Medicine.

About CARTITUDE-2 :CARTITUDE-2 (NCT04133636) is an ongoing, multi-cohort Phase 2 study evaluating the safety and efficacy of cilta-cel in patients with multiple myeloma. Cohort D evaluates cilta-cel with lenalidomide maintenance in patients who achieved less than complete response (CR) after autologous stem cell transplant (ASCT) frontline therapy.

See- "Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma"-Authors: Jesús San-Miguel, M.D., Ph.D., Binod Dhakal, M.D., Kwee Yong, Ph.D., Andrew Spencer, M.D., Sébastien Anguille, M.D., Ph.D., María-Victoria Mateos, M.D., Ph.D., Carlos Fernández de Larrea, M.D., Ph.D., +35, and Hermann Einsele, M.D. Published June 5, 2023. N Engl J Med 2023;389:335-34DOI: 10.1056/NEJMoa2303379. VOL. 389 NO..

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