SUMMARY

• CARTITUDE-1 (MMY2001) was a phase 1b/2, open-label, single-arm, multicenter study evaluating ciltacabtagene autoleucel (cilta-cel) in patients with relapsed/refractory multiple myeloma (RRMM) who had previous received a proteasome inhibitor (PI), an immunomodulatory agent, and an anti-CD38 antibody. The combined analysis from the phase 1b/2 portions of the CARTITUDE-1 study evaluated the safety and efficacy of cilta-cel in 97 patients with RRMM.^1-4
• CARTITUDE-4 (MMY3002) is a phase 3, randomized, open-label study evaluating the efficacy and safety of cilta-cel versus standard care (physician's choice of pomalidomide, bortezomib, and dexamethasone [PVd] or DARZALEX FASPRO^® [daratumumab and hyaluronidase], pomalidomide, and dexamethasone [DPd]) in adult patients with lenalidomide-refractory multiple myeloma (MM) after 1-3 prior line(s) of therapy (LOT).^5,6
• The permitted medications in CARTITUDE-1 and CARTITUDE-4 are summarized below.

PRODUCT LABELING

• CARVYKTI (ciltacabtagene autoleucel) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.;  https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/CARVYKTI-pi.pdf.
• DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX+Faspro-pi.pdf.

Clinical data - CARTITUDE-1 - PHASE 1B/2 STUDY

CARTITUDE-1 (MMY2001; clinicaltrials.gov identifier: NCT03548207) was a phase 1b/2, open-label, single-arm, multicenter study that evaluated the safety and efficacy of cilta-cel in patients with RRMM who had previously received a PI, an immunomodulatory agent, and an antiCD38 antibody. The combined analysis from the phase 1b/2 portions of the CARTITUDE-1 study evaluated the safety and efficacy of cilta-cel in 97 patients with RRMM.^1-4

Study Design/Methods

• Anti-myeloma therapy (medications which the patient has previously received) was permitted during bridging therapy.²
  • Bridging therapy (anti-plasma cell directed treatment between apheresis and the first dose of the conditioning/lymphodepletion regimen) was allowed when clinically indicated (ie, to maintain disease stability while waiting for manufacturing of
    cilta-cel). Additional cycles of bridging therapy may be considered based on patient’s clinical status and timing of availability of cilta-cel.²
  • Bridging therapy as originally defined allowed for short-term treatment with previously used agent resulting in at least stable disease. Patients were not permitted to receive cilta-cel infusion if they had complete response after bridging therapy.²

CARTITUDE-1 Study Protocol - Permitted Medications

The following are examples of supportive therapies that may have been used during the study²:

• Standard supportive care therapies (antiemetics, antidiarrheals, anticholinergics, antispasmodics, antipyretics, antihistamines, analgesics, antibiotics and other antimicrobials, histamine receptor [H₂] antagonists or proton pump inhibitors, and other medications intended to treat symptoms or signs of disease) and therapies intended to treat chimeric antigen receptor-T (CAR-T) cell-related toxicity (ie, cytokine release syndrome [CRS]) as clinically indicated, according to institutional standards and as deemed necessary by the investigator.²
• Bisphosphonates may be initiated (if not already being administered) unless contraindicated within 1 week prior to the first dose of study treatment and continued until disease progression is established. In the case of severe adverse events such as hypercalcemia, bisphosphonates may be administrated as clinically indicated, according to institutional standards and as deemed necessary by the investigator.²
• Hematopoietic growth factor support and transfusions (irradiated blood products) are permitted to treat symptoms or signs of neutropenia, anemia or thrombocytopenia according to local standards of care. Non-pegylated myeloid growth factors are permitted up to 1 day prior to the start of the conditioning/lymphodepletion regimen (cyclophosphamide and fludarabine).²
• Documented infectious complications should be treated with oral or intravenous (IV) antibiotics or other anti-infective agents as considered appropriate by the treating investigator, according to standard institutional practice.²
• Chemotherapy agents used to treat CAR-T cell-related toxicities are permitted upon consultation with the sponsor.²

Clinical data - CARTITUDE-4 - Phase 3 study

CARTITUDE-4 (MMY3002; clinicaltrials.gov identifier: NCT04181827) is an ongoing, phase 3, randomized, open-label study evaluating the efficacy and safety of cilta-cel versus standard care (physician's choice of PVd or DPd) in adult patients with lenalidomide-refractory MM after 1-3 prior LOT.^5,6

Study Design/Methods

• Supportive measures were permitted for patients meeting criteria to proceed with cyclophosphamide and fludarabine dosing⁷:
  • Transfusion support was permitted to maintain a hemoglobin of ≥8 g/dL as needed, and platelets of ≥50 x 10⁹/L until 3 days before the hematology laboratory test, preceding lymphodepletion.
  • Myeloid growth factors were permitted at investigator’s discretion up to 1 day prior to the start of the conditioning regimen.

CARTITUDE-4 Study Protocol - Permitted Medications

The following are examples of supportive therapies that may be used during the study for patients randomized to either the standard care arm or cilta-cel arm⁷:

• Standard supportive care therapies (antiemetics, antidiarrheals, anticholinergics, antispasmodics, antipyretics, antihistamines, analgesics, antibiotics and other antimicrobials, H₂ antagonists or proton pump inhibitors, and other medications intended to treat symptoms or signs of disease) and therapies intended to treat CAR-T cell related toxicity (ie, CRS) as clinically indicated, according to institutional standards and as deemed necessary by the investigator.⁷
• Bisphosphonates may be administered as clinically indicated, according to institutional standards. The sponsor must be notified promptly in cases where bisphosphonates are given for the management of hypercalcemia.⁷
• Hematopoietic growth factor support and transfusions (irradiated blood products) are permitted to treat symptoms or signs of neutropenia, anemia, or thrombocytopenia according to local standards of care. Non-pegylated myeloid growth factors are permitted up to 1 day prior to the start of the conditioning regimen including cyclophosphamide and fludarabine (cilta-cel arm only).⁷
• Documented infectious complications should be treated with oral or IV antibiotics or other anti-infective agents as considered appropriate by the treating investigator, according to standard institutional practice.⁷
• Chemotherapy agents used to treat CAR-T cell related toxicity are permitted upon consultation with the sponsor.⁷

Literature Search

A literature search of Ovid MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File databases (and/or other resources, including internal/external databases) was conducted on 11 March 2024.