Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma

Jesús San-Miguel; Binod Dhakal; Kwee Yong; Andrew Spencer; Sébastien Anguille; María Victoria Mateos; Carlos Fernández De Larrea; Joaquín Martínez-López; Philippe Moreau; Cyrille Touzeau; Xavier Leleu; Irit Avivi; Michele Cavo; Tadao Ishida; Seok Jin Kim; Wilfried Roeloffzen; Niels W.C.J. Van De Donk; Dominik Dytfeld; Surbhi Sidana; Luciano J. Costa; Albert Oriol; Rakesh Popat; Abdullah M. Khan; Yaël C. Cohen; P. Joy Ho; James Griffin; Nikoletta Lendvai; Carolina Lonardi; Ana Slaughter; Jordan M. Schecter; Carolyn C. Jackson; Kaitlyn Connors; Katherine Li; Enrique Zudaire; Diana Chen; Jane Gilbert; Tzu Min Yeh; Sarah Nagle; Erika Florendo; Lida Pacaud; Nitin Patel; Simon J. Harrison; Hermann Einsele

doi:10.1056/NEJMoa2303379

Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma

Jesús San-Miguel^*, Binod Dhakal, Kwee Yong, Andrew Spencer, Sébastien Anguille, María Victoria Mateos, Carlos Fernández De Larrea, Joaquín Martínez-López, Philippe Moreau, Cyrille Touzeau, Xavier Leleu, Irit Avivi, Michele Cavo, Tadao Ishida, Seok Jin Kim, Wilfried Roeloffzen, Niels W.C.J. Van De Donk, Dominik Dytfeld, Surbhi Sidana, Luciano J. CostaAlbert Oriol, Rakesh Popat, Abdullah M. Khan, Yaël C. Cohen, P. Joy Ho, James Griffin, Nikoletta Lendvai, Carolina Lonardi, Ana Slaughter, Jordan M. Schecter, Carolyn C. Jackson, Kaitlyn Connors, Katherine Li, Enrique Zudaire, Diana Chen, Jane Gilbert, Tzu Min Yeh, Sarah Nagle, Erika Florendo, Lida Pacaud, Nitin Patel, Simon J. Harrison, Hermann Einsele

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Background: Ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen (BCMA)-directed CAR T-cell therapy, is effective in heavily pretreated patients with relapsed or refractory multiple myeloma. We investigated cilta-cel in earlier treatment lines in patients with lenalidomide-refractory disease.

Methods: In this phase 3, randomized, open-label trial, we assigned patients with lenalidomide-refractory multiple myeloma to receive cilta-cel or the physician's choice of effective standard care. All the patients had received one to three previous lines of treatment. The primary outcome was progression-free survival.

Results: A total of 419 patients underwent randomization (208 to receive cilta-cel and 211 to receive standard care). At a median follow-up of 15.9 months (range, 0.1 to 27.3), the median progression-free survival was not reached in the cilta-cel group and was 11.8 months in the standard-care group (hazard ratio, 0.26; 95% confidence interval [CI], 0.18 to 0.38; P<0.001). Progression-free survival at 12 months was 75.9% (95% CI, 69.4 to 81.1) in the cilta-cel group and 48.6% (95% CI, 41.5 to 55.3) in the standard-care group. More patients in the cilta-cel group than in the standard-care group had an overall response (84.6% vs. 67.3%), a complete response or better (73.1% vs. 21.8%), and an absence of minimal residual disease (60.6% vs. 15.6%). Death from any cause was reported in 39 patients and 46 patients, respectively (hazard ratio, 0.78; 95% CI, 0.5 to 1.2). Most patients reported grade 3 or 4 adverse events during treatment. Among the 176 patients who received cilta-cel in the as-treated population, 134 (76.1%) had cytokine release syndrome (grade 3 or 4, 1.1%; no grade 5), 8 (4.5%) had immune effector cell-associated neurotoxicity syndrome (all grade 1 or 2), 1 had movement and neurocognitive symptoms (grade 1), 16 (9.1%) had cranial nerve palsy (grade 2, 8.0%; grade 3, 1.1%), and 5 (2.8%) had CAR-T-related peripheral neuropathy (grade 1 or 2, 2.3%; grade 3, 0.6%).

Conclusions: A single cilta-cel infusion resulted in a lower risk of disease progression or death than standard care in lenalidomide-refractory patients with multiple myeloma who had received one to three previous therapies. (Funded by Janssen and Legend Biotech; CARTITUDE-4 ClinicalTrials.gov number, NCT04181827.)

Original language	English
Pages (from-to)	335-347
Number of pages	13
Journal	New England Journal of Medicine
Volume	389
Issue number	4
DOIs	https://doi.org/10.1056/NEJMoa2303379
Publication status	Published - 27-Jul-2023

Keywords

Hematology/Oncology
Leukemia/Lymphoma
Treatments in Oncology

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Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple MyelomaFinal publisher's version, 625 KBLicence: Taverne

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San-Miguel, J., Dhakal, B., Yong, K., Spencer, A., Anguille, S., Mateos, M. V., Fernández De Larrea, C., Martínez-López, J., Moreau, P., Touzeau, C., Leleu, X., Avivi, I., Cavo, M., Ishida, T., Kim, S. J., Roeloffzen, W., Van De Donk, N. W. C. J., Dytfeld, D., Sidana, S., ... Einsele, H. (2023). Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma. New England Journal of Medicine, 389(4), 335-347. https://doi.org/10.1056/NEJMoa2303379

@article{0d46dcc237a74ab49506a6c2079d9334,

title = "Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma",

abstract = "Background: Ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen (BCMA)-directed CAR T-cell therapy, is effective in heavily pretreated patients with relapsed or refractory multiple myeloma. We investigated cilta-cel in earlier treatment lines in patients with lenalidomide-refractory disease.Methods: In this phase 3, randomized, open-label trial, we assigned patients with lenalidomide-refractory multiple myeloma to receive cilta-cel or the physician's choice of effective standard care. All the patients had received one to three previous lines of treatment. The primary outcome was progression-free survival.Results: A total of 419 patients underwent randomization (208 to receive cilta-cel and 211 to receive standard care). At a median follow-up of 15.9 months (range, 0.1 to 27.3), the median progression-free survival was not reached in the cilta-cel group and was 11.8 months in the standard-care group (hazard ratio, 0.26; 95% confidence interval [CI], 0.18 to 0.38; P<0.001). Progression-free survival at 12 months was 75.9% (95% CI, 69.4 to 81.1) in the cilta-cel group and 48.6% (95% CI, 41.5 to 55.3) in the standard-care group. More patients in the cilta-cel group than in the standard-care group had an overall response (84.6% vs. 67.3%), a complete response or better (73.1% vs. 21.8%), and an absence of minimal residual disease (60.6% vs. 15.6%). Death from any cause was reported in 39 patients and 46 patients, respectively (hazard ratio, 0.78; 95% CI, 0.5 to 1.2). Most patients reported grade 3 or 4 adverse events during treatment. Among the 176 patients who received cilta-cel in the as-treated population, 134 (76.1%) had cytokine release syndrome (grade 3 or 4, 1.1%; no grade 5), 8 (4.5%) had immune effector cell-associated neurotoxicity syndrome (all grade 1 or 2), 1 had movement and neurocognitive symptoms (grade 1), 16 (9.1%) had cranial nerve palsy (grade 2, 8.0%; grade 3, 1.1%), and 5 (2.8%) had CAR-T-related peripheral neuropathy (grade 1 or 2, 2.3%; grade 3, 0.6%).Conclusions: A single cilta-cel infusion resulted in a lower risk of disease progression or death than standard care in lenalidomide-refractory patients with multiple myeloma who had received one to three previous therapies. (Funded by Janssen and Legend Biotech; CARTITUDE-4 ClinicalTrials.gov number, NCT04181827.)",

keywords = "Hematology/Oncology, Leukemia/Lymphoma, Treatments in Oncology",

author = "Jes{\'u}s San-Miguel and Binod Dhakal and Kwee Yong and Andrew Spencer and S{\'e}bastien Anguille and Mateos, {Mar{\'i}a Victoria} and {Fern{\'a}ndez De Larrea}, Carlos and Joaqu{\'i}n Mart{\'i}nez-L{\'o}pez and Philippe Moreau and Cyrille Touzeau and Xavier Leleu and Irit Avivi and Michele Cavo and Tadao Ishida and Kim, {Seok Jin} and Wilfried Roeloffzen and {Van De Donk}, {Niels W.C.J.} and Dominik Dytfeld and Surbhi Sidana and Costa, {Luciano J.} and Albert Oriol and Rakesh Popat and Khan, {Abdullah M.} and Cohen, {Ya{\"e}l C.} and Ho, {P. Joy} and James Griffin and Nikoletta Lendvai and Carolina Lonardi and Ana Slaughter and Schecter, {Jordan M.} and Jackson, {Carolyn C.} and Kaitlyn Connors and Katherine Li and Enrique Zudaire and Diana Chen and Jane Gilbert and Yeh, {Tzu Min} and Sarah Nagle and Erika Florendo and Lida Pacaud and Nitin Patel and Harrison, {Simon J.} and Hermann Einsele",

note = "Publisher Copyright: {\textcopyright} 2023 Massachusetts Medical Society.",

year = "2023",

month = jul,

day = "27",

doi = "10.1056/NEJMoa2303379",

language = "English",

volume = "389",

pages = "335--347",

journal = "New England Journal of Medicine",

issn = "0028-4793",

publisher = "MASSACHUSETTS MEDICAL SOC",

number = "4",

}

San-Miguel, J, Dhakal, B, Yong, K, Spencer, A, Anguille, S, Mateos, MV, Fernández De Larrea, C, Martínez-López, J, Moreau, P, Touzeau, C, Leleu, X, Avivi, I, Cavo, M, Ishida, T, Kim, SJ, Roeloffzen, W, Van De Donk, NWCJ, Dytfeld, D, Sidana, S, Costa, LJ, Oriol, A, Popat, R, Khan, AM, Cohen, YC, Ho, PJ, Griffin, J, Lendvai, N, Lonardi, C, Slaughter, A, Schecter, JM, Jackson, CC, Connors, K, Li, K, Zudaire, E, Chen, D, Gilbert, J, Yeh, TM, Nagle, S, Florendo, E, Pacaud, L, Patel, N, Harrison, SJ & Einsele, H 2023, 'Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma', New England Journal of Medicine, vol. 389, no. 4, pp. 335-347. https://doi.org/10.1056/NEJMoa2303379

TY - JOUR

T1 - Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma

AU - San-Miguel, Jesús

AU - Dhakal, Binod

AU - Yong, Kwee

AU - Spencer, Andrew

AU - Anguille, Sébastien

AU - Mateos, María Victoria

AU - Fernández De Larrea, Carlos

AU - Martínez-López, Joaquín

AU - Moreau, Philippe

AU - Touzeau, Cyrille

AU - Leleu, Xavier

AU - Avivi, Irit

AU - Cavo, Michele

AU - Ishida, Tadao

AU - Kim, Seok Jin

AU - Roeloffzen, Wilfried

AU - Van De Donk, Niels W.C.J.

AU - Dytfeld, Dominik

AU - Sidana, Surbhi

AU - Costa, Luciano J.

AU - Oriol, Albert

AU - Popat, Rakesh

AU - Khan, Abdullah M.

AU - Cohen, Yaël C.

AU - Ho, P. Joy

AU - Griffin, James

AU - Lendvai, Nikoletta

AU - Lonardi, Carolina

AU - Slaughter, Ana

AU - Schecter, Jordan M.

AU - Jackson, Carolyn C.

AU - Connors, Kaitlyn

AU - Li, Katherine

AU - Zudaire, Enrique

AU - Chen, Diana

AU - Gilbert, Jane

AU - Yeh, Tzu Min

AU - Nagle, Sarah

AU - Florendo, Erika

AU - Pacaud, Lida

AU - Patel, Nitin

AU - Harrison, Simon J.

AU - Einsele, Hermann

PY - 2023/7/27

Y1 - 2023/7/27

N2 - Background: Ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen (BCMA)-directed CAR T-cell therapy, is effective in heavily pretreated patients with relapsed or refractory multiple myeloma. We investigated cilta-cel in earlier treatment lines in patients with lenalidomide-refractory disease.Methods: In this phase 3, randomized, open-label trial, we assigned patients with lenalidomide-refractory multiple myeloma to receive cilta-cel or the physician's choice of effective standard care. All the patients had received one to three previous lines of treatment. The primary outcome was progression-free survival.Results: A total of 419 patients underwent randomization (208 to receive cilta-cel and 211 to receive standard care). At a median follow-up of 15.9 months (range, 0.1 to 27.3), the median progression-free survival was not reached in the cilta-cel group and was 11.8 months in the standard-care group (hazard ratio, 0.26; 95% confidence interval [CI], 0.18 to 0.38; P<0.001). Progression-free survival at 12 months was 75.9% (95% CI, 69.4 to 81.1) in the cilta-cel group and 48.6% (95% CI, 41.5 to 55.3) in the standard-care group. More patients in the cilta-cel group than in the standard-care group had an overall response (84.6% vs. 67.3%), a complete response or better (73.1% vs. 21.8%), and an absence of minimal residual disease (60.6% vs. 15.6%). Death from any cause was reported in 39 patients and 46 patients, respectively (hazard ratio, 0.78; 95% CI, 0.5 to 1.2). Most patients reported grade 3 or 4 adverse events during treatment. Among the 176 patients who received cilta-cel in the as-treated population, 134 (76.1%) had cytokine release syndrome (grade 3 or 4, 1.1%; no grade 5), 8 (4.5%) had immune effector cell-associated neurotoxicity syndrome (all grade 1 or 2), 1 had movement and neurocognitive symptoms (grade 1), 16 (9.1%) had cranial nerve palsy (grade 2, 8.0%; grade 3, 1.1%), and 5 (2.8%) had CAR-T-related peripheral neuropathy (grade 1 or 2, 2.3%; grade 3, 0.6%).Conclusions: A single cilta-cel infusion resulted in a lower risk of disease progression or death than standard care in lenalidomide-refractory patients with multiple myeloma who had received one to three previous therapies. (Funded by Janssen and Legend Biotech; CARTITUDE-4 ClinicalTrials.gov number, NCT04181827.)

AB - Background: Ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen (BCMA)-directed CAR T-cell therapy, is effective in heavily pretreated patients with relapsed or refractory multiple myeloma. We investigated cilta-cel in earlier treatment lines in patients with lenalidomide-refractory disease.Methods: In this phase 3, randomized, open-label trial, we assigned patients with lenalidomide-refractory multiple myeloma to receive cilta-cel or the physician's choice of effective standard care. All the patients had received one to three previous lines of treatment. The primary outcome was progression-free survival.Results: A total of 419 patients underwent randomization (208 to receive cilta-cel and 211 to receive standard care). At a median follow-up of 15.9 months (range, 0.1 to 27.3), the median progression-free survival was not reached in the cilta-cel group and was 11.8 months in the standard-care group (hazard ratio, 0.26; 95% confidence interval [CI], 0.18 to 0.38; P<0.001). Progression-free survival at 12 months was 75.9% (95% CI, 69.4 to 81.1) in the cilta-cel group and 48.6% (95% CI, 41.5 to 55.3) in the standard-care group. More patients in the cilta-cel group than in the standard-care group had an overall response (84.6% vs. 67.3%), a complete response or better (73.1% vs. 21.8%), and an absence of minimal residual disease (60.6% vs. 15.6%). Death from any cause was reported in 39 patients and 46 patients, respectively (hazard ratio, 0.78; 95% CI, 0.5 to 1.2). Most patients reported grade 3 or 4 adverse events during treatment. Among the 176 patients who received cilta-cel in the as-treated population, 134 (76.1%) had cytokine release syndrome (grade 3 or 4, 1.1%; no grade 5), 8 (4.5%) had immune effector cell-associated neurotoxicity syndrome (all grade 1 or 2), 1 had movement and neurocognitive symptoms (grade 1), 16 (9.1%) had cranial nerve palsy (grade 2, 8.0%; grade 3, 1.1%), and 5 (2.8%) had CAR-T-related peripheral neuropathy (grade 1 or 2, 2.3%; grade 3, 0.6%).Conclusions: A single cilta-cel infusion resulted in a lower risk of disease progression or death than standard care in lenalidomide-refractory patients with multiple myeloma who had received one to three previous therapies. (Funded by Janssen and Legend Biotech; CARTITUDE-4 ClinicalTrials.gov number, NCT04181827.)

KW - Hematology/Oncology

KW - Leukemia/Lymphoma

KW - Treatments in Oncology

UR - http://www.scopus.com/inward/record.url?scp=85164409382&partnerID=8YFLogxK

U2 - 10.1056/NEJMoa2303379

DO - 10.1056/NEJMoa2303379

M3 - Article

AN - SCOPUS:85164409382

SN - 0028-4793

VL - 389

SP - 335

EP - 347

JO - New England Journal of Medicine

JF - New England Journal of Medicine

IS - 4

ER -

Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma

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