CARVYKTI®
(ciltacabtagene autoleucel)
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CARVYKTI® (ciltacabtagene autoleucel)
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CARVYKTI - CARTITUDE-2 (MMY2003) Cohort B - Use in Early Relapse Multiple Myeloma After Initial Therapy
Last Updated: 11/21/2025
SUMMARY
CARVYKTI is not approved by the regulatory agencies for use in early relapse multiple myeloma (MM). Janssen does not recommend the use of CARVYKTI in a manner that is inconsistent with the approved labeling. - CARTITUDE-2 is an ongoing, phase 2, multicohort, open-label study evaluating CARVYKTI in patients with MM in various clinical settings.
- Cohort B evaluates patients with early relapse (≤12 months after frontline therapy or ≤12 months after autologous stem cell transplant [ASCT]). One patient was treated in an outpatient setting to evaluate the suitability of outpatient administration of CARVYKTI.1
- 3 - Hillengass et al (2023)1 presented the updated efficacy and safety results from cohort B of the CARTITUDE-2 study at a median follow-up of 27.9 months.
- van de Donk et al (2021)2
presented the initial efficacy and safety results from cohort B of the CARTITUDE-2 study at a median follow-up of 10.6 months.
- Cohort B evaluates patients with early relapse (≤12 months after frontline therapy or ≤12 months after autologous stem cell transplant [ASCT]). One patient was treated in an outpatient setting to evaluate the suitability of outpatient administration of CARVYKTI.1
- Cohort B: 1 prior LOT, including a PI and an immunomodulatory drug; disease progression ≤12 months after ASCT or ≤12 months from other antimyeloma therapy. Suitability of outpatient administration for CARVYKTI is also being explored.
1-3 - Early relapse was defined as progression within 12 months after autologous stem cell transplant (ASCT) or from the start of anti-MM therapy for patients who did not undergo ASCT.
2
- Early relapse was defined as progression within 12 months after autologous stem cell transplant (ASCT) or from the start of anti-MM therapy for patients who did not undergo ASCT.
Study Design/Methods
- The study design is presented in Figure: CARTITUDE-2 (Cohort B) Study Design.
Abbreviations: ASCT, autologous stem cell transplant; ASTCT, American Society for Transplantation and Cellular Therapy; BCMA, B-cell maturation antigen; CAR, chimeric antigen receptor; CAR-T, chimeric antigen receptor-T cell; cilta-cel, ciltacabtagene autoleucel; CRS, cytokine release syndrome; Cy, cyclophosphamide; ECOG PS, Eastern Cooperative Oncology Group performance status; Flu, fludarabine; ICANS, immune effector cell-associated neurotoxicity syndrome; IMWG, International Myeloma Working Group; LOT, line of therapy; MRD, minimal residual disease; NCI-CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events; NGF, next-generation flow; NGS, next-generation sequencing; ORR, overall response rate; PD, pharmacodynamics; PI, proteasome inhibitor; PK, pharmacokinetics.
a
- Per protocol, bone marrow aspirate samples for minimal residual disease (MRD) evaluation were collected at the time of a suspected complete response (CR)/stringent complete response (sCR); at months 2, 6, 12, 18, and 24 for all dosed patients; and yearly thereafter for patients in CR/sCR.1
Results
Patient Demographics and Disease/Treatment Characteristics
Patient details are presented in Table: CARTITUDE-2 (Cohort B): Demographics and Disease Characteristics.
Efficacy
Efficacy outcomes at a median follow-up of 27.9 months (range, 5.2-32.1) are presented in Table: CARTITUDE-2 Cohort B: Efficacy - Response.
| Parameter | N=19 |
|---|---|
| ORR, % | 100 |
| sCR, % | 73.7 |
| CR, % | 15.8 |
| VGPR, % | 10.5 |
| PR, % | 0 |
| ≥CR, % | 89.5 |
| Evaluable patients for overall MRDa negativity, n | 15 |
| MRD negativity (10-5 | 93.3 (14) |
| Sustained MRD negativityb | |
| Evaluable patients for sustained MRD negativity for ≥6 monthsc | 13 |
| Sustained MRD negativity (10-5) ≥6 monthsd | 10 (76.9) |
| Evaluable patients for sustained MRD negativity for ≥12 monthse | 13 |
| Sustained MRD negativity (10-5) ≥12 monthsf | 8 (61.5) |
| MRD-negative CR/sCRg | 68.4 (13) |
| Median (range) time to first response, months | 0.95 (0.9-9.7) |
| Median (range) time to best response, months | 5.1 (0.9-11.8) |
| PFS rate at 24 months, % (95% CI) | 73.3 (47.2-87.9) |
| OS rate at 24 months, % (95% CI) | 84.2 (58.7-94.6) |
| 24-month DOR rate, % (95% CI) | 70.5 (42.5-86.7) |
| Abbreviations: CI, confidence interval; CR, complete response; DOR, duration of response; MRD, minimal residual disease; NGF, next-generation flow; NGS, next-generation sequencing; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PR, partial response; sCR, stringent complete response; VGPR, very good partial response. aPatients who were MRD evaluable had a clone identified and had at least 1 postbaseline MRD sample that included sufficient cells for evaluation at the 10-5 testing threshold (for NGS) or at least 1 postbaseline sample with a positive or negative result (for NGF). bPost hoc analysis. cPatients who achieved overall MRD negativity and had at least an evaluable MRD sample at the 10-5 testing threshold at or after 6 months after their first MRD negativity or experienced progression, started subsequent therapy, or died due to progressive disease within 6 months after their first MRD negativity. dMRD negativity confirmed at least 6 months apart without an MRD-positive result in between. Percentage is calculated with the number of patients evaluable for sustained MRD negativity ≥6 months as the denominator. ePatients who achieved overall MRD negativity and had at least an evaluable MRD sample at the 10-5 testing threshold at or after 12 months after their first MRD negativity or experienced progression, started subsequent therapy, or died due to progressive disease within 12 months after their first MRD negativity. fMRD negativity confirmed at least 12 months apart without an MRD-positive result in between. Percentage is calculated with the number of patients evaluable for sustained MRD negativity ≥12 months as the denominator. gOnly MRD assessments (10-5 testing threshold) within 3 months of achieving CR/sCR until death/progression/subsequent therapy (exclusive) are considered. | |
Safety
At the 27.9-month median follow-up, treatment-emergent adverse events (AEs) of any grade were reported in 100% of patients (n=19), with grade 3/4 events reported in 94.8% of patients (n=18). Serious treatment-emergent AEs of any grade were reported in 36.8% of patients (n=7). - Secondary primary malignancies were reported in 2 patients (grade 2 prostate cancer [n=1], not treatment related; grade 4 choroid melanoma [n=1], not treatment related).
A total of 4 deaths occurred due to progressive disease (n=3) and cardiac arrest (n=1; not treatment related). - The most common (all grade) hematologic AEs occurring in ≥20% of patients are noted in Table: CARTITUDE-2 (Cohort B): Hematologic Treatment-Emergent Adverse Events.
| Event, n (%) | N=19 | |
|---|---|---|
| Any Grade | Grade 3/4 | |
| Neutropenia | 18 (94.7) | 17 (89.5) |
| Anemia | 11 (57.9) | 9 (47.4) |
| Thrombocytopenia | 11 (57.9) | 5 (26.3) |
| Lymphopenia | 9 (47.4) | 9 (47.4) |
| Leukopenia | 6 (31.6) | 6 (31.6) |
- Cytokine release syndrome (CRS) of any grade occurred in 84.2% of patients (n=16). The incidence, timing/duration, and management of CRS are detailed in Table: CARTITUDE-2 (Cohort B): CRS. At data cutoff, all CRS cases had resolved.
| Total (N=19) | |
|---|---|
| Patients with a CRS event, n (%) | 16 (84.2) |
| Patients with a grade 3/4CRS event, n (%) | 1 (5.3) |
| Median time to onset of CRS, days | 8 |
| Median duration of CRS, days | 4 |
| Abbreviation: CRS, cytokine release syndrome. | |
Neurotoxicity
The incidence of neurotoxicity is detailed in Table: CARTITUDE-2 (Cohort B): Neurotoxicities. - One patient experienced grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS). The time to onset was 11 days, with a duration of 4 days. No patients experienced grade 3/4 ICANS. At data cutoff, all ICANS cases had resolved.
- Other neurotoxicities of any grade occurred in 5 patients (26.3%), comprising 1 case each of movement and neurocognitive treatment-related adverse event (MNT; not resolved), hypoesthesia (not resolved), sensory loss (resolved), facial paralysis (resolved), and personality change (resolved). The median time to onset of other neurotoxicities was 22 days, with a median duration of 128 days. Other neurotoxicity cases were resolved in 3/5 patients.
- One patient (male; age, 44 years) developed grade 3 MNT with a median time to onset of 38 days after CARVYKTI infusion.1,
2 - At data cutoff, the event was not recovered/resolved. The patient died due to cardiac arrest on day 749 after CARVYKTI infusion.
- At data cutoff, the event was not recovered/resolved. The patient died due to cardiac arrest on day 749 after CARVYKTI infusion.
| Total (N=19) | ||
|---|---|---|
| Any Grade | Grade 3/4 | |
| Neurotoxicity, n (%) | 6 (31.6) | 1 (5.3) |
| ICANSa, n (%) | 1 (5.3) | 0 |
| Other neurotoxicitiesb, n (%) | 5c (26.3) | 1 (5.3) |
| MNT | 1d (5.3) | 1 (5.3) |
| Abbreviations: CAR, chimeric antigen receptor; CRS, cytokine release syndrome; ICANS, immune effector cell-associated neurotoxicity syndrome; MNT, movement and neurocognitive treatment-related adverse event. aICANS was graded according to American Society for Transplantation and Cellular Therapy criteria. bOne new other neurotoxicity of grade 2 sensory loss (which resolved) since the last data cutoff. cOne case each of MNT (not resolved), hypoesthesia (not resolved), sensory loss (resolved), facial paralysis (resolved), and personality change (resolved). dPatient had associated risk factors for MNTs (high baseline tumor burden [95% plasma cells in bone marrow biopsy at lymphodepletion (M-protein level change from 5.0 g/dL at screening to 6.1 g/dL at lymphodepletion chemotherapy)], worsening burden despite bridging therapy, grade 4 CRS, and high CAR-T-cell expansion and persistence). | ||
Patient Demographics and Disease/Treatment Characteristics
Overall, 19 patients were lymphodepleted and treated with CARVYKTI in cohort B of the CARTITUDE-2 study. Patient details are presented in Table: CARTITU
| Total (N=19) | |
|---|---|
| Median age (range), years | 58 (44-67) |
| Male, n (%) | 14 (73.7) |
| Race, n (%) | |
| White | 14 (73.7) |
| Black/African American | 2 (10.5) |
| Asian | 1 (5.3) |
| Not reported | 2 (10.5) |
| Bone marrow plasma cells ≥60%a, n (%) | 4 (21.1) |
| Extramedullary plasmacytomas, n (%) | 3 (15.8) |
| High-risk cytogenetic profileb, n (%) | 3 (15.8)c |
| del17p | 3 (15.8) |
| Median years since diagnosis,(range) | 1.15 (0.5-1.9) |
| Median number of prior lines of therapy, (range) | 1 (1-1) |
| Prior stem cell transplantation, n (%) | |
| Autologous | 15 (78.9) |
| Allogeneic | 0 |
| Triple-class exposedd, n (%) | 4 (21.1) |
| Penta-drug exposede, n (%) | 0 |
| Refractory status, n (%) | |
| Lenalidomide | 15 (78.9) |
| Bortezomib | 6 (31.6) |
| Daratumumab | 3 (15.8) |
| Thalidomide | 2 (10.5) |
| Triple-class refractoryd | 3 (15.8) |
| Penta-drug refractorye | 0 |
| Refractory to last line of therapy | 15 (78.9) |
| Abbreviation: CD, cluster of differentiation. aMaximum value from bone marrow biopsy and bone marrow aspirate is selected if both results are available. bAny of the following 4 abnormal cytogenetic features: del17p, t(4;14), t(14;16), or 1q. cThree patients had unknown cytogenetics. dAt least 1 proteasome inhibitor, at least 1 immunomodulatory drug, and 1 anti-CD38 antibody. e≥2 proteasome inhibitors, ≥2 immunomodulatory drugs, and 1 anti-CD38 antibody. | |
Efficacy
- Efficacy outcomes at a median follow-up of 10.6 months (range, 4.1-17.4) are presented in Table: CARTITUDE-2 Cohort B: Efficacy - Response.
| Parameter | N=19 |
|---|---|
| ORRa, % (95% CI) | 95 (74.0-99.9) |
| sCR, % | 53 |
| CR, % | 26 |
| VGPR, % | 11 |
| PR, % | 5 |
| ≥CR, % (95% CI) | 79 (54.4-93.9) |
| ≥VGPR, % (95% CI) | 90 (66.9-98.7) |
| Evaluable patients for MRDa negativity at 10-5 threshold, n | 13 |
| MRD negativity among MRD-evaluable patientsa at data cutoff, % (95% CI), | 92.3 (64.0-99.8) |
| Median time to first response (range), months | 1 (0.9-2.6) |
| Median time to best response (range), months | 2.5 (0.9-11.8) |
| PFS rate at 6 months, % (95% CI) | 90 (64.1-97.3) |
| PFS rate at 12 months, % (95% CI) | 84 (57.9-94.5) |
| Median DOR (95% CI), months | NR |
| Abbreviations: CI, confidence interval; CR, complete response; DOR, duration of response; MRD, minimal residual disease; NR, not reached; ORR, overall response rate; PFS, progression-free survival; PR, partial response; sCR, stringent complete response; VGPR, very good partial response. aOne patient had stable disease. | |
Safety
- At a median follow-up of 10.6 months, the most common AEs (≥20%; any grade) were as follows: headache (32%), pyrexia (32%), asthenia (26%), back pain (21%), and myalgia (21%).
- The patient who was administered CARVYKTI in an outpatient setting had a manageable safety profile.
- The most common (all grade) hematologic AEs are noted in Table: CARTITUDE-2 (Cohort B): Hematologic Treatment-Emergent Adverse Events.
| Event, n (%) | N=19 | |
|---|---|---|
| Any Grade | Grade 3/4 | |
| Neutropenia | 17 (90) | 16 (84) |
| Anemia | 11 (58) | 9 (47) |
| Thrombocytopenia | 11 (58) | 5 (26) |
| Lymphopenia | 6 (32) | 6 (32) |
| Leukopenia | 5 (26) | 5 (26) |
Cytokine Release Syndrome
- The incidence, timing/duration, and management of CRS are detailed in Table: CARTITUDE-2 (Cohort B): CRS.
| Total (N=19) | |
|---|---|
| Patients with a CRS eventa, n (%) | 16 (84) |
| Patients with a grade 4 CRS event a, n (%) | 1 (5) |
| Median time to onset of CRS (range), days | 8 (5-11) |
| Median duration of CRS (range), days | 3.5 (1-7) |
| Supportive measuresb, n (%) | |
| Tocilizumab | 12 (63) |
| Anti-infectives | 9 (47) |
| Analgesics/anti-inflammatory agents | 9 (47) |
| Corticosteroids | 4 (21) |
| Oxygen | 1 (5) |
| Vasopressors | 1 (5) |
| Other | 1 (5) |
| Abbreviation: CRS, cytokine release syndrome. aCRS was graded according to American Society for Transplantation and Cellular Therapy criteria. bInclude supportive measures to treat CRS events and symptoms. | |
Neurotoxicity
- The incidence of neurotoxicity is detailed in Table: CARTITUDE-2 (Cohort B): Neurotoxicities.
- One patient experienced grade 1 ICANS. The time to onset was 11 days, with a duration of 4 days.
- One patient (male; age, 44 years) developed grade 3 MNTs, with a median time to onset of 38 days after CARVYKTI infusion.
- The patient had associated risk factors for MNTs (high baseline tumor burden worsening despite bridging therapy, grade 4 CRS, and high CAR-T-cell expansion and persistence).
- At data cutoff, the patient was reported to be stable with some improvements and had achieved CR to CARVYKTI.
| Total (N=19) | ||
|---|---|---|
| Any Grade | Grade 3/4 | |
| Neurotoxicity, n (%) | 5 (26) | 1 (5) |
| ICANSa, n (%) | 1 (5) | 0 |
| Other neurotoxicities, n (%) | 4 (21) | 1 (5) |
| MNT | 1 (5) | 1 (5) |
| Abbreviations: ICANS, immune effector cell-associated neurotoxicity syndrome; MNT, movement and neurocognitive treatment-related adverse event. aICANS was graded according to American Society for Transplantation and Cellular Therapy criteria. | ||
Literature Search
A literature search of MEDLINE®
References
| 1 | Hillengass J, Cohen AD, Agha M, et al. The phase 2 CARTITUDE-2 trial: updated efficacy and safety of ciltacabtagene autoleucel in patients with multiple myeloma and 1–3 prior lines of therapy (cohort A) and with early relapse after first line treatment (cohort B). Oral Presentation presented at: 65th American Society of Hematology (ASH) Annual Meeting and Exposition; December 9-12, 2023; San Diego, CA. |
| 2 | |
| 3 |